Spotlight on unmet needs in stroke prevention: The PIONEER AF-PCI, NAVIGATE ESUS and GALILEO trials.

PubMed

Hemmrich, Melanie; Peterson, Eric D; Thomitzek, Karen; Weitz, Jeffrey I

2016-09-28

Atrial fibrillation (AF) is a major healthcare concern, being associated with an estimated five-fold risk of ischaemic stroke. In patients with AF, anticoagulants reduce stroke risk to a greater extent than acetylsalicylic acid (ASA) or dual antiplatelet therapy (DAPT) with ASA plus clopidogrel. Non-vitamin K antagonist oral anticoagulants (NOACs) are now a widely-accepted therapeutic option for stroke prevention in non-valvular AF (NVAF). There are particular patient types with NVAF for whom treatment challenges remain, owing to sparse clinical data, their high-risk nature or a need to harmonise anticoagulant and antiplatelet regimens if co-administered. This article focuses on three randomised controlled trials (RCTs) that are investigating the utility of rivaroxaban, a direct, oral, factor Xa inhibitor, in additional areas of stroke prevention where data for anticoagulants are lacking: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment (PIONEER AF-PCI); New Approach riVaroxoban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS); and Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO). Data from these studies present collaborative efforts to build upon existing registrational Phase III data for rivaroxaban, driving the need for effective and safe treatment of a wider range of patients for stroke prevention.

XANTUS: rationale and design of a noninterventional study of rivaroxaban for the prevention of stroke in patients with atrial fibrillation

PubMed Central

Camm, A John; Amarenco, Pierre; Haas, Sylvia; Hess, Susanne; Kirchhof, Paulus; van Eickels, Martin; Turpie, Alexander GG

2014-01-01

Atrial fibrillation (AF) is associated with a fivefold increase in the risk of stroke. The Phase III ROCKET AF (Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial showed that rivaroxaban, an oral, direct Factor Xa inhibitor, was noninferior to warfarin for the reduction of stroke or systemic embolism in patients with AF. Compared with warfarin, rivaroxaban significantly reduced rates of intracranial and fatal hemorrhages, although not rates of bleeding overall. XANTUS (Xarelto® for Prevention of Stroke in Patients with Atrial Fibrillation) is a prospective, international, observational, postauthorization, noninterventional study designed to collect safety and efficacy data on the use of rivaroxaban for stroke prevention in AF in routine clinical practice. The key goal is to determine whether the safety profile of rivaroxaban established in ROCKET AF is also observed in routine clinical practice. XANTUS is designed as a single-arm cohort study to minimize selection bias, and will enroll approximately 6,000 patients (mostly from Europe) with nonvalvular AF prescribed rivaroxaban, irrespective of their level of stroke risk. Overall duration of follow-up will be 1 year; the first patient was enrolled in June 2012. Similar studies (XANTUS-EL [Xarelto® for Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation, Eastern Europe, Middle East, Africa and Latin America] and XANAP [Xarelto® for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific]) are ongoing in Latin America and Asia-Pacific. Data from these studies will supplement those from ROCKET AF and provide practical information concerning the use of rivaroxaban for stroke prevention in AF. PMID:25083135

Design of the stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis trial.

PubMed

Chimowitz, Marc I; Lynn, Michael J; Turan, Tanya N; Fiorella, David; Lane, Bethany F; Janis, Scott; Derdeyn, Colin P

2011-01-01

Patients with recent transient ischemic attack (TIA) or stroke caused by 70% to 99% stenosis of a major intracranial artery are at high risk of recurrent stroke on usual medical management, suggesting the need for alternative therapies for this disease. The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial is an ongoing, randomized, multicenter, 2-arm trial that will determine whether intracranial angioplasty and stenting adds benefit to aggressive medical management alone for preventing the primary endpoint (any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days) during a mean follow-up of 2 years in patients with recent TIA or stroke caused by 70% to 99% stenosis of a major intracranial artery. Aggressive medical management in both arms consists of aspirin 325 mg per day, clopidogrel 75 mg per day for 90 days after enrollment, intensive risk factor management primarily targeting systolic blood pressure <140 mm Hg (<130 mm Hg in diabetics) and low density cholesterol <70 mg/dL, and a lifestyle modification program. The sample size required to detect a 35% reduction in the rate of the primary endpoint from angioplasty and stenting based on the log-rank test with an alpha of 0.05, 80% power, and adjusting for a 2% loss to follow-up and 5% crossover from the medical to the stenting arm is 382 patients per group. Enrollment began in November 2008 and 451 patients have been enrolled as of March 31, 2011. This is the first randomized stroke prevention trial to compare angioplasty and stenting with medical therapy in patients with intracranial arterial stenosis and to incorporate intensive management of multiple risk factors and a lifestyle modification program in the study design. Hopefully, the results of the trial will lead to more effective therapy for this high-risk disease. Copyright © 2011 National Stroke Association. All rights reserved.

National trends in incidence rates of hospitalization for stroke in children with sickle cell disease.

PubMed

McCavit, Timothy L; Xuan, Lei; Zhang, Song; Flores, Glenn; Quinn, Charles T

2013-05-01

The success of primary stroke prevention for children with sickle cell disease (SCD) throughout the United States is unknown. Therefore, we aimed to generate national incidence rates of hospitalization for stroke in children with sickle cell disease (SCD) before and after publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998. We performed a retrospective trend analysis of the 1993-2009 Nationwide Inpatient Sample and Kids' Inpatient Databases. Hospitalizations for SCD patients 0-18 years old with stroke were identified by ICD-9CM code. The primary outcome, the trend in annual incidence rate of hospitalization for stroke in children with SCD, was analyzed by linear regression. Incidence rates of hospitalization for stroke before and after 1998 were compared by the Wilcoxon rank-sum test. From 1993 to 2009, 2,024 hospitalizations were identified for stroke. Using the mean annual incidence rate of hospitalization for stroke from 1993 to 1998 as the baseline, the rate decreased from 1993 to 2009 (point estimate = -0.022/100 patient years [95% CI, -0.039, -0.005], P = 0.027). The mean annual incidence rate of hospitalization stroke decreased by 45% from 0.51 per 100 patient years in 1993-1998 to 0.28 per 100 patient years in 1999-2009 (P = 0.008). Total hospital days and charges attributed to stroke also decreased by 45% and 24%, respectively. After publication of the STOP trial and hydroxyurea licensure in 1998, the incidence of hospitalization for stroke in children with SCD decreased across the United States, suggesting that primary stroke prevention has been effective nationwide, but opportunity for improvement remains. Copyright © 2012 Wiley Periodicals, Inc.

National Trends in Incidence Rates of Hospitalization for Stroke in Children With Sickle Cell Disease

PubMed Central

McCavit, Timothy L.; Xuan, Lei; Zhang, Song; Flores, Glenn; Quinn, Charles T.

2014-01-01

Background The success of primary stroke prevention for children with sickle cell disease (SCD) throughout the United States is unknown. Therefore, we aimed to generate national incidence rates of hospitalization for stroke in children with sickle cell disease (SCD) before and after publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998. Procedure We performed a retrospective trend analysis of the 1993–2009 Nationwide Inpatient Sample and Kids’ Inpatient Databases. Hospitalizations for SCD patients 0–18 years old with stroke were identified by ICD-9CM code. The primary outcome, the trend in annual incidence rate of hospitalization for stroke in children with SCD, was analyzed by linear regression. Incidence rates of hospitalization for stroke before and after 1998 were compared by the Wilcoxon rank-sum test. Results From 1993 to 2009, 2,024 hospitalizations were identified for stroke. Using the mean annual incidence rate of hospitalization for stroke from 1993 to 1998 as the baseline, the rate decreased from 1993 to 2009 (point estimate = −0.022/100 patient years [95% CI, −0.039, −0.005], P = 0.027). The mean annual incidence rate of hospitalization stroke decreased by 45% from 0.51 per 100 patient years in 1993–1998 to 0.28 per 100 patient years in 1999–2009 (P = 0.008). Total hospital days and charges attributed to stroke also decreased by 45% and 24%, respectively. Conclusions After publication of the STOP trial and hydroxyurea licensure in 1998, the incidence of hospitalization for stroke in children with SCD decreased across the United States, suggesting that primary stroke prevention has been effective nationwide, but opportunity for improvement remains. PMID:23151905

Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and a history of cryptogenic stroke or transient ischemic attack.

PubMed

Li, Jie; Liu, Junfeng; Liu, Ming; Zhang, Shihong; Hao, Zilong; Zhang, Jing; Zhang, Canfei

2015-09-08

The optimal therapy for preventing recurrent stroke in people with cryptogenic stroke and patent foramen ovale (PFO) has not been defined. The choice between medical therapy (antithrombotic treatment with antiplatelet agents or anticoagulants) and transcatheter device closure has been the subject of intense debate over the past several years. Despite the lack of scientific evidence, a substantial number of people undergo transcatheter device closure (TDC) for secondary stroke prevention. To: 1) compare the safety and efficacy of TDC with best medical therapy alone for preventing recurrent stroke (fatal or non-fatal) or transient ischemic attacks (TIAs) in people with PFO and a history of cryptogenic stroke or TIA; 2) identify specific subgroups of people most likely to benefit from closure for secondary prevention; and 3) assess the cost-effectiveness of this strategy, if possible. We searched the Cochrane Stroke Group Trials Register (July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2014), MEDLINE (1950 to July 2014) and EMBASE (1980 to July 2014). In an effort to identify unpublished and ongoing trials we searched seven trials registers and checked reference lists. We included randomized controlled trials (RCTs), irrespective of blinding, publication status, and language, comparing the safety and efficacy of device closure with medical therapy for preventing recurrent stroke or TIA in people with PFO and a history of cryptogenic stroke or TIA. Two review authors independently selected trials for inclusion, assessed quality and risk of bias, and extracted data. The primary outcome measures of this analysis were the composite endpoint of ischemic stroke or TIA events as well as recurrent fatal or non-fatal ischemic stroke. Secondary endpoints included all-cause mortality, serious adverse events (atrial fibrillation, myocardial infarction, bleeding) and procedural success and effective closure. We used the Mantel-Haenszel method to obtain pooled risk ratios (RRs) using the random-effects model regardless of the level of heterogeneity. We pooled data for the primary outcome measure with the generic inverse variance method using the random-effects model, yielding risk estimates as pooled hazard ratio (HR), which accounts for time-to-event outcomes. We included three RCTs involving a total of 2303 participants: 1150 participants were randomized to receive TDC and 1153 participants were randomized to receive medical therapy. Overall, the risk of bias was regarded as high. The mean follow-up period of all three included trials was less than five years. Baseline characteristics (age, sex, and vascular risk factors) were similar across trials. Intention-to-treat analyses did not show a statistically significant risk reduction in the composite endpoint of recurrent stroke or TIA in the TDC group when compared with medical therapy (RR 0.73, 95% CI 0.45 to 1.17). A time-to-event analysis combining the results of two RCTs also failed to show a significant risk reduction with TDC (HR 0.69, 95% CI 0.43 to 1.13). When assessing stroke prevention alone, TDC still did not show a statistically significant benefit (RR 0.61, 95% CI 0.29 to 1.27) (HR 0.55, 95% CI 0.26 to 1.18). In a sensitivity analysis including the two studies using the Amplatzer PFO occluder, TDC showed a possible protective effect on recurrent stroke compared with medical therapy (HR 0.38, 95% CI 0.14 to 1.02); however, it did not reach statistical significance. Safety analysis found that the overall risks for all-cause mortality and adverse events were similar in both the TDC and medical therapy groups. However, TDC increased the risk of new-onset atrial fibrillation (RR 3.50, 95% CI 1.47 to 8.35) and may be associated with the type of device used. The combined data from recent RCTs have shown no statistically significant differences between TDC and medical therapy in the prevention of recurrent ischemic stroke. TDC closure was associated with an increased risk of atrial fibrillation but not with serious adverse events.

Update of the Preventive Antibiotics in Stroke Study (PASS): statistical analysis plan.

PubMed

Westendorp, Willeke F; Vermeij, Jan-Dirk; Dippel, Diederik W J; Dijkgraaf, Marcel G W; van der Poll, Tom; Prins, Jan M; Vermeij, Frederique H; Roos, Yvo B W E M; Brouwer, Matthijs C; Zwinderman, Aeilko H; van de Beek, Diederik; Nederkoorn, Paul J

2014-10-01

Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were still blinded for all outcomes. The primary outcome is the score on the modified Rankin Scale (mRS), assessed by ordinal logistic regression analysis according to a proportional odds model. Secondary analysis of the primary outcome is the score on the mRS dichotomized as a favorable outcome (mRS 0 to 2) versus unfavorable outcome (mRS 3 to 6). Secondary outcome measures are death rate at discharge and 3 months, infection rate during hospital admission, length of hospital admission, volume of post-stroke care, use of antibiotics during hospital stay, quality-adjusted life years and costs. Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes. The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection and will be analyzed according to this pre-specified SAP. Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.

STROKE OUTCOMES AMONG PARTICIPANTS RANDOMIZED TO CHLORTHALIDONE, AMLODIPINE OR LISINOPRIL IN ALLHAT

PubMed Central

Yamal, José-Miguel; Oparil, Suzanne; Davis, Barry R.; Alderman, Michael H.; Calhoun, David A.; Cushman, William C.; Fendley, Herbert F.; Franklin, Stanley S.; Habib, Gabriel B.; Pressel, Sara L.; Probstfield, Jeffrey L.; Sastrasinh, Sithiporn

2014-01-01

Background The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. Methods and Results ALLHAT compared cardiovascular disease outcomes in participants initially treated with angiotensin-converting enzyme inhibitor (lisinopril), calcium channel blocker (amlodipine), or thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for total follow-up of 8–13 years. Stroke rates were higher with lisinopril (6-year rate/100=6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100=13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). In- trial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P=0.005, race-by-amlodipine/lisinopril interaction P=0.012) and gender (gender-by-lisinopril/amlodipine interaction P=0.041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Conclusions Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period. PMID:25455006

Apixaban to prevent stroke in patients with atrial fibrillation: a review

PubMed Central

Peterson, Benjamin E.; Al-Khatib, Sana M.; Granger, Christopher B.

2016-01-01

Atrial fibrillation is a common, costly and morbid cardiovascular arrhythmia. Stroke prevention remains the mainstay of treatment for atrial fibrillation, and the recent advent of novel oral anticoagulants with direct factor IIa or factor Xa inhibition has significantly revolutionized this aspect of treatment for atrial fibrillation patients. This review focuses on the tolerability and efficacy of apixaban and tackles the generalizability of the findings with apixaban to broader patient populations than those primarily enrolled in the clinical trials, drawing from the AVERROES and ARISTOTLE trials and their subsequent secondary analyses. Taken together, findings from these trials show that apixaban is superior to warfarin in preventing stroke with a lower risk of major bleeding in the general population of patients with atrial fibrillation as well as in several key high-risk patient subgroups. PMID:27342651

Interventions for preventing silent cerebral infarcts in people with sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Doree, Carolyn; Abboud, Miguel R

2017-01-01

Background Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Silent cerebral infarcts are the commonest neurological complication in children and probably adults with SCD. Silent cerebral infarcts also affect academic performance, increase cognitive deficits and may lower intelligence quotient. Objectives To assess the effectiveness of interventions to reduce or prevent silent cerebral infarcts in people with SCD. Search methods We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 19 September 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 06 October 2016. Selection criteria Randomised controlled trials comparing interventions to prevent silent cerebral infarcts in people with SCD. There were no restrictions by outcomes examined, language or publication status. Data collection and analysis We used standard Cochrane methodological procedures. Main results We included five trials (660 children or adolescents) published between 1998 and 2016. Four of the five trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of SCD. One trial focused on preventing silent cerebral infarcts or stroke; three trials were for primary stroke prevention and one trial dealt with secondary stroke prevention. Three trials compared the use of regular long-term red blood cell transfusions to standard care. Two of these trials included children with no previous long-term transfusions: one in children with normal transcranial doppler (TCD) velocities; and one in children with abnormal TCD velocities. The third trial included children and adolescents on long-term transfusion. Two trials compared the drug hydroxyurea and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children), and one in secondary prevention (children and adolescents). The quality of the evidence was moderate to very low across different outcomes according to GRADE methodology. This was due to trials being at high risk of bias because they were unblinded; indirectness (available evidence was only for children with HbSS); and imprecise outcome estimates. Long-term red blood cell transfusions versus standard care Children with no previous long-term transfusions and higher risk of stroke (abnormal TCD velocities or previous history of silent cerebral infarcts) Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, risk ratio (RR) 0.11 (95% confidence interval (CI) 0.02 to 0.86) (one trial, 124 participants, low-quality evidence); but make little or no difference to the incidence of silent cerebral infarcts in children with previous silent cerebral infarcts on magnetic resonance imaging and normal or conditional TCDs, RR 0.70 (95% CI 0.23 to 2.13) (one trial, 196 participants, low-quality evidence). No deaths were reported in either trial. Long-term red blood cell transfusions may reduce the incidence of: acute chest syndrome, RR 0.24 (95% CI 0.12 to 0.49) (two trials, 326 participants, low-quality evidence); and painful crisis, RR 0.63 (95% CI 0.42 to 0.95) (two trials, 326 participants, low-quality evidence); and probably reduces the incidence of clinical stroke, RR 0.12 (95% CI 0.03 to 0.49) (two trials, 326 participants, moderate-quality evidence). Long-term red blood cell transfusions may improve quality of life in children with previous silent cerebral infarcts (difference estimate -0.54; 95% confidence interval -0.92 to -0.17; one trial; 166 participants), but may have no effect on cognitive function (least squares means: 1.7, 95% CI -1.1 to 4.4) (one trial, 166 participants, low-quality evidence). Transfusions continued versus transfusions halted: children and adolescents with normalised TCD velocities (79 participants; one trial) Continuing red blood cell transfusions may reduce the incidence of silent cerebral infarcts, RR 0.29 (95% CI 0.09 to 0.97 (low-quality evidence). We are very uncertain whether continuing red blood cell transfusions has any effect on all-cause mortality, Peto odds ratio (OR) 8.00 (95% CI 0.16 to 404.12); or clinical stroke, RR 0.22 (95% CI 0.01 to 4.35) (very low-quality evidence). The trial did not report: comparative numbers for SCD-related adverse events; quality of life; or cognitive function. Hydroxyurea and phlebotomy versus transfusions and chelation Primary prevention, children (121 participants; one trial) We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts (no infarcts); all-cause mortality (no deaths); risk of stroke (no strokes); or SCD-related complications, RR 1.52 (95% CI 0.58 to 4.02) (very low-quality evidence). Secondary prevention, children and adolescents with a history of stroke (133 participants; one trial) We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts, Peto OR 7.28 (95% CI 0.14 to 366.91); all-cause mortality, Peto OR 1.02 (95% CI 0.06 to 16.41); or clinical stroke, RR 14.78 (95% CI 0.86 to 253.66) (very low-quality evidence). Switching to hydroxyurea and phlebotomy may increase the risk of SCD-related complications, RR 3.10 (95% CI 1.42 to 6.75) (low-quality evidence). Neither trial reported on quality of life or cognitive function. Authors’ conclusions We identified no trials for preventing silent cerebral infarcts in adults, or in children who do not have HbSS SCD. Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, but may have little or no effect on children with normal TCD velocities. In children who are at higher risk of stroke and have not had previous long-term transfusions, long-term red blood cell transfusions probably reduce the risk of stroke, and other SCD-related complications (acute chest syndrome and painful crises). In children and adolescents at high risk of stroke whose TCD velocities have normalised, continuing red blood cell transfusions may reduce the risk of silent cerebral infarcts. No treatment duration threshold has been established for stopping transfusions. Switching to hydroxyurea with phlebotomy may increase the risk of silent cerebral infarcts and SCD-related serious adverse events in secondary stroke prevention. All other evidence in this review is of very low-quality. PMID:28500860

Patent foramen ovale closure and medical treatments for secondary stroke prevention: a systematic review of observational and randomized evidence.

PubMed

Kitsios, Georgios D; Dahabreh, Issa J; Abu Dabrh, Abd Moain; Thaler, David E; Kent, David M

2012-02-01

Patients discovered to have a patent foramen ovale in the setting of a cryptogenic stroke may be treated with percutaneous closure, antiplatelet therapy, or anticoagulants. A recent randomized trial (CLOSURE I) did not detect any benefit of closure over medical treatment alone; the optimal medical therapy is also unknown. We synthesized the available evidence on secondary stroke prevention in patients with patent foramen ovale and cryptogenic stroke. A MEDLINE search was performed for finding longitudinal studies investigating medical treatment or closure, meta-analysis of incidence rates (IR), and IR ratios of recurrent cerebrovascular events. Fifty-two single-arm studies and 7 comparative nonrandomized studies and the CLOSURE I trial were reviewed. The summary IR of recurrent stroke was 0.36 events (95% confidence interval [CI], 0.24-0.56) per 100 person-years with closure versus 2.53 events (95% CI, 1.91-3.35) per 100 person-years with medical therapy. In comparative observational studies, closure was superior to medical therapy (IR ratio=0.19; 95% CI, 0.07-0.54). The IR for the closure arm of the CLOSURE I trial was higher than the summary estimate from observational studies; there was no significant benefit of closure over medical treatment (P=0.002 comparing efficacy estimates between observational studies and the trial). Observational and randomized data (9 studies) comparing medical therapies were consistent and suggested that anticoagulants are superior to antiplatelets for preventing stroke recurrence (IR ratio=0.42; 95% CI, 0.18-0.98). Although further randomized trial data are needed to precisely determine the effects of closure on stroke recurrence, the results of CLOSURE I challenge the credibility of a substantial body of observational evidence strongly favoring mechanical closure over medical therapy.

Chuanxiong preparations for preventing stroke.

PubMed

Yang, Xunzhe; Zeng, Xiaoxi; Wu, Taixiang

2010-01-20

Stroke is a major healthcare problem and is one of the leading causes of death and serious long-term disability. Prevention of stroke is considered an important strategy. Chuanxiong is traditionally used in China in the treatment and prevention of stroke. In recent years, Chinese researchers have developed new patented Chuanxiong preparations. To assess the effects and safety of Chuanxiong preparations in preventing stroke in high-risk adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2008, Issue 1), MEDLINE (1950 to March 2008), EMBASE (1980 to March 2008), AMED (1985 to March 2008), Chinese Biomedical Database (CBM) (1975 to March 2008), China National Knowledge Infrastructure (CNKI) (1994 to March 2008), and the VIP Database (1989 to March 2008). Trials registers were searched for ongoing studies. No language restrictions were applied. Randomised controlled trials (RCTs) studying the effects of Chuanxiong preparations in preventing stroke were included. Three reviewers independently selected studies for inclusion and two reviewers independently extracted data. Authors of identified RCTs were telephoned to confirm the randomisation procedure. Outcomes assessed included: stroke, composite cardiovascular outcomes, changes in cardiovascular and cerebrovascular haemodynamic indices and adverse events. Peto odds ratio (OR) with 95% confidence intervals (CI) were calculated for dichotomous variables and mean differences for continuous outcomes. Three RCTs (5042 participants) were included. One higher quality study (4415 participants) compared Nao-an capsule with aspirin for primary prevention in high-risk stroke populations. Nao-an capsule appeared to reduce the incidence of stroke compared with aspirin (OR 0.56 95% CI 0.33 to 0.96). One study of low methodological quality indicated that a self-prepared Xifenwan tablet reduced the incidence of stroke in people with transient ischaemia attack (TIA) (OR 0.18, 95% CI 0.04 to 0.78). The remaining low quality study indicated that "apoplexy 2 preventing dry ointment powder" appeared to reduce both fatal stroke and incidence of stroke (OR 0.21, 95% CI 0.10 to 0.43, and OR 0.28, 95% CI 0.16 to 0.49, respectively). Nao-an capsule may be a choice for the primary prevention of stroke. However, the design of the study providing this evidence means that there was potential for results to have been affected by bias from the way participants may have been selected, or from investigators' conflicts of interests. There was a lack of description of the methodology in the two other studies therefore evidence from these was considered too weak to draw any firm conclusions. Further high quality research is required.

Stroke prevention in atrial fibrillation: pooled analysis of SPORTIF III and V trials.

PubMed

Albers, Gregory W

2004-12-01

This article will review 2 clinical trials that recently compared the safety and efficacy of the oral direct thrombin inhibitor ximelagatran (fixed dose, 36 mg twice daily) with warfarin (adjusted dose, target international normalized ratio [INR] 2.0-3.0) in patients with nonvalvular atrial fibrillation and at least 1 risk factor for stroke. These noninferiority trials involved 7329 patients and a mean exposure to study drug of 18.5 months. The Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III (open-label, N = 3407) and V trials (double-blind, N = 3922) were designed for pooled analysis, and the data showed the efficacy of ximelagatran therapy was comparable (noninferior) with extremely well-controlled warfarin therapy in preventing stroke and systemic embolic events; the primary event rates were 1.65% per year and 1.62% per year in the warfarin and ximelagatran groups, respectively (P = .941). In patients with a history of stroke or transient ischemic attack (about 20% of the SPORTIF population), the event rates were 3.27% per year and 2.83% per year in the warfarin and ximelagatran groups, respectively (P = .625). The distribution of stroke subtypes was similar in the 2 treatment groups. Intracranial hemorrhage occurred at a rate of 0.20% per year with warfarin and 0.11% per year with ximelagatran. Combined rates of minor and major bleeding were significantly lower with ximelagatran than with warfarin (32% per year vs 39% per year; P < .0001). The myocardial infarction rates were the same in the pooled database (no difference between agents). The aspirin data will be the subject of two substudy papers. Oral ximelagatran administered without coagulation monitoring or dose adjustment was as effective as well-controlled, adjusted-dose warfarin for prevention of stroke and systemic embolic events and was associated with significantly less total bleeding. This oral direct thrombin inhibitor is a potentially promising treatment option for the prevention of thromboembolism.

Recommendations for Management of Patients with Carotid Stenosis

PubMed Central

Lovrencic-Huzjan, Arijana; Rundek, Tatjana; Katsnelson, Michael

2012-01-01

Stroke is a one of the leading causes of morbidity and mortality in the world. Carotid atherosclerosis is recognized as an important factor in stroke pathophysiology and represents a key target in stroke prevention; multiple treatment modalities have been developed to battle this disease. Multiple randomized trials have shown the efficacy of carotid endarterectomy in secondary stroke prevention. Carotid stenting, a newer treatment option, presents a less invasive alternative to the surgical intervention on carotid arteries. Advances in medical therapy have also enabled further risk reduction in the overall incidence of stroke. Despite numerous trials and decades of clinical research, the optimal management of symptomatic and asymptomatic carotid disease remains controversial. We will attempt to highlight some of the pivotal trials already completed, discuss the current controversies and complexities in the treatment decision-making, and postulate on what likely lies ahead. This paper will highlight the complexities of decision-making optimal treatment recommendations for patients with symptomatic and asymptomatic carotid stenosis. PMID:22645702

Cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation in the primary prevention of ischemic stroke.

PubMed

Lightowlers, S; McGuire, A

1998-09-01

A number of clinical trials have shown the value of anticoagulating patients with nonrheumatic atrial fibrillation to prevent ischemic stroke. The purpose of this study was to assess the cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation with particular reference to the very elderly (aged >75 years) who have a higher incidence of bleeding events while undergoing anticoagulation. We calculated the incremental costs per life-year gained for 4 base cases using efficacy data from the Boston Area Anticoagulation Trial for Atrial Fibrillation, the meta-analysis of the 5 nonrheumatic atrial fibrillation trials, cost data from a district general hospital, and review of the literature. The cost per life-year gained free from stroke over 10 years ranged from -pound sterling 400.45 (ie, a resource saving achieved for each life-year gained free from stroke) to pound sterling 13,221.29. The results were most sensitive to alteration in the frequency of anticoagulation monitoring. For medical and economic reasons, anticoagulation treatment in the prevention of ischemic stroke is justified. Although older patients are more at risk of adverse events, anticoagulation is more cost-effective in this group.

Antibiotic therapy for preventing infections in people with acute stroke.

PubMed

Vermeij, Jan-Dirk; Westendorp, Willeke F; Dippel, Diederik Wj; van de Beek, Diederik; Nederkoorn, Paul J

2018-01-22

Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome. In the previous version of this Cochrane Review, published in 2012, we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients. However, included studies were small and heterogeneous. In 2015, two large clinical trials were published, warranting an update of this Review. To assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We wished to determine whether preventive antibiotic therapy in people with acute stroke:• reduces the risk of a poor functional outcome (dependency and/or death) at follow-up;• reduces the occurrence of infections in the acute phase of stroke;• reduces the occurrence of elevated body temperature (temperature ≥ 38° C) in the acute phase of stroke;• reduces length of hospital stay; or• leads to an increased rate of serious adverse events, such as anaphylactic shock, skin rash, or colonisation with antibiotic-resistant micro-organisms. We searched the Cochrane Stroke Group Trials Register (25 June 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25 June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and Embase Ovid (1980 to 11 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched trials and research registers, scanned reference lists, and contacted trial authors, colleagues, and researchers in the field. Randomised controlled trials (RCTs) of preventive antibiotic therapy versus control (placebo or open control) in people with acute ischaemic or haemorrhagic stroke. Two review authors independently selected articles and extracted data; we discussed and resolved discrepancies at a consensus meeting with a third review author. We contacted study authors to obtain missing data when required. An independent review author assessed risk of bias using the Cochrane 'Risk of bias' tool. We calculated risk ratios (RRs) for dichotomous outcomes, assessed heterogeneity amongst included studies, and performed subgroup analyses on study quality. We included eight studies involving 4488 participants. Regarding quality of evidence, trials showed differences in study population, study design, type of antibiotic, and definition of infection; however, primary outcomes among the included studies were consistent. Mortality rate in the preventive antibiotic group was not significantly different from that in the control group (373/2208 (17%) vs 360/2214 (16%); RR 1.03, 95% confidence interval (CI) 0.87 to 1.21; high-quality evidence). The number of participants with a poor functional outcome (death or dependency) in the preventive antibiotic therapy group was also not significantly different from that in the control group (1158/2168 (53%) vs 1182/2164 (55%); RR 0.99, 95% CI 0.89 to 1.10; moderate-quality evidence). However, preventive antibiotic therapy did significantly reduce the incidence of 'overall' infections in participants with acute stroke from 26% to 19% (408/2161 (19%) vs 558/2156 (26%); RR 0.71, 95% CI 0.58 to 0.88; high-quality evidence). This finding was highly significant for urinary tract infections (81/2131 (4%) vs 204/2126 (10%); RR 0.40, 95% CI 0.32 to 0.51; high-quality evidence), whereas no preventive effect for pneumonia was found (222/2131 (10%) vs 235/2126 (11%); RR 0.95, 95% CI 0.80 to 1.13; high-quality evidence). No major side effects of preventive antibiotic therapy were reported. Only two studies qualitatively assessed the occurrence of elevated body temperature; therefore, these results could not be pooled. Only one study reported length of hospital stay. Preventive antibiotics had no effect on functional outcome or mortality, but significantly reduced the risk of 'overall' infections. This reduction was driven mainly by prevention of urinary tract infection; no effect for pneumonia was found.

Prevention of cardiovascular events in elderly people.

PubMed

Andrawes, Wafik Farah; Bussy, Caroline; Belmin, Joël

2005-01-01

Cardiovascular disease has been identified as the leading cause of morbidity and mortality in developed countries. Given the increase in life expectancy and the development of cardiovascular preventive measures, it has become increasingly important to detect and prevent cardiovascular diseases in the elderly. We reviewed the scientific literature concerning cardiovascular prevention to assess the importance of cardiovascular preventive measures in old (> or =65 years of age) individuals. We undertook a systematic search for references relating to prevention of cardiovascular disease in the elderly, mainly ischaemic stroke, coronary artery disease and heart failure, on the MEDLINE database 1962-2005. For cardiovascular prevention by drugs or surgery, emphasis was placed on randomised controlled trials, review articles and meta-analyses. For cardiovascular prevention by lifestyle modification, major cohort studies were also considered. Stroke, coronary heart disease and heart failure were found to be the main targets for cardiovascular prevention in published studies. Antihypertensive treatment has proven its efficacy in primary prevention of fatal or nonfatal stroke in hypertensive and high-risk patients >60 years of age, particularly through treatment of systolic hypertension. Systolic blood pressure reduction is equally important in the secondary prevention of stroke. Similarly, in nonvalvular atrial fibrillation, an adjusted dose of warfarin with a target International Normalized Ratio (INR) of between 2 to 3 prevents ischaemic stroke in elderly patients with an acceptable haemorrhagic risk but is still under prescribed. Antiplatelet agents are indicated in elderly patients with nonembolic strokes. Few large-scale studies have investigated the effect of HMG-CoA reductase inhibitors (statins) on stroke prevention in old individuals. To date, the largest trials suggest a beneficial effect for stroke prevention with use of statins in high-risk elderly subjects < or =82 years of age. Carotid endarterectomy is indicated in carotid artery stenosis >70% and outcomes are even better in elderly than in younger patients. However, medical treatment is still the first-line treatment in asymptomatic elderly patients with <70% stenosis. In ischaemic heart disease, different trials in elderly individuals have shown that use of statins, antithrombotic agents, beta-adrenoceptor antagonists and ACE inhibitors plays an important role either in primary or in secondary cardiovascular prevention. Hormone replacement therapy has been used to treat climacteric symptoms and postmenopausal osteoporosis and was thought to confer a cardiovascular protection. However, controlled trials in elderly individuals changed this false belief when it was found that there was no benefit and even a harmful cardiovascular effect during the first year of treatment. Smoking cessation, regular physical activity and healthy diet are, as in younger individuals, appropriate and effective measures for preventing cardiovascular events in the elderly. Finally, antihypertensive treatment and influenza vaccination are useful for heart failure prevention in elderly individuals. Cardiovascular prevention should be more widely implemented in the elderly, including individuals aged > or =75 years, and this might contribute to improved healthy status and quality of life in this growing population.

Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial.

PubMed

Wong, Ka Sing Lawrence; Hu, Dai Yi; Oomman, Abraham; Tan, Ru-San; Patel, Manesh R; Singer, Daniel E; Breithardt, Günter; Mahaffey, Kenneth W; Becker, Richard C; Califf, Robert; Fox, Keith A A; Berkowitz, Scott D; Hacke, Werner; Hankey, Graeme J

2014-06-01

In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk. Because of differences in patient demographics, epidemiology, and stroke risk management in East Asia, outcomes and relative effects of rivaroxaban versus warfarin were assessed to determine consistency among East Asians versus other ROCKET AF participants. Baseline demographics and interaction of treatment effects of rivaroxaban and warfarin among patients within East Asia and outside were assessed. A total of 932 (6.5%) ROCKET AF participants resided in East Asia. At baseline, East Asians had lower weight, creatinine clearance, and prior vitamin K antagonist use; higher prevalence of prior stroke; and less congestive heart failure and prior myocardial infarction than other participants. Despite higher absolute event rates for efficacy and safety outcomes in East Asians, the relative efficacy of rivaroxaban (20 mg once daily; 15 mg once daily for creatinine clearance of 30-49 mL/min) versus warfarin with respect to the primary efficacy end point (stroke/systemic embolism) was consistent among East Asians and non-East Asians (interaction P=0.666). Relative event rates for the major or nonmajor clinically relevant bleeding in patients treated with rivaroxaban and warfarin were consistent among East Asians and non-East Asians (interaction P=0.867). Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. Rivaroxaban, 20 mg once daily, is an alternative to warfarin for stroke prevention in East Asians with nonvalvular atrial fibrillation. © 2014 American Heart Association, Inc.

Challenges of stroke prevention in patients with atrial fibrillation in clinical practice.

PubMed

Hobbs, F D Richard; Leach, I

2011-09-01

Strokes and transient ischaemic attacks in patients with atrial fibrillation (AF) can be largely prevented. Risk stratification and appropriate prophylactic regimens help to alleviate the burden of AF-related thromboembolism. Guidelines recommend routine anticoagulation with oral vitamin K antagonists (VKAs) for patients at moderate-to-high risk of stroke, and acetylsalicylic acid (ASA) for those at low risk of stroke. ASA is less effective at reducing the risk of stroke than VKAs; however, ASA does not require monitoring or dose adjustment. Trials of anticoagulants show consistent benefits of oral VKAs for primary and secondary stroke prevention in patients with AF. Nevertheless, VKAs do require frequent coagulation monitoring and dose adjustment because of their variable dose-response profile, narrow therapeutic window, increased risk for bleeding complications and numerous food and drug interactions. This review aims to provide an overview of the clinical challenges of anticoagulant therapy for the prevention of stroke in patients with AF.

Relationship between risk factor control and vascular events in the SAMMPRIS trial

PubMed Central

Nizam, Azhar; Lynn, Michael J.; Egan, Brent M.; Le, Ngoc-Anh; Lopes-Virella, Maria F.; Hermayer, Kathie L.; Harrell, Jamie; Derdeyn, Colin P.; Fiorella, David; Janis, L. Scott; Lane, Bethany; Montgomery, Jean; Chimowitz, Marc I.

2017-01-01

Objective: The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study is the first stroke prevention trial to include protocol-driven intensive management of multiple risk factors. In this prespecified analysis, we aimed to investigate the relationship between risk factor control during follow-up and outcome of patients in the medical arm of SAMMPRIS. Methods: Data from SAMMPRIS participants in the medical arm (n = 227) were analyzed. Risk factors were recorded at baseline, 30 days, 4 months, and then every 4 months for a mean follow-up of 32 months. For each patient, values for all risk factor measures were averaged and dichotomized as in or out of target. Results: Participants who were out of target for systolic blood pressure and physical activity, as well as those with higher mean low-density lipoprotein cholesterol and non–high-density lipoprotein, were more likely to have a recurrent vascular event (stroke, myocardial infarction, or vascular death) at 3 years compared to those who had good risk factor control. In the multivariable analysis, greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death (odds ratio 0.6, confidence interval 0.4–0.8). Conclusions: Raised blood pressure, cholesterol, and physical inactivity should be aggressively treated in patients with intracranial atherosclerosis to prevent future vascular events. Physical activity, which has not received attention in stroke prevention trials, was the strongest predictor of a good outcome in the medical arm in SAMMPRIS. ClinicalTrials.gov identifier: NCT00576693. PMID:28003500

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease.

PubMed

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Wang, Winfred C

2017-01-17

Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation.This is an update of a Cochrane Review first published in 2002, and last updated in 2013. To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease for primary and secondary stroke prevention (excluding silent cerebral infarcts). We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 04 April 2016.We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 25 April 2016. Randomised controlled trials comparing red blood cell transfusions as prophylaxis for stroke in people with sickle cell disease to alternative or standard treatment. There were no restrictions by outcomes examined, language or publication status. Two authors independently assessed trial eligibility and the risk of bias and extracted data. We included five trials (660 participants) published between 1998 and 2016. Four of these trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of sickle cell disease.Three trials compared regular red cell transfusions to standard care in primary prevention of stroke: two in children with no previous long-term transfusions; and one in children and adolescents on long-term transfusion.Two trials compared the drug hydroxyurea (hydroxycarbamide) and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children); and one in secondary prevention (children and adolescents).The quality of the evidence was very low to moderate across different outcomes according to GRADE methodology. This was due to the trials being at a high risk of bias due to lack of blinding, indirectness and imprecise outcome estimates. Red cell transfusions versus standard care Children with no previous long-term transfusionsLong-term transfusions probably reduce the incidence of clinical stroke in children with a higher risk of stroke (abnormal transcranial doppler velocities or previous history of silent cerebral infarct), risk ratio 0.12 (95% confidence interval 0.03 to 0.49) (two trials, 326 participants), moderate quality evidence.Long-term transfusions may: reduce the incidence of other sickle cell disease-related complications (acute chest syndrome, risk ratio 0.24 (95% confidence interval 0.12 to 0.48)) (two trials, 326 participants); increase quality of life (difference estimate -0.54, 95% confidence interval -0.92 to -0.17) (one trial, 166 participants); but make little or no difference to IQ scores (least square mean: 1.7, standard error 95% confidence interval -1.1 to 4.4) (one trial, 166 participants), low quality evidence.We are very uncertain whether long-term transfusions: reduce the risk of transient ischaemic attacks, Peto odds ratio 0.13 (95% confidence interval 0.01 to 2.11) (two trials, 323 participants); have any effect on all-cause mortality, no deaths reported (two trials, 326 participants); or increase the risk of alloimmunisation, risk ratio 3.16 (95% confidence interval 0.18 to 57.17) (one trial, 121 participants), very low quality evidence. Children and adolescents with previous long-term transfusions (one trial, 79 participants)We are very uncertain whether continuing long-term transfusions reduces the incidence of: stroke, risk ratio 0.22 (95% confidence interval 0.01 to 4.35); or all-cause mortality, Peto odds ratio 8.00 (95% confidence interval 0.16 to 404.12), very low quality evidence.Several review outcomes were only reported in one trial arm (sickle cell disease-related complications, alloimmunisation, transient ischaemic attacks).The trial did not report neurological impairment, or quality of life. Hydroxyurea and phlebotomy versus red cell transfusions and chelationNeither trial reported on neurological impairment, alloimmunisation, or quality of life. Primary prevention, children (one trial, 121 participants)Switching to hydroxyurea and phlebotomy may have little or no effect on liver iron concentrations, mean difference -1.80 mg Fe/g dry-weight liver (95% confidence interval -5.16 to 1.56), low quality evidence.We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: risk of stroke (no strokes); all-cause mortality (no deaths); transient ischaemic attacks, risk ratio 1.02 (95% confidence interval 0.21 to 4.84); or other sickle cell disease-related complications (acute chest syndrome, risk ratio 2.03 (95% confidence interval 0.39 to 10.69)), very low quality evidence. Secondary prevention, children and adolescents (one trial, 133 participants)Switching to hydroxyurea and phlebotomy may: increase the risk of sickle cell disease-related serious adverse events, risk ratio 3.10 (95% confidence interval 1.42 to 6.75); but have little or no effect on median liver iron concentrations (hydroxyurea, 17.3 mg Fe/g dry-weight liver (interquartile range 10.0 to 30.6)); transfusion 17.3 mg Fe/g dry-weight liver (interquartile range 8.8 to 30.7), low quality evidence.We are very uncertain whether switching to hydroxyurea and phlebotomy: increases the risk of stroke, risk ratio 14.78 (95% confidence interval 0.86 to 253.66); or has any effect on all-cause mortality, Peto odds ratio 0.98 (95% confidence interval 0.06 to 15.92); or transient ischaemic attacks, risk ratio 0.66 (95% confidence interval 0.25 to 1.74), very low quality evidence. There is no evidence for managing adults, or children who do not have HbSS sickle cell disease.In children who are at higher risk of stroke and have not had previous long-term transfusions, there is moderate quality evidence that long-term red cell transfusions reduce the risk of stroke, and low quality evidence they also reduce the risk of other sickle cell disease-related complications.In primary and secondary prevention of stroke there is low quality evidence that switching to hydroxyurea with phlebotomy has little or no effect on the liver iron concentration.In secondary prevention of stroke there is low-quality evidence that switching to hydroxyurea with phlebotomy increases the risk of sickle cell disease-related events.All other evidence in this review is of very low quality.

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Wang, Winfred C

2017-01-01

Background Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation. This is an update of a Cochrane Review first published in 2002, and last updated in 2013. Objectives To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease for primary and secondary stroke prevention (excluding silent cerebral infarcts). Search methods We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 04 April 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 25 April 2016. Selection criteria Randomised controlled trials comparing red blood cell transfusions as prophylaxis for stroke in people with sickle cell disease to alternative or standard treatment. There were no restrictions by outcomes examined, language or publication status. Data collection and analysis Two authors independently assessed trial eligibility and the risk of bias and extracted data. Main results We included five trials (660 participants) published between 1998 and 2016. Four of these trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of sickle cell disease. Three trials compared regular red cell transfusions to standard care in primary prevention of stroke: two in children with no previous long-term transfusions; and one in children and adolescents on long-term transfusion. Two trials compared the drug hydroxyurea (hydroxycarbamide) and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children); and one in secondary prevention (children and adolescents). The quality of the evidence was very low to moderate across different outcomes according to GRADE methodology. This was due to the trials being at a high risk of bias due to lack of blinding, indirectness and imprecise outcome estimates. Red cell transfusions versus standard care Children with no previous long-term transfusions Long-term transfusions probably reduce the incidence of clinical stroke in children with a higher risk of stroke (abnormal transcranial doppler velocities or previous history of silent cerebral infarct), risk ratio 0.12 (95% confidence interval 0.03 to 0.49) (two trials, 326 participants), moderate quality evidence. Long-term transfusions may: reduce the incidence of other sickle cell disease-related complications (acute chest syndrome, risk ratio 0.24 (95% confidence interval 0.12 to 0.48)) (two trials, 326 participants); increase quality of life (difference estimate -0.54, 95% confidence interval -0.92 to -0.17) (one trial, 166 participants); but make little or no difference to IQ scores (least square mean: 1.7, standard error 95% confidence interval -1.1 to 4.4) (one trial, 166 participants), low quality evidence. We are very uncertain whether long-term transfusions: reduce the risk of transient ischaemic attacks, Peto odds ratio 0.13 (95% confidence interval 0.01 to 2.11) (two trials, 323 participants); have any effect on all-cause mortality, no deaths reported (two trials, 326 participants); or increase the risk of alloimmunisation, risk ratio 3.16 (95% confidence interval 0.18 to 57.17) (one trial, 121 participants), very low quality evidence. Children and adolescents with previous long-term transfusions (one trial, 79 participants) We are very uncertain whether continuing long-term transfusions reduces the incidence of: stroke, risk ratio 0.22 (95% confidence interval 0.01 to 4.35); or all-cause mortality, Peto odds ratio 8.00 (95% confidence interval 0.16 to 404.12), very low quality evidence. Several review outcomes were only reported in one trial arm (sickle cell disease-related complications, alloimmunisation, transient ischaemic attacks). The trial did not report neurological impairment, or quality of life. Hydroxyurea and phlebotomy versus red cell transfusions and chelation Neither trial reported on neurological impairment, alloimmunisation, or quality of life. Primary prevention, children (one trial, 121 participants) Switching to hydroxyurea and phlebotomy may have little or no effect on liver iron concentrations, mean difference -1.80 mg Fe/g dry-weight liver (95% confidence interval -5.16 to 1.56), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: risk of stroke (no strokes); all-cause mortality (no deaths); transient ischaemic attacks, risk ratio 1.02 (95% confidence interval 0.21 to 4.84); or other sickle cell disease-related complications (acute chest syndrome, risk ratio 2.03 (95% confidence interval 0.39 to 10.69)), very low quality evidence. Secondary prevention, children and adolescents (one trial, 133 participants) Switching to hydroxyurea and phlebotomy may: increase the risk of sickle cell disease-related serious adverse events, risk ratio 3.10 (95% confidence interval 1.42 to 6.75); but have little or no effect on median liver iron concentrations (hydroxyurea, 17.3 mg Fe/g dry-weight liver (interquartile range 10.0 to 30.6)); transfusion 17.3 mg Fe/g dry-weight liver (interquartile range 8.8 to 30.7), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy: increases the risk of stroke, risk ratio 14.78 (95% confidence interval 0.86 to 253.66); or has any effect on all-cause mortality, Peto odds ratio 0.98 (95% confidence interval 0.06 to 15.92); or transient ischaemic attacks, risk ratio 0.66 (95% confidence interval 0.25 to 1.74), very low quality evidence. Authors’ conclusions There is no evidence for managing adults, or children who do not have HbSS sickle cell disease. In children who are at higher risk of stroke and have not had previous long-term transfusions, there is moderate quality evidence that long-term red cell transfusions reduce the risk of stroke, and low quality evidence they also reduce the risk of other sickle cell disease-related complications. In primary and secondary prevention of stroke there is low quality evidence that switching to hydroxyurea with phlebotomy has little or no effect on the liver iron concentration. In secondary prevention of stroke there is low-quality evidence that switching to hydroxyurea with phlebotomy increases the risk of sickle cell disease-related events. All other evidence in this review is of very low quality. PMID:24226646

Role of rivaroxaban in the management of atrial fibrillation: insights from clinical practice.

PubMed

Vimalesvaran, Kavitha; Dockrill, Seth J; Gorog, Diana A

2018-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and it leads to significant morbidity and mortality, predominantly from ischemic stroke. Vitamin K antagonists, mainly warfarin, have been used for decades to prevent ischemic stroke in AF, but their use is limited due to interactions with food and other drugs, as well as the requirement for regular monitoring of the international normalized ratio. Rivaroxaban, a direct factor Xa inhibitor and the most commonly used non-vitamin K oral anticoagulant, avoids many of these challenges and is being prescribed with increasing frequency for stroke prevention in non-valvular AF. Randomized controlled trial (RCT) data from the ROCKET-AF(Rivaroxaban once daily oral direct Factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation) trial have shown rivaroxaban to be non-inferior to warfarin in preventing ischemic stroke and systemic embolism and to have comparable overall bleeding rates. Applicability of the RCT data to real-world practice can sometimes be limited by complex clinical scenarios or multiple comorbidities not adequately represented in the trials. Available real-world evidence in non-valvular AF patients with comorbidities - including renal impairment, acute coronary syndrome, diabetes mellitus, malignancy, or old age - supports the use of rivaroxaban as safe and effective in preventing ischemic stroke in these subgroups, though with some important considerations required to reduce bleeding risk. Patient perspectives on rivaroxaban use are also considered. Real-world evidence indicates superior rates of drug adherence with rivaroxaban when compared with vitamin K antagonists and with alternative non-vitamin K oral anticoagulants - perhaps, in part, due to its once-daily dosing regimen. Furthermore, self-reported quality of life scores are highest among patients compliant with rivaroxaban therapy. The generally high levels of patient satisfaction with rivaroxaban therapy contribute to overall favorable clinical outcomes.

Transcatheter closure of patent foramen ovale for secondary prevention of ischemic stroke: Quantitative synthesis of pooled randomized trial data.

PubMed

Hakeem, Abdul; Cilingiroglu, Mehmet; Katramados, Angelos; Boudoulas, Konstantinos Dean; Iliescu, Cezar; Gundogdu, Betul; Marmagkiolis, Konstantinos

2018-01-14

To evaluate the safety and efficacy of percutaneous device closure of patent foramen ovale (PFO) for secondary prevention of ischemic stroke BACKGROUND: Stroke remains the leading cause of serious long-term disability in the United States. The effectiveness of a percutaneous PFO closure in the prevention of recurrent cryptogenic strokes has not been established. We performed a literature search using PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar, and Internet-based sources from January 2003 to September 2017. Randomized controlled trails (RCTs) comparing percutaneous PFO closure to medical therapy alone. Five RCTs (CLOSURE I, PC Trial, REDUCE, RESPECT, and CLOSE) with 1,829 patients in the device group and 1,611 patients in the medical group met inclusion criteria. The cumulative incidence of recurrent stroke was 2.02% in the PFO closure arm and 4.4% in the medical therapy group (RR 0.42, 95%CI 0.20, 0.91; P = 0.03). There was no difference in the incidence of death [0.7% vs. 0.9%; RR 0.76 (95% CI 0.35, 1.64), P = 0.49] or adverse events during the follow-up period [24.6% vs. 23.7% (RR 1.03; 95% CI 0.91, 1.16), P = 0.65] between the closure and medical therapy groups. Incidence of atrial fibrillation was significantly higher in closure group compared to medical therapy [4% vs. 0.6% (RR 4.73; 95% CI 2.09, 10.70), P = 0.0002]. The comparative effectiveness of PFO closure (compared to medical therapy) was significantly more pronounced in those younger than 45 years, males, larger shunts and disc design platforms (P < 0.05). Based on the results of this analysis of randomized trial data, percutaneous PFO closure appears to be a safe and effective therapeutic option for the secondary prevention of ischemic stroke in patients with PFO and cryptogenic stroke. © 2018 Wiley Periodicals, Inc.

Acupuncture therapy for stroke patients.

PubMed

Li, Xin; Wang, Qiang

2013-01-01

Acupuncture is one of the most important parts of Traditional Chinese Medicine, has been used for more than 3000 years as prevention and treatment for various diseases in China as well as in adjacent regions, and is widely accepted in western countries in recent years. More and more clinical trials revealed that acupuncture shows positive effect in stroke, not only as a complementary and alternative medicine for poststroke rehabilitation but also as a preventive strategy which could induce cerebral ischemic tolerance, especially when combined with modern electrotherapy. Acupuncture has some unique characteristics, which include acupoint specificity and parameter-dependent effect. It also involves complicated mechanism to exert the beneficial effect on stroke. Series of clinical trials have shown that acupuncture primarily regulates the release of neurochemicals, hemorheology, cerebral microcirculation, metabolism, neuronal activity, and the function of specific brain region. Animal studies showed that the effects of acupuncture therapy on stroke were possibly via inhibition of postischemic inflammatory reaction, stimulation of neurogenesis and angiogenesis, and influence on neural plasticity. Mechanisms for its preconditioning effect include activity enhancement of antioxidant, regulation of the endocannabinoid system, and inhibition of apoptosis. Although being controversial, acupuncture is a promising preventive and treatment strategy for stroke, but further high-quality clinical trials would be needed to provide more confirmative evidence. © 2013 Elsevier Inc. All rights reserved.

Patent Foramen Ovale Closure for Secondary Prevention of Cryptogenic Stroke: Updated Meta-Analysis of Randomized Clinical Trials.

PubMed

Vaduganathan, Muthiah; Qamar, Arman; Gupta, Ankur; Bajaj, Navkaranbir; Golwala, Harsh B; Pandey, Ambarish; Bhatt, Deepak L

2018-05-01

Patent foramen ovale closure represents a potential secondary prevention strategy for cryptogenic stroke, but available trials have varied by size, device studied, and follow-up. We conducted a systematic search of published randomized clinical trials evaluating patent foramen ovale closure versus medical therapy in patients with recent stroke or transient ischemic attack using PubMED, EMBASE, and Cochrane through September 2017. Weighting was by random effects models. Of 480 studies screened, we included 5 randomized clinical trials in the meta-analysis in which 3440 patients were randomized to patent foramen ovale closure (n = 1829) or medical therapy (n = 1611) and followed for an average of 2.0 to 5.9 years. Index stroke/transient ischemic attack occurred within 6 to 9 months of randomization. The primary end point was composite stroke/transient ischemic attack and death (in 3 trials) or stroke alone (in 2 trials). Patent foramen ovale closure reduced the primary end point (0.70 vs 1.48 events per 100 patient-years; risk ratio [RR], 0.52 [0.29-0.91]; I 2  = 55.0%) and stroke/transient ischemic attack (1.04 vs 2.00 events per 100 patient-years; RR, 0.55 [0.37-0.82]; I 2  = 42.2%) with modest heterogeneity compared with medical therapy. Procedural bleeding was not different between study arms (1.8% vs 1.8%; RR, 0.94 [0.49-1.83]; I 2  = 29.2%), but new-onset atrial fibrillation/flutter was increased with patent foramen ovale closure (6.6% vs 0.7%; RR, 4.69 [2.17-10.12]; I 2  = 29.3%). In patients with recent cryptogenic stroke, patent foramen ovale closure reduces recurrent stroke/transient ischemic attack compared with medical therapy, but is associated with a higher risk of new-onset atrial fibrillation/flutter. Copyright © 2018 Elsevier Inc. All rights reserved.

Blood Pressure Reduction and Secondary Stroke Prevention: A Systematic Review and Metaregression Analysis of Randomized Clinical Trials.

PubMed

Katsanos, Aristeidis H; Filippatou, Angeliki; Manios, Efstathios; Deftereos, Spyridon; Parissis, John; Frogoudaki, Alexandra; Vrettou, Agathi-Rosa; Ikonomidis, Ignatios; Pikilidou, Maria; Kargiotis, Odysseas; Voumvourakis, Konstantinos; Alexandrov, Anne W; Alexandrov, Andrei V; Tsivgoulis, Georgios

2017-01-01

Current recommendations do not specifically address the optimal blood pressure (BP) reduction for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention. For all reported events during each eligible study period, we calculated the corresponding risk ratios to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. On the basis of the reported BP values, we performed univariate metaregression analyses according to the achieved BP values under the random-effects model (Method of Moments) for those adverse events reported in ≥10 total subgroups of included randomized controlled clinical trials. In pairwise meta-analyses, antihypertensive treatment lowered the risk for recurrent stroke (risk ratio, 0.73; 95% confidence interval, 0.62-0.87; P<0.001), disabling or fatal stroke (risk ratio, 0.71; 95% confidence interval, 0.59-0.85; P<0.001), and cardiovascular death (risk ratio, 0.85; 95% confidence interval, 0.75-0.96; P=0.01). In metaregression analyses, systolic BP reduction was linearly related to the lower risk of recurrent stroke (P=0.049), myocardial infarction (P=0.024), death from any cause (P=0.001), and cardiovascular death (P<0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (P=0.026) and all-cause mortality (P=0.009). Funnel plot inspection and Egger statistical test revealed no evidence of publication bias. The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebrovascular and cardiovascular events. Strict and aggressive BP control seems to be essential for effective secondary stroke prevention. © 2016 American Heart Association, Inc.

Efficacy of Intensive Control of Glucose in Stroke Prevention: A Meta-Analysis of Data from 59197 Participants in 9 Randomized Controlled Trials

PubMed Central

Zhang, Chi; Zhou, Yu-Hao; Xu, Chun-Li; Chi, Feng-Ling; Ju, Hai-Ning

2013-01-01

Background The efficacy of treatments that lower glucose in reducing the risk of incident stroke remains unclear. We therefore did a systematic review and meta-analysis to evaluate the efficacy of intensive control of glucose in the prevention of stroke. Methodology/Principal Findings We systematically searched Medline, EmBase, and the Cochrane Library for trials published between 1950 and June, 2012. We included randomized controlled trials that reported on the effects of intensive control of glucose on incident stroke compared with standard care. Summary estimates of relative risk (RR) reductions were calculated with a random effects model, and the analysis was further stratified by factors that could affect the treatment effects. Of 649 identified studies, we included nine relevant trials, which provided data for 59197 patients and 2037 events of stroke. Overall, intensive control of glucose as compared to standard care had no effect on incident stroke (RR, 0.96; 95%CI 0.88–1.06; P = 0.445). In the stratified analyses, a beneficial effect was seen in those trials when body mass index (BMI) more than 30 (RR, 0.86; 95%CI: 0.75–0.99; P = 0.041). No other significant differences were detected between the effect of intensive control of glucose and standard care when based on other subset factors. Conclusions/Significance Our study indicated intensive control of glucose can effectively reduce the risk of incident stroke when patients with BMI more than 30. PMID:23372729

Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial.

PubMed

Kasner, Scott E; Lavados, Pablo; Sharma, Mukul; Wang, Yongjun; Wang, Yilong; Dávalos, Antoni; Shamalov, Nikolay; Cunha, Luis; Lindgren, Arne; Mikulik, Robert; Arauz, Antonio; Lang, Wilfried; Czlonkowska, Anna; Eckstein, Jens; Gagliardi, Rubens; Amarenco, Pierre; Ameriso, Sebastián F; Tatlisumak, Turgut; Veltkamp, Roland; Hankey, Graeme J; Toni, Danilo S; Bereczki, Daniel; Uchiyama, Shinichiro; Ntaios, George; Yoon, Byung-Woo; Brouns, Raf; DeVries Basson, M M; Endres, Matthias; Muir, Keith; Bornstein, Natan; Ozturk, Serefnur; O'Donnell, Martin; Mundl, Hardi; Pater, Calin; Weitz, Jeffrey; Peacock, W Frank; Swaminathan, Balakumar; Kirsch, Bodo; Berkowitz, Scott D; Peters, Gary; Pare, Guillaume; Themeles, Ellison; Shoamanesh, Ashkan; Connolly, Stuart J; Hart, Robert G

2018-06-01

The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Prevention of Stroke with Ticagrelor in Patients with Prior Myocardial Infarction: Insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54).

PubMed

Bonaca, Marc P; Goto, Shinya; Bhatt, Deepak L; Steg, P Gabriel; Storey, Robert F; Cohen, Marc; Goodrich, Erica; Mauri, Laura; Ophuis, Ton Oude; Ruda, Mikhail; Špinar, Jindřich; Seung, Ki-Bae; Hu, Dayi; Dalby, Anthony J; Jensen, Eva; Held, Peter; Morrow, David A; Braunwald, Eugene; Sabatine, Marc S

2016-09-20

In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population. Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis. Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001). High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562. © 2016 American Heart Association, Inc.

Blood pressure as a therapeutic target in stroke.

PubMed

Armario, Pedro; de la Sierra, Alejandro

2009-01-01

Stroke, as a clinical manifestation of the cardiovascular diseases, is one of the leading causes of death and disability in both developed and developing countries. Hypertension is by far, the most important risk factor for stroke. Epidemiological data indicate that the risk of stroke increases with both systolic and diastolic blood pressure elevation, from levels of 115/75 mmHg. It is also evident that most adults worldwide have values above these limits, thus emphasizing the importance of blood pressure as a risk factor for stroke. Clinical trials of antihypertensive treatment, both in studies that have compared active drugs against placebo or in those comparing different types of drugs have clearly demonstrated a protective effect of blood pressure reduction in the prevention of stroke. The degree of protection is directly related to blood pressure reduction and, the lower the level, the better the prognosis. Although data on secondary stroke prevention are scarcer, studies also seem to indicate that lowering blood pressure with antihypertensive treatment protects against stroke recurrence. At the present moment there is still uncertainty on 2 different aspects regarding the relationship between antihypertensive treatment and stroke. First, the blood pressure management during acute stroke has not adequately investigated in clinical trials. Second, the possibility of a protective role of specific types of antihypertensive drugs beyond blood pressure reduction is a matter of debate. Independently of these unresolved issues, prevention of hypertension development by lifestyle changes and adequate treatment and control to the hypertensive population will be a very effective measure in reducing stroke incidence, stroke recurrence, and stroke mortality.

Antihypertensive treatment and stroke prevention: are angiotensin receptor blockers superior to other antihypertensive agents?

PubMed

Armario, Pedro; de la Sierra, Alejandro

2009-06-01

Stroke remains a common vascular event with high mortality and morbidity. After heart disease, stroke is the second leading cause of death worldwide in adult persons. Silent or subclinical stroke is likely to occur with even greater frequency than clinical stroke and increases the risk of subsequent cerebrovascular events. Hypertension is by far the single most important controllable risk factor for stroke. The relationship between blood pressure (BP) and stroke mortality is strong, linear, and continuous in subjects with levels of BP higher than 115/75 mm Hg. Blood pressure reduction by antihypertensive treatment is clearly efficacious in the prevention of stroke (both primary and secondary). Although meta-analyses suggest that BP reduction, per se, is the most important determinant for stroke risk reduction, the question is if specific classes of antihypertensive drugs offer special protection against stroke is still controversial. Some studies have suggested that angiotensin receptors blockers (ARBs) appear to offer additional protection against stroke. This has been hypothesized in studies in hypertensives, such as LIFE and SCOPE, and especially in the only comparative trial focused on secondary stroke prevention. In the MOSES trial, the comparison of eprosartan versus nitrendipine in patients with a previous stroke resulted, despite a similar BP reduction, in a significant reduction in the primary composite endpoint of total mortality plus cardiovascular and cerebrovascular events, including recurrent events. These results may suggest a blood pressure-independent effect of ARBs, which can be mediated through several mechanisms, including their ability to counteract other markers of target organ damage, but also through a direct neuroprotective effect.

Point-of-care cluster randomized trial in stroke secondary prevention using electronic health records.

PubMed

Dregan, Alex; van Staa, Tjeerd P; McDermott, Lisa; McCann, Gerard; Ashworth, Mark; Charlton, Judith; Wolfe, Charles D A; Rudd, Anthony; Yardley, Lucy; Gulliford, Martin C; Trial Steering Committee

2014-07-01

The aim of this study was to evaluate whether the remote introduction of electronic decision support tools into family practices improves risk factor control after first stroke. This study also aimed to develop methods to implement cluster randomized trials in stroke using electronic health records. Family practices were recruited from the UK Clinical Practice Research Datalink and allocated to intervention and control trial arms by minimization. Remotely installed, electronic decision support tools promoted intensified secondary prevention for 12 months with last measure of systolic blood pressure as the primary outcome. Outcome data from electronic health records were analyzed using marginal models. There were 106 Clinical Practice Research Datalink family practices allocated (intervention, 53; control, 53), with 11 391 (control, 5516; intervention, 5875) participants with acute stroke ever diagnosed. Participants at trial practices had similar characteristics as 47,887 patients with stroke at nontrial practices. During the intervention period, blood pressure values were recorded in the electronic health records for 90% and cholesterol values for 84% of participants. After intervention, the latest mean systolic blood pressure was 131.7 (SD, 16.8) mm Hg in the control trial arm and 131.4 (16.7) mm Hg in the intervention trial arm, and adjusted mean difference was -0.56 mm Hg (95% confidence interval, -1.38 to 0.26; P=0.183). The financial cost of the trial was approximately US $22 per participant, or US $2400 per family practice allocated. Large pragmatic intervention studies may be implemented at low cost by using electronic health records. The intervention used in this trial was not found to be effective, and further research is needed to develop more effective intervention strategies. http://www.controlled-trials.com. Current Controlled Trials identifier: ISRCTN35701810. © 2014 American Heart Association, Inc.

Stroke.

PubMed

Hankey, Graeme J

2017-02-11

In the past decade, the definition of stroke has been revised and major advances have been made for its treatment and prevention. For acute ischaemic stroke, the addition of endovascular thrombectomy of proximal large artery occlusion to intravenous alteplase increases functional independence for a further fifth of patients. The benefits of aspirin in preventing early recurrent ischaemic stroke are greater than previously recognised. Other strategies to prevent recurrent stroke now include direct oral anticoagulants as an alternative to warfarin for atrial fibrillation, and carotid stenting as an alternative to endarterectomy for symptomatic carotid stenosis. For acute intracerebral haemorrhage, trials are ongoing to assess the effectiveness of acute blood pressure lowering, haemostatic therapy, minimally invasive surgery, anti-inflammation therapy, and neuroprotection methods. Pharmacological and stem-cell therapies promise to facilitate brain regeneration, rehabilitation, and functional recovery. Despite declining stroke mortality rates, the global burden of stroke is increasing. A more comprehensive approach to primary prevention of stroke is required that targets people at all levels of risk and is integrated with prevention strategies for other diseases that share common risk factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fibrates for secondary prevention of cardiovascular disease and stroke.

PubMed

Wang, Deren; Liu, Bian; Tao, Wendan; Hao, Zilong; Liu, Ming

2015-10-25

Fibrates are a class of drugs characterised by mainly lowering high triglyceride, raising high-density lipoprotein (HDL) cholesterol, and lowering the small dense fraction of low-density lipoprotein (LDL) cholesterol. Their efficacy for secondary prevention of serious vascular events is unclear, and to date no systematic review focusing on secondary prevention has been undertaken. To assess the efficacy and safety of fibrates for the prevention of serious vascular events in people with previous cardiovascular disease (CVD), including coronary heart disease and stroke. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9, 2014) on the Cochrane Library, MEDLINE (OVID, 1946 to October week 1 2014), EMBASE (OVID, 1980 to 2014 week 41), the China Biological Medicine Database (CBM) (1978 to 2014), the Chinese National Knowledge Infrastructure (CNKI) (1979 to 2014), Chinese Science and Technique Journals Database (VIP) (1989 to 2014). We also searched other resources, such as ongoing trials registers and databases of conference abstracts, to identify further published, unpublished, and ongoing studies. We included randomised controlled trials (RCTs) in which a fibrate (for example gemfibrozil, fenofibrate) was compared with placebo or no treatment. We excluded RCTs with only laboratory outcomes. We also excluded trials comparing two different fibrates without a placebo or no-treatment control. Two review authors independently selected trials for inclusion, assessed risk of bias, and extracted the data. We contacted authors of trials for missing data. We included 13 trials involving a total of 16,112 participants. Eleven trials recruited participants with history of coronary heart disease, two trials recruited participants with history of stroke, and one trial recruited participants with a mix of people with CVD. We judged overall risk of bias to be moderate. The meta-analysis (including all fibrate trials) showed evidence for a protective effect of fibrates primarily compared to placebo for the primary composite outcome of non-fatal stroke, non-fatal myocardial infarction (MI), and vascular death (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.94; participants = 16,064; studies = 12; I(2) = 45%, fixed effect). Fibrates were moderately effective for preventing MI occurrence (RR 0.86, 95% CI 0.80 to 0.93; participants = 13,942; studies = 10; I(2) = 24%, fixed effect). Fibrates were not effective against all-cause mortality (RR 0.98, 95% CI 0.91 to 1.06; participants = 13,653; studies = 10; I(2) = 23%), death from vascular causes (RR 0.95, 95% CI 0.86 to 1.05; participants = 13,653; studies = 10; I(2) = 11%, fixed effect), and stroke events (RR 1.03, 95% CI 0.91 to 1.16; participants = 11,719; studies = 6; I(2) = 11%, fixed effect). Excluding clofibrate trials, as the use of clofibrate was discontinued in 2012 due to safety concerns, the remaining class of fibrates were no longer effective in preventing the primary composite outcome (RR 0.90, 95% CI 0.79 to 1.03; participants = 10,320; studies = 7; I(2) = 50%, random effects). However, without clofibrate data, fibrates remained effective in preventing MI (RR 0.85, 95% CI 0.76 to 0.94; participants = 8304; studies = 6; I(2) = 47%, fixed effect). There was no increase in adverse events with fibrates compared to control. Subgroup analyses showed the benefit of fibrates on the primary composite outcome to be consistent irrespective of age, gender, and diabetes mellitus. Moderate evidence showed that the fibrate class can be effective in the secondary prevention of composite outcome of non-fatal stroke, non-fatal MI, and vascular death. However, this beneficial effect relies on the inclusion of clofibrate data, a drug that was discontinued in 2002 due to its unacceptably large adverse effects. Further trials of the use of fibrates in populations with previous stroke and also against a background treatment with statins (standard of care) are required.

Is blood pressure reduction a valid surrogate endpoint for stroke prevention? an analysis incorporating a systematic review of randomised controlled trials, a by-trial weighted errors-in-variables regression, the surrogate threshold effect (STE) and the biomarker-surrogacy (BioSurrogate) evaluation schema (BSES)

PubMed Central

2012-01-01

Background Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i) formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii) determine what blood pressure reduction would predict a stroke benefit. Methods We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE), below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP), a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3). Results In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and diastolic blood pressure was an A grade surrogate endpoint for stroke prevention. In comparison, using the same stroke data sets, no STEs could be estimated for cardiovascular (CV) mortality or all-cause mortality reduction, although the STE for CV mortality approached 25 mmHg for systolic blood pressure. Conclusions In this report we provide the first surrogate threshold effect (STE) values for systolic and diastolic blood pressure. We suggest the STEs have face and content validity, evidenced by the inclusivity of trial populations, subject populations and pharmacologic intervention populations in their calculation. We propose that the STE and STEP metrics offer another method of evaluating the evidence supporting surrogate endpoints. We demonstrate how surrogacy evaluations are strengthened if formally evaluated within specific-context evaluation frameworks using the Biomarker- Surrogate Evaluation Schema (BSES3), and we discuss the implications of our evaluation of blood pressure on other biomarkers and patient-reported instruments in relation to surrogacy metrics and trial design. PMID:22409774

Relationship between risk factor control and vascular events in the SAMMPRIS trial.

PubMed

Turan, Tanya N; Nizam, Azhar; Lynn, Michael J; Egan, Brent M; Le, Ngoc-Anh; Lopes-Virella, Maria F; Hermayer, Kathie L; Harrell, Jamie; Derdeyn, Colin P; Fiorella, David; Janis, L Scott; Lane, Bethany; Montgomery, Jean; Chimowitz, Marc I

2017-01-24

The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study is the first stroke prevention trial to include protocol-driven intensive management of multiple risk factors. In this prespecified analysis, we aimed to investigate the relationship between risk factor control during follow-up and outcome of patients in the medical arm of SAMMPRIS. Data from SAMMPRIS participants in the medical arm (n = 227) were analyzed. Risk factors were recorded at baseline, 30 days, 4 months, and then every 4 months for a mean follow-up of 32 months. For each patient, values for all risk factor measures were averaged and dichotomized as in or out of target. Participants who were out of target for systolic blood pressure and physical activity, as well as those with higher mean low-density lipoprotein cholesterol and non-high-density lipoprotein, were more likely to have a recurrent vascular event (stroke, myocardial infarction, or vascular death) at 3 years compared to those who had good risk factor control. In the multivariable analysis, greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death (odds ratio 0.6, confidence interval 0.4-0.8). Raised blood pressure, cholesterol, and physical inactivity should be aggressively treated in patients with intracranial atherosclerosis to prevent future vascular events. Physical activity, which has not received attention in stroke prevention trials, was the strongest predictor of a good outcome in the medical arm in SAMMPRIS. NCT00576693. © 2016 American Academy of Neurology.

Effect of peer education on stroke prevention: the prevent recurrence of all inner-city strokes through education randomized controlled trial.

PubMed

Kronish, Ian M; Goldfinger, Judith Z; Negron, Rennie; Fei, Kezhen; Tuhrim, Stanley; Arniella, Guedy; Horowitz, Carol R

2014-11-01

Efforts to reduce disparities in recurrent stroke among Black and Latino stroke survivors have met with limited success. We aimed to determine the effect of peer education on secondary stroke prevention among predominantly minority stroke survivors. Between 2009 and 2012, we enrolled 600 stroke or transient ischemic attack survivors from diverse, low-income communities in New York City into a 2-arm randomized clinical trial that compared a 6 week (1 session/week), peer-led, community-based, stroke prevention self-management group workshop (N=301) to a wait-list control group (N=299). The primary outcome was the proportion with a composite of controlled blood pressure (<140/90 mm Hg), low-density lipoprotein cholesterol <100 mg/dL, and use of antithrombotic medications at 6 months. Secondary outcomes included control of the individual stroke risk factors. All analyses were by intent-to-treat. There was no difference in the proportion of intervention and control group participants achieving the composite outcome (34% versus 34%; P=0.98). The proportion with controlled blood pressure at 6 months was greater in the intervention group than in the control group (76% versus 67%; P=0.02). This corresponded to a greater change in systolic blood pressure in the intervention versus control group (-3.63 SD, 19.81 mm Hg versus +0.34 SD, 23.76 mm Hg; P=0.04). There were no group differences in the control of cholesterol or use of antithrombotics. A low-cost peer education self-management workshop modestly improved blood pressure, but not low-density lipoprotein cholesterol or antithrombotic use, among stroke and transient ischemic attack survivors from vulnerable, predominantly minority urban communities. http://www.clinicaltrials.gov/show/NCT0102727. Unique identifier: NCT01027273. © 2014 American Heart Association, Inc.

Asian strategy for stroke prevention in atrial fibrillation.

PubMed

Chiang, Chern-En; Wang, Kang-Ling; Lin, Shing-Jong

2015-10-01

Atrial fibrillation (AF) has become a major health burden in Asia. It is estimated that in year 2050 Asia will have 72 million AF patients, and 2.9 million among them will suffer from AF-associated stroke. Asian AF patients have similar cardiovascular co-morbidities as westerns, and the recently developed CHA2DS2-VASc score remains valid in predicting stroke risk in Asians, outperforming other scoring systems. There is little evidence supporting a role of aspirin in preventing AF-associated stroke in Asians. Warfarin is effective for the prevention of stroke in Asians, but is very difficult to use. Warfarin-induced bleeding events are more common in Asians. Four major clinical trials have been performed to test non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin in the stroke prevention in AF. Warfarin produced higher risk of major bleeding and intra-cranial haemorrhage in Asians compared with those in non-Asians, even though anticoagulation intensity was lower in Asians. All these trials consistently demonstrated that NOACs were superior or non-inferior to warfarin. The benefits of NOACs were especially robust in Asians. The relative risk reduction in most of the efficacy endpoints and the safety endpoints was numerically greater in Asians than in non-Asians. There was no evidence of increased risk of gastro-intestinal bleeding associated with NOACs in Asians. Unless in a few conditions when NOACs are contraindicated, NOACs are preferred medications in the stroke prevention for AF in Asians. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Secondary prevention lifestyle interventions initiated within 90 days after TIA or 'minor' stroke: a systematic review and meta-analysis of rehabilitation programmes.

PubMed

Heron, Neil; Kee, Frank; Cardwell, Christopher; Tully, Mark A; Donnelly, Michael; Cupples, Margaret E

2017-01-01

Strokes are often preceded by a transient ischaemic attack (TIA) or 'minor' stroke. The immediate period after a TIA/minor stroke is a crucial time to initiate secondary prevention. However, the optimal approach to prevention, including non-pharmacological measures, after TIA is not clear. To systematically review evidence about the effectiveness of delivering secondary prevention, with lifestyle interventions, in comprehensive rehabilitation programmes, initiated within 90 days of a TIA/minor stroke. Also, to categorise the specific behaviour change techniques used. The review identified randomised controlled trials by searching the Cochrane Library, Ovid MEDLINE, Ovid EMBASE, Web of Science, EBSCO CINAHL and Ovid PsycINFO. Two review authors independently screened titles and abstracts for eligibility (programmes initiated within 90 days of event; outcomes reported for TIA/minor stroke) and extracted relevant data from appraised studies; a meta-analysis was used to synthesise the results. A total of 31 potentially eligible papers were identified and four studies, comprising 774 patients post-TIA or minor stroke, met the inclusion criteria; two had poor methodological quality. Individual studies reported increased aerobic capacity but meta-analysis found no significant change in resting and peak systolic blood pressure, resting heart rate, aerobic capacity, falls, or mortality. The main behaviour change techniques were goal setting and instructions about how to perform given behaviours. There is limited evidence of the effectiveness of early post-TIA rehabilitation programmes with preventive lifestyle interventions. Further robust randomised controlled trials of comprehensive rehabilitation programmes that promote secondary prevention and lifestyle modification immediately after a TIA are needed. © British Journal of General Practice 2017.

Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

PubMed

Spencer, Ryan J; Amerena, John V

2015-12-01

Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20 mg daily for patients with normal renal function and 15 mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30 ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF.

Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks: Results of an Analysis of 13 Biomarkers From the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trial.

PubMed

Ganz, Peter; Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Bao, Weihang; Preston, Gregory M; Welch, K Michael A

2017-12-01

Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes. We conducted a case-cohort study of 2176 participants; 562 had outcome strokes and 1614 were selected randomly from those without outcome strokes. Time to stroke was evaluated by Cox proportional hazards models. There was no association between time to stroke and lipoprotein-associated phospholipase A 2 , monocyte chemoattractant protein-1, resistin, matrix metalloproteinase-9, N-terminal fragment of pro-B-type natriuretic peptide, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, or soluble CD40 ligand. In adjusted analyses, osteopontin (hazard ratio per SD change, 1.362; P <0.0001), neopterin (hazard ratio, 1.137; P =0.0107), myeloperoxidase (hazard ratio, 1.177; P =0.0022), and adiponectin (hazard ratio, 1.207; P =0.0013) were independently associated with outcome strokes. After adjustment for the Stroke Prognostic Instrument-II and treatment, osteopontin, neopterin, and myeloperoxidase remained independently associated with outcome strokes. The addition of these 3 biomarkers to Stroke Prognostic Instrument-II increased the area under the receiver operating characteristic curve by 0.023 ( P =0.015) and yielded a continuous net reclassification improvement (29.1%; P <0.0001) and an integrated discrimination improvement (42.3%; P <0.0001). Osteopontin, neopterin, and myeloperoxidase were independently associated with the risk of recurrent stroke and improved risk classification when added to a clinical risk algorithm. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00147602. © 2017 American Heart Association, Inc.

Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials.

PubMed

Hughey, Andrew B; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Besley, Dennis; Krol, Gregory D; Ahsan, Syed; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2018-06-14

Randomized controlled trials (RCTs) examining warfarin use for stroke prevention in atrial fibrillation (AF) may not accurately reflect real-world populations. We aimed to determine the representativeness of the RCT populations to real-world patients and to describe differences in the characteristics of trial populations from trial eligible patients in a real-world setting. We hypothesized that a significant fraction of real-world patients would not qualify for the RE-LY, ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the studies may have more strokes and bleeding events. We compared the inclusion and exclusion criteria, patient characteristics, and clinical outcomes from RE-LY, ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2 ), a regional network of six community- and academic-based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI 2 registry taking warfarin, approximately 40-60% would meet the selection criteria used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%). The most common reasons for exclusion from one or more trial were anemia (15.1%), other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial-eligible MAQI 2 patients were older, more frequently female, with a higher rate of paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and previous myocardial infarction than the trial populations. MAQI 2 patients eligible for each trial had a lower rate of stroke and similar rate of major bleeding than was observed in the trials. A sizable proportion of real-world AF patients managed in anticoagulation clinics would not have been eligible for the RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and bleeding risk among real-world AF patients on warfarin may not be congruent with published clinical trial data.

Telmisartan on top of antihypertensive treatment does not prevent progression of cerebral white matter lesions in the prevention regimen for effectively avoiding second strokes (PRoFESS) MRI substudy.

PubMed

Weber, Ralph; Weimar, Christian; Blatchford, Jon; Hermansson, Karin; Wanke, Isabel; Möller-Hartmann, Claudia; Gizewski, Elke R; Forsting, Michael; Demchuk, Andrew M; Sacco, Ralph L; Saver, Jeffrey L; Warach, Steven; Diener, Hans-Christoph; Diehl, Anke

2012-09-01

High blood pressure is one of the main risk factors for cerebral white matter lesions (WMLs). There is limited evidence from one randomized trial that blood pressure-lowering is able to slow WML progression. We investigated whether telmisartan prevents WML progression in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. This predefined substudy comprised 771 patients (mean age, 65 years) with recent ischemic stroke of noncardioembolic origin who received telmisartan or placebo during a mean follow-up of 27.9 (SD, 7.6) months and had 2 evaluable MRI examinations after index stroke and at study closeout. All MRI scans were centrally adjudicated for progression of periventricular and subcortical WML by 2 neuroradiologists blinded to treatment allocation. Mean blood pressure was 3.0/1.3 mm Hg lower with telmisartan compared with placebo at follow-up MRI. There was no statistically significant difference in progression of the mean periventricular WML score (least squares mean difference, 0.14; 95% CI, -0.12 to 0.39; P=0.29) and mean subcortical WML diameter (least squares mean difference, -0.35 mm; 95% CI, -1.00 to 0.31 mm; P=0.30) during follow-up between patients on telmisartan and placebo. Treatment with telmisartan on top of existing antihypertensive medication did not result in significant blood pressure-lowering and did not prevent the progression of WML in patients with a recent ischemic stroke in this patient cohort. Our analysis is limited by the relatively short follow-up period. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00153062.

Study design of the CLOSURE I Trial: a prospective, multicenter, randomized, controlled trial to evaluate the safety and efficacy of the STARFlex septal closure system versus best medical therapy in patients with stroke or transient ischemic attack due to presumed paradoxical embolism through a patent foramen ovale.

PubMed

Furlan, Anthony J; Reisman, Mark; Massaro, Joseph; Mauri, Laura; Adams, Harold; Albers, Gregory W; Felberg, Robert; Herrmann, Howard; Kar, Saibal; Landzberg, Michael; Raizner, Albert; Wechsler, Lawrence

2010-12-01

Some strokes of unknown etiology may be the result of a paradoxical embolism traversing through a nonfused foramen ovale (patent foramen ovale [PFO]). The utility of percutaneously placed devices for treatment of patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO is unknown. In addition, there are no clear data about the utility of medical interventions or other surgical procedures in this situation. Despite limited data, many patients are being treated with PFO closure devices. Thus, there is a strong need for clinical trials that test the potential efficacy of PFO occlusive devices in this situation. To address this gap in medical knowledge, we designed the CLOSURE I trial, a randomized, clinical trial comparing the use of a percutaneously placed PFO occlusive device and best medical therapy versus best medical therapy alone for prevention of recurrent ischemic neurologic symptoms among persons with TIA or ischemic stroke. This prospective, multicenter, randomized, controlled trial has finished enrollment. Two-year follow-up for all 910 patients is required. The primary end point is the 2-year incidence of stroke or TIA, all-cause mortality for the first 30 days, and neurologic mortality from ≥ 31 days of follow-up, as adjudicated by a panel of physicians who are unaware of treatment allocation. This article describes the rationale and study design of CLOSURE I. This trial should provide information as to whether the STARFlex septal closure system is safe and more effective than best medical therapy alone in preventing recurrent stroke/TIA and mortality in patients with PFO and whether the STARFlex septal closure device can demonstrate superiority compared with best medical therapy alone. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00201461.

Impact and risk factors of post-stroke bone fracture

PubMed Central

Huo, Kang; Hashim, Syed I; Yong, Kimberley L Y; Su, Hua; Qu, Qiu-Min

2016-01-01

Bone fracture occurs in stroke patients at different times during the recovery phase, prolonging recovery time and increasing medical costs. In this review, we discuss the potential risk factors for post-stroke bone fracture and preventive methods. Most post-stroke bone fractures occur in the lower extremities, indicating fragile bones are a risk factor. Motor changes, including posture, mobility, and balance post-stroke contribute to bone loss and thus increase risk of bone fracture. Bone mineral density is a useful indicator for bone resorption, useful to identify patients at risk of post-stroke bone fracture. Calcium supplementation was previously regarded as a useful treatment during physical rehabilitation. However, recent data suggests calcium supplementation has a negative impact on atherosclerotic conditions. Vitamin D intake may prevent osteoporosis and fractures in patients with stroke. Although drugs such as teriparatide show some benefits in preventing osteoporosis, additional clinical trials are needed to determine the most effective conditions for post-stroke applications. PMID:26929915

Electrical stimulation for preventing and treating post-stroke shoulder pain.

PubMed

Price, C I; Pandyan, A D

2000-01-01

Shoulder pain after stroke is common and disabling. The optimal management is uncertain, but electrical stimulation (ES) is often used to treat and prevent pain. The objective of this review was to determine the efficacy of any form of surface ES in the prevention and / or treatment of pain around the shoulder at any time after stroke. We searched the Cochrane Stroke Review Group trials register and undertook further searches of MEDLINE, EMBASE and CINAHL. Contact was established with equipment manufacturers and centres that have published on the topic of ES. We considered all randomised trials that assessed any surface ES technique (functional electrical stimulation (FES), transcutaneous electrical nerve stimulation (TENS) or other), applied at any time since stroke for the purpose of prevention or treatment of shoulder pain. Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. Four trials (a total of 170 subjects) fitted the inclusion criteria. Study design and ES technique varied considerably, often precluding the combination of studies. Population numbers were small. There was no significant change in pain incidence (Odds Ratio (OR) 0.64; 95% CI 0.19 to 2.14) or change in pain intensity (Standardised Mean Difference (SMD) 0.13; 95% CI -1.0 to 1.25) after ES treatment compared to control. There was a significant treatment effect in favour of ES for improvement in pain-free range of passive humeral lateral rotation (Weighted Mean Difference (WMD) 9.17; 95% CI 1.43 to 16.91). In these studies ES reduced the severity of glenohumeral subluxation (SMD -1.13; 95% CI -1.66 to -0.60), but there was no significant effect on upper limb motor recovery (SMD 0.24; 95% CI -0.14 to 0.62) or upper limb spasticity (WMD 0.05; 95% CI -0.28 to 0.37). There did not appear to be any negative effects of electrical stimulation at the shoulder. The evidence from randomised controlled trials so far does not confirm or refute that ES around the shoulder after stroke influences reports of pain, but there do appear to be benefits for passive humeral lateral rotation. A possible mechanism is through the reduction of glenohumeral subluxation. Further studies are required.

Electrical stimulation for preventing and treating post-stroke shoulder pain: a systematic Cochrane review.

PubMed

Price, C I; Pandyan, A D

2001-02-01

Shoulder pain after stroke is common and disabling. The optimal management is uncertain, but electrical stimulation (ES) is often used to treat and prevent pain. The objective of this review was to determine the efficacy of any form of surface ES in the prevention and/or treatment of pain around the shoulder at any time after stroke. We searched the Cochrane Stroke Review Group trials register and undertook further searches of Medline, Embase and CINAHL. Contact was established with equipment manufacturers and centres that have published on the topic of ES. We considered all randomized trials that assessed any surface ES technique (functional electrical stimulation (FES), transcutaneous electrical nerve stimulation (TENS) or other), applied at any time since stroke for the purpose of prevention or treatment of shoulder pain. Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. Four trials (a total of 170 subjects) fitted the inclusion criteria. Study design and ES technique varied considerably, often precluding the combination of studies. Population numbers were small. There was no significant change in pain incidence (odds ratio (OR) 0.64; 95% CI 0.19-2.14) or change in pain intensity (standardized mean difference (SMD) 0.13; 95% CI -1.0-1.25) after ES treatment compared with control. There was a significant treatment effect in favour of ES for improvement in pain-free range of passive humeral lateral rotation (weighted mean difference (WMD) 9.17; 95% CI 1.43-16.91). In these studies ES reduced the severity of glenohumeral subluxation (SMD -1.13; 95% CI -1.66 to -0.60), but there was no significant effect on upper limb motor recovery (SMD 0.24; 95% CI -0.14-0.62) or upper limb spasticity (WMD 0.05; 95% CI -0.28-0.37). There did not appear to be any negative effects of electrical stimulation at the shoulder. The evidence from randomized controlled trials so far does not confirm or refute that ES around the shoulder after stroke influences reports of pain, but there do appear to be benefits for passive humeral lateral rotation. A possible mechanism is through the reduction of glenohumeral subluxation. Further studies are required.

Review of economics and cost-effectiveness analyses of anticoagulant therapy for stroke prevention in atrial fibrillation in the US.

PubMed

von Schéele, Birgitta; Fernandez, Maria; Hogue, Susan Lynn; Kwong, Winghan Jacqueline

2013-05-01

To summarize the available evidence on the issues in health economics related to oral anticoagulation for stroke prevention in atrial fibrillation (AF) in the US. A literature review was performed using PubMed, EMBASE, Cochrane Library, and International Pharmaceutical Abstracts, as well as the websites of professional organizations. The search was conducted according to a prespecified protocol, limiting articles to those published in English from 2001 to October 2012 and focused on the economics associated with AF and AF-related stroke in the US. Data from 27 studies were extracted and included in the review. Strokes in patients with AF are more debilitating and have higher recurrence rates and mortality compared with strokes unrelated to AF. However, data describing the long-term cost of AF-related stroke and stroke subtypes remain limited. The costs of major gastrointestinal (GI) bleeding and intracranial bleeding related to warfarin are significant, whereas the costs of the more frequent minor GI bleeding are relatively low. Overall, the cost-effectiveness of warfarin versus aspirin or no treatment in patients with at least 1 risk factor for stroke is well established. Economic evaluations based on results from randomized controlled clinical trials generally found that new anticoagulants were a cost-effective alternative to warfarin for stroke prevention in AF. However, these cost-effectiveness results are highly sensitive to how well optimal international normalized ratio control is maintained (within target of 2.0-3.0) for warfarin and the time horizon used for analysis. Time in therapeutic range for warfarin in routine clinical practice was lower than in clinical trials, as shown by previous studies. This review identified several areas of uncertainty regarding the economic benefit of anticoagulants. The generalizability of cost-effectiveness results of anticoagulant therapy in AF based on clinical trial data must be confirmed by comparative effectiveness research conducted in the real-world setting.

Should preventive antibiotics be used in patients with acute stroke? A systematic review and meta-analysis of randomized controlled trials.

PubMed

Zheng, Feng; Spreckelsen, Niklas von; Zhang, Xintong; Stavrinou, Pantelis; Timmer, Marco; Dohmen, Christian; Goldbrunner, Roland; Cao, Fang; Zhang, Qiang; Ran, Qishan; Li, Gang; Fan, Ruiming; Yao, Shengtao; Krischek, Boris

2017-01-01

Infection is a common complication in acute stroke. Whether or not preventive antibiotics reduce the risk of infection or even lead to a favorable outcome and reduction of mortality after a stroke still remains equivocal. This review was performed to update the current knowledge on the effect and possible benefits of prophylactic antibiotic therapy in patients with stroke. A systematic review and meta-analysis of preventive antibiotics`effect on the incidence of infection, favorable outcome (mRS≤2) and mortality in patients with acute stroke is performed with relevant randomized controlled trials. Six studies were identified, involving 4125 participants. Compared with the control group, the treated groups were significantly less prone to suffer from early overall infections [RR = 0.52, 95%CI (0.39, 0.70), p<0.0001], early pneumonia [RR = 0.64, 95%CI (0.42, 0.96), p = 0.03] and early urinary tract infections [RR = 0.35, 95%CI (0.25, 0.48), p<0.00001]. However, there was no significant difference in overall mortality [RR = 1.07, 95%CI (0.90, 1.27), p = 0.44], early mortality [RR = 0.99, 95%CI (0.78, 1.26), p = 0.92], late mortality [RR = 1.12, 95%CI (0.94, 1.35), p = 0.21] or favorable outcome [RR = 1.00, 95%CI (0.92, 1.08), p = 0.98]. Although preventive antibiotic treatment did reduce the occurrence of early overall infections, early pneumonia and early urinary tract infection in patients with acute stroke, this advantage was not eventually translated to a favorable outcome and reduction in mortality. Future studies are warranted to identify any subgroup of stroke patients who might benefit from preventive antibiotic treatment.

Patent foramen ovale closure with GORE HELEX or CARDIOFORM Septal Occluder vs. antiplatelet therapy for reduction of recurrent stroke or new brain infarct in patients with prior cryptogenic stroke: Design of the randomized Gore REDUCE Clinical Study.

PubMed

Kasner, Scott E; Thomassen, Lars; Søndergaard, Lars; Rhodes, John F; Larsen, Coby C; Jacobson, Joth

2017-12-01

Rationale The utility of patent foramen ovale (PFO) closure for secondary prevention in patients with prior cryptogenic stroke is uncertain despite multiple randomized trials completed to date. Aims The Gore REDUCE Clinical Study (REDUCE) aims to establish superiority of patent foramen ovale closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke. Methods and design This controlled, open-label trial randomized 664 subjects with cryptogenic stroke at 63 multinational sites in a 2:1 ratio to either antiplatelet therapy plus patent foramen ovale closure (with GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder) or antiplatelet therapy alone. Subjects will be prospectively followed for up to five years. Neuroimaging is required for all subjects at baseline and at two years or study exit. Study outcomes The two co-primary endpoints for the study are freedom from recurrent clinical ischemic stroke through at least 24 months post-randomization and incidence of new brain infarct (defined as clinical ischemic stroke or silent brain infarct) through 24 months. The primary analyses are an unadjusted log-rank test and a binomial test of subject-based proportions, respectively, both on the intent-to-treat population, with adjustment for testing multiplicity. Discussion The REDUCE trial aims to target a patient population with truly cryptogenic strokes. Medical therapy is limited to antiplatelet agents in both arms thereby reducing confounding. The trial should determine whether patent foramen ovale closure with the Gore septal occluders is safe and more effective than medical therapy alone for the prevention of recurrent clinical ischemic stroke or new silent brain infarct; the neuroimaging data will provide an opportunity to further support the proof of concept. The main results are anticipated in 2017. Registration Clinical trial registration-URL: http://clinicaltrials.gov/show/NCT00738894.

Novel anticoagulants for stroke prevention in patients with atrial fibrillation.

PubMed

Jalota, A; Scarabelli, T M; Saravolatz, L; Bakhsh, M U; Agrawal, P; Jalota, R; Chen-Scarabelli, C; Fuster, V; Halperin, J

2014-06-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia that can potentially result in stroke. Vitamin K antagonists (VKA) like warfarin were for many decades the only oral anticoagulants available for stroke prevention in patients with non-valvular atrial fibrillation (AF) at high risk of stroke. Recently, new oral anticoagulants (NOACS) have been introduced that act via direct inhibition of thrombin (dabigatran) or activated factor X (edoxaban, rivaroxaban and apixaban). Unlike VKAs, these anticoagulants do not require routine INR monitoring and posses favorable pharmacological properties. NOACs act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Phase III trials comparing these agents to warfarin for stroke prevention in patients with non-valvular AF demonstrated that they are at least as efficacious and safe as warfarin. Evolution of clinical guidelines to incorporate the new anticoagulants for stroke prevention in non-valvular AF may result in a reduction in the incidence of AF-related strokes. Safe and effective use of these new drugs in clinical practice requires understanding of their distinct pharmacological properties.

Effects of statins on stroke prevention in patients with and without coronary heart disease: a meta-analysis of randomized controlled trials.

PubMed

Briel, Matthias; Studer, Marco; Glass, Tracy R; Bucher, Heiner C

2004-10-15

To assess if lipid-lowering interventions (statins, fibrates, resins, n-3 fatty acids, diet) prevent nonfatal and fatal strokes in patients with and without coronary heart disease. We systematically searched the literature up to August 2002 to retrieve all randomized controlled trials of lipid-lowering interventions that reported nonfatal and fatal stroke and mortality data. The search yielded 65 trials with 200,607 patients for a meta-analysis to determine whether treatment effects differed between types of lipid-lowering interventions and between patient samples with and without coronary heart disease. The risk ratio for nonfatal and fatal stroke for statins as compared with control interventions was 0.82 (95% confidence interval [CI]: 0.76 to 0.90). The corresponding risk ratios for statins as compared with control were 0.75 (95% CI: 0.65 to 0.87) for patients with coronary heart disease and 0.77 (95% CI: 0.62 to 0.95) for those without coronary heart disease. The confidence intervals of risk ratios for nonfatal and fatal stroke associated with fibrates, resins, n-3 fatty acids, and diet all included 1, as did the confidence intervals for these interventions in patients with and without coronary heart disease. Weighted meta-regression analysis suggested a stronger association of stroke reduction with statin treatment than with the extent of cholesterol reduction. This meta-analysis suggests that statins reduce the incidence of stroke in patients with and without coronary heart disease.

Dipyridamole for preventing recurrent ischemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials.

PubMed

Leonardi-Bee, Jo; Bath, Philip M W; Bousser, Marie-Germaine; Davalos, Antoni; Diener, Hans-Christoph; Guiraud-Chaumeil, Bernard; Sivenius, Juhani; Yatsu, Frank; Dewey, Michael E

2005-01-01

Results from randomized controlled trials of dipyridamole, given with or without aspirin, for secondary prevention after ischemic stroke or transient ischemic attack (TIA) have given conflicting results. We performed a meta-analysis using individual patient data from relevant randomized controlled trials. Randomized controlled trials involving dipyridamole in patients with previous ischemic stroke or TIA were sought from searches of the Cochrane Library, other electronic databases, references lists, earlier reviews, and contact with the manufacturer of dipyridamole. Individual patient data were merged from 5 of 7 relevant trials involving 11 459 patients. Results were adjusted for age, gender, qualifying event, and history of previous hypertension. Recurrent stroke was reduced by dipyridamole as compared with control (OR, 0.82; 95% CI, 0.68 to 1.00), and by combined aspirin and dipyridamole versus aspirin alone (OR, 0.78; 95% CI, 0.65 to 0.93), dipyridamole alone (OR, 0.74; 95% CI, 0.60 to 0.90), or control (OR, 0.61; 95% CI, 0.51 to 0.71). The point estimates obtained for the comparisons of aspirin and dipyridamole versus control (OR, 0.63; significant) or versus aspirin (OR, 0.88; nonsignificant) were similar if the data from the largest trial, ESPS II (which provided 57% of data), were excluded. Similar findings were observed for nonfatal stroke. The combination of aspirin and dipyridamole also significantly reduced the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone (OR, 0.84; 95% CI, 0.72 to 0.97), dipyridamole alone (OR, 0.76; 95% CI, 0.64 to 0.90), or control (OR, 0.66; 95% CI, 0.57 to 0.75). Vascular death was not altered in any group. Dipyridamole, given alone or with aspirin, reduces stroke recurrence in patients with previous ischemic cerebrovascular disease. The combination of aspirin and dipyridamole also reduces the composite of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone.

Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation: pooled analysis of SPORTIF III and V clinical trials.

PubMed

Akins, Paul T; Feldman, Harvey A; Zoble, Robert G; Newman, David; Spitzer, Stefan G; Diener, Hans-Christoph; Albers, Gregory W

2007-03-01

Patients with nonvalvular atrial fibrillation and prior stroke or transient ischemic attack (TIA) are at high risk for recurrent stroke. We investigated whether ximelagatran was noninferior to warfarin in patients with prior stroke or TIA. We analyzed pooled data from the SPORTIF III and V trials in patients with prior stroke/TIA. The primary outcome was the composite annual rate of both ischemic and hemorrhagic strokes and systemic embolic events. Secondary analyses considered ischemic and hemorrhagic strokes separately, bleeding, and nonrandomized, concomitant therapy with aspirin < or =100 mg/d. Patients from SPORTIF III (n=3407) and SPORTIF V (n=3922) trials were categorized by prior stroke/TIA (21%) versus no prior stroke/TIA (79%) and by treatment group (ximelagatran vs warfarin). The primary event rate in patients with prior stroke/TIA was 2.83%/y with ximelagatran and 3.27%/y with warfarin (absolute difference, -0.44%; 95% CI, -1.88 to1.01; P=0.625). In those without prior stroke/TIA, the primary event rate was 1.31%/y with ximelagatran and 1.26%/y with warfarin (P=NS). Ischemic strokes outnumbered cerebral hemorrhages with both warfarin (31 of 36) and ximelagatran (30 of 32) treatment (difference between treatments was not significant). Combining aspirin with either anticoagulant was associated with higher rates of major bleeding (1.5%/y with warfarin and 4.95%/y with warfarin plus aspirin, P=0.004; 2.35%/y with ximelagatran and 5.09%/y with ximelagatran plus aspirin, P=0.046) but not lower rates of primary events. Ximelagatran was at least as effective as well-controlled warfarin for the secondary prevention of stroke. The nonrandomized, concomitant treatment with aspirin and anticoagulation was associated with increased bleeding without evidence of a reduction in primary outcome events.

Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men.

PubMed

Zhou, Ziyi; Li, Jianping; Yu, Yaren; Li, Youbao; Zhang, Yan; Liu, Lishun; Song, Yun; Zhao, Min; Wang, Yu; Tang, Genfu; He, Mingli; Xu, Xiping; Cai, Yefeng; Dong, Qiang; Yin, Delu; Huang, Xiao; Cheng, Xiaoshu; Wang, Binyan; Hou, Fan Fan; Wang, Xiaobin; Qin, Xianhui; Huo, Yong

2018-01-01

We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke. The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers ( P for linear trend=0.043). However, no such association was found in ever smokers. A test for interaction between baseline folate levels and smoking status on first stroke was significant ( P =0.045). In the total sample, folic acid therapy significantly reduced the risk of first stroke in never smokers with folate deficiency (hazard risk, 0.36; 95% confidence interval, 0.16-0.83) and in ever smokers with normal folate levels (hazard risk, 0.69; 95% confidence interval, 0.48-0.99). Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885. © 2017 American Heart Association, Inc.

A randomised controlled trial of aerobic exercise after transient ischaemic attack or minor stroke to prevent cognitive decline: the MoveIT study protocol.

PubMed

Boss, H M; Van Schaik, S M; Deijle, I A; de Melker, E C; van den Berg, B T J; Scherder, E J A; Bosboom, W M J; Weinstein, H C; Van den Berg-Vos, R M

2014-12-31

Patients with transient ischaemic attack (TIA) or stroke are at risk for cognitive impairment and dementia. Currently, there is no known effective strategy to prevent this cognitive decline. Increasing evidence exists that physical exercise is beneficial for cognitive function. However, in patients with TIA or stroke who are at risk of cognitive impairment and dementia, only a few trials have been conducted. In this study, we aim to investigate whether a physical exercise programme (MoveIT) can prevent cognitive decline in patients in the acute phase after a TIA or minor ischaemic stroke. A single-blinded randomised controlled trial will be conducted to investigate the effect of an aerobic exercise programme on cognition compared with usual care. 120 adult patients with a TIA or minor ischaemic stroke less than 1 month ago will be randomly allocated to an exercise programme consisting of a 12-week aerobic exercise programme and regular follow-up visits to a specialised physiotherapist during the period of 1 year or to usual care. Outcome measures will be assessed at the baseline, and at the 1-year and 2-year follow-up. The primary outcome is cognitive functioning measured with the Montreal Cognitive Assessment (MoCA) test and with additional neuropsychological tests. Secondary outcomes include maximal exercise capacity, self-reported physical activity and measures of secondary prevention. The study received ethical approval from the VU University Amsterdam Ethics committee (2011/383). The results of this study will be published in peer-reviewed journals and presented at international conferences. We will also disseminate the main results to our participants in a letter. The Nederlands Trial Register NTR3884. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial.

PubMed

Ohsawa, Yutaka; Hagiwara, Hiroki; Nishimatsu, Shin-Ichiro; Hirakawa, Akihiro; Kamimura, Naomi; Ohtsubo, Hideaki; Fukai, Yuta; Murakami, Tatsufumi; Koga, Yasutoshi; Goto, Yu-Ichi; Ohta, Shigeo; Sunada, Yoshihide

2018-04-17

The aim of this study was to evaluate the efficacy and safety of high-dose taurine supplementation for prevention of stroke-like episodes of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), a rare genetic disorder caused by point mutations in the mitochondrial DNA that lead to a taurine modification defect at the first anticodon nucleotide of mitochondrial tRNA Leu(UUR) , resulting in failure to decode codons accurately. After the nationwide survey of MELAS, we conducted a multicentre, open-label, phase III trial in which 10 patients with recurrent stroke-like episodes received high-dose taurine (9 g or 12 g per day) for 52 weeks. The primary endpoint was the complete prevention of stroke-like episodes during the evaluation period. The taurine modification rate of mitochondrial tRNA Leu(UUR) was measured before and after the trial. The proportion of patients who reached the primary endpoint (100% responder rate) was 60% (95% CI 26.2% to 87.8%). The 50% responder rate, that is, the number of patients achieving a 50% or greater reduction in frequency of stroke-like episodes, was 80% (95% CI 44.4% to 97.5%). Taurine reduced the annual relapse rate of stroke-like episodes from 2.22 to 0.72 (P=0.001). Five patients showed a significant increase in the taurine modification of mitochondrial tRNA Leu(UUR) from peripheral blood leukocytes (P<0.05). No severe adverse events were associated with taurine. The current study demonstrates that oral taurine supplementation can effectively reduce the recurrence of stroke-like episodes and increase taurine modification in mitochondrial tRNA Leu(UUR) in MELAS. UMIN000011908. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Patent foramen ovale closure vs medical therapy for stroke prevention: meta-analysis of randomized trials and review of heterogeneity in meta-analyses.

PubMed

Udell, Jacob A; Opotowsky, Alexander R; Khairy, Paul; Silversides, Candice K; Gladstone, David J; O'Gara, Patrick T; Landzberg, Michael J

2014-10-01

Patent foramen ovale (PFO) might be a risk factor for unexplained ("cryptogenic") stroke or transient ischemic attack (TIA). We sought to determine the efficacy and safety of transcatheter PFO closure compared with antithrombotic therapy for secondary prevention of cerebrovascular events among patients with cryptogenic stroke. We performed a systematic review and meta-analysis of MedLine and Embase (from inception to March 2013) for randomized controlled trials (RCTs) that compared transcatheter PFO closure with medical therapy in subjects with cryptogenic stroke. Data were independently extracted on trial conduct quality, baseline characteristics, efficacy, and safety events from published articles and appendices. Risk ratios (RRs) and 95% confidence intervals (CIs) for the composite of stroke or TIA, and adverse cardiovascular events including atrial fibrillation/flutter were constructed. Three RCTs of 2303 subjects with previous stroke, TIA, or systemic arterial embolism (mean age, 45.7 years; 47.3% women; mean follow-up, 2.6 years) were included. PFO closure did not significantly reduce the risk of recurrent stroke/TIA (3.7% vs 5.2%; RR, 0.73; 95% CI, 0.50-1.07; P = 0.10); however, an increased risk of incident atrial fibrillation/flutter was detected (3.8% vs 1.0%; RR, 3.67; 95% CI, 1.95-6.89; P < 0.0001). No significant heterogeneity was detected for any end point among subgroups of patients stratified according to age, sex, index cardiovascular event, device type, interatrial shunt size, and presence of an atrial septal aneurysm (all P interactions ≥ 0.09). Meta-analysis of RCTs that assessed transcatheter PFO closure for secondary prevention of cerebrovascular events in subjects with cryptogenic stroke does not demonstrate benefit compared with antithrombotic therapy, and suggests potential risks. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID-TIA): study protocol for a pilot randomised controlled trial.

PubMed

Edwards, Duncan; Fletcher, Kate; Deller, Rachel; McManus, Richard; Lasserson, Daniel; Giles, Matthew; Sims, Don; Norrie, John; McGuire, Graham; Cohn, Simon; Whittle, Fiona; Hobbs, Vikki; Weir, Christopher; Mant, Jonathan

2013-07-02

People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist--that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the reference standard. This pilot study will be used to estimate key parameters that are needed to design the main study and to estimate the accuracy of primary care diagnosis of TIA. The planned follow-on trial will have important implications for the initial management of people with suspected TIA. ISRCTN62019087.

5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials.

PubMed

Reddy, Vivek Y; Doshi, Shephal K; Kar, Saibal; Gibson, Douglas N; Price, Matthew J; Huber, Kenneth; Horton, Rodney P; Buchbinder, Maurice; Neuzil, Petr; Gordon, Nicole T; Holmes, David R

2017-12-19

The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, St. Paul, Minnesota) was equivalent to warfarin for preventing stroke in atrial fibrillation, but had a high rate of complications. In a second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), the complication rate was low. The warfarin cohort experienced an unexpectedly low ischemic stroke rate, rendering the efficacy endpoints inconclusive. However, these outcomes were based on relatively few patients followed for a relatively short time. The final results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial, are reported with patients in both trials followed for 5 years. PREVAIL and PROTECT AF are prospective randomized clinical trials with patients randomized 2:1 to LAAC or warfarin; together, they enrolled 1,114 patients for 4,343 patient-years. Analyses are by intention-to-treat, and rates are events per 100 patient-years. For the PREVAIL trial, the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority (posterior probability for noninferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve noninferiority (posterior probability for noninferiority = 97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p = 0.27), as were all-stroke/SE (HR: 0.961; p = 0.87). The ischemic stroke/SE rate was numerically higher with LAAC, but this difference did not reach statistical significance (HR: 1.71; p = 0.080). However, differences in hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding favored LAAC (HR: 0.20; p = 0.0022; HR: 0.45; p = 0.03; HR: 0.59; p = 0.027; HR: 0.73; p = 0.035; HR: 0.48; p = 0.0003, respectively). These 5-year outcomes of the PREVAIL trial, combined with the 5-year outcomes of the PROTECT AF trial, demonstrate that LAAC with Watchman provides stroke prevention in nonvalvular atrial fibrillation comparable to warfarin, with additional reductions in major bleeding, particularly hemorrhagic stroke, and mortality. (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy; NCT01182441). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Perturbation training to promote safe independent mobility post-stroke: study protocol for a randomized controlled trial.

PubMed

Mansfield, Avril; Aqui, Anthony; Centen, Andrew; Danells, Cynthia J; DePaul, Vincent G; Knorr, Svetlana; Schinkel-Ivy, Alison; Brooks, Dina; Inness, Elizabeth L; McIlroy, William E; Mochizuki, George

2015-06-06

Falls are one of the most common medical complications post-stroke. Physical exercise, particularly exercise that challenges balance, reduces the risk of falls among healthy and frail older adults. However, exercise has not proven effective for preventing falls post-stroke. Falls ultimately occur when an individual fails to recover from a loss of balance. Thus, training to specifically improve reactive balance control could prevent falls. Perturbation training aims to improve reactive balance control by repeatedly exposing participants to postural perturbations. There is emerging evidence that perturbation training reduces fall rates among individuals with neurological conditions, such as Parkinson disease. The primary aim of this work is to determine if perturbation-based balance training can reduce occurrence of falls in daily life among individuals with chronic stroke. Secondary objectives are to determine the effect of perturbation training on balance confidence and activity restriction, and functional balance and mobility. Individuals with chronic stroke will be recruited. Participants will be randomly assigned to one of two groups: 1) perturbation training, or 2) 'traditional' balance training. Perturbation training will involve both manual perturbations (e.g., a push or pull from a physiotherapist), and rapid voluntary movements to cause a loss of balance. Training will occur twice per week for 6 weeks. Participants will record falls and activity for 12 months following completion of the training program. Standardized clinical tools will be used to assess functional balance and mobility, and balance confidence before and after training. Falls are a significant problem for those with stroke. Despite the large body of work demonstrating effective interventions, such as exercise, for preventing falls in other populations, there is little evidence for interventions that prevent falls post-stroke. The proposed study will investigate a novel and promising intervention: perturbation training. If effective, this training has the potential to not only prevent falls, but to also improve safe independent mobility and engagement in daily activities for those with stroke. Current Controlled Trials: ISRCTN05434601 .

ESCAPS study protocol: a feasibility randomised controlled trial of ‘Early electrical stimulation to the wrist extensors and wrist flexors to prevent the post-stroke complications of pain and contractures in the paretic arm’

PubMed Central

Fletcher-Smith, Joanna C; Walker, Dawn-Marie; Sprigg, Nikola; James, Marilyn; Walker, Marion F; Allatt, Kate; Mehta, Rajnikant; Pandyan, Anand D

2016-01-01

Introduction Approximately 70% of patients with stroke experience impaired arm function, which is persistent and disabling for an estimated 40%. Loss of function reduces independence in daily activities and impacts on quality of life. Muscles in those who do not recover functional movement in the stroke affected arm are at risk of atrophy and contractures, which can be established as early as 6 weeks following stroke. Pain is also common. This study aims to evaluate the feasibility of a randomised controlled trial to test the efficacy and cost-effectiveness of delivering early intensive electrical stimulation (ES) to prevent post-stroke complications in the paretic upper limb. Methods and analysis This is a feasibility randomised controlled trial (n=40) with embedded qualitative studies (patient/carer interviews and therapist focus groups) and feasibility economic evaluation. Patients will be recruited from the Stroke Unit at the Nottingham University Hospitals National Health Service (NHS) Trust within 72 h after stroke. Participants will be randomised to receive usual care or usual care and early ES to the wrist flexors and extensors for 30 min twice a day, 5 days a week for 3 months. The initial treatment(s) will be delivered by an occupational therapist or physiotherapist who will then train the patient and/or their nominated carer to self-manage subsequent treatments. Ethics and dissemination This study has been granted ethical approval by the National Research Ethics Service, East Midlands Nottingham1 Research Ethics Committee (ref: 15/EM/0006). To our knowledge, this is the first study of its kind of the early application (within 72 h post-stroke) of ES to both the wrist extensors and wrist flexors of stroke survivors with upper limb impairment. The results will inform the design of a definitive randomised controlled trial. Dissemination will include 2 peer-reviewed journal publications and presentations at national conferences. Trial registration number ISRCTN1648908; Pre-results. Clinicaltrials.gov ID: NCT02324634. PMID:26729394

Interventions in the management of serum lipids for preventing stroke recurrence.

PubMed

Manktelow, B; Gillies, C; Potter, J F

2002-01-01

A close association between serum lipid levels and the incidence of coronary heart disease (CHD) has been well proven in middle aged and older persons, up to the age of 70-75 years. Individual studies have shown interventions to reduce total and low density lipoprotein (LDL) cholesterol levels, especially with 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitors (statins), to be of benefit in reducing CHD and stroke events in those with a history of coronary heart disease. However, the relation of serum cholesterol and cholesterol sub-fractions with cerebrovascular disease is less clear. It is unclear whether lipid levels in the post-stroke period are a predictor of recurrence and whether treatment to alter levels can prevent recurrence of either stroke or cardiovascular events. To investigate the effect of altering serum lipids in the prevention of cardiovascular disease and stroke recurrence in subjects with a history of stroke. The Cochrane Group Trials Register was searched up to 8 May 2001 along with MEDLINE (from 1966), EMBASE (from 1980) and the Cochrane Controlled Trials Register. All pharmaceutical firms known to produce a lipid lowering agent were also contacted and asked to provide information on publications or unpublished work relevant to this review. This review included unconfounded randomised trials of subjects aged 18 years and over with a history of stroke or Transient Ischaemic Attack (TIA). The data were extracted independently by the three reviewers. MetaView 4.1 was used for all statistical analyses. Five studies involving 1700 patients were included in the review. The active intervention in two of the studies was Clofibrate, Pravastatin in another two and Conjugated Oestrogen in the fifth. Fixed effects analysis showed no evidence of a difference in stroke recurrence between the treatment and placebo groups for those with a previous history of stroke or TIA (odds ratio 0.96, 95% confidence interval 0.71 to 1.30). In addition there was also no evidence, based on two studies, that intervention reduced the odds of all cause mortality (odds ratio 0.87, 95% confidence interval 0.55 to 1.39) nor, from one study, that there was any effect on subsequent vascular events (odds ratio 1.27, 95% confidence interval 0.84 to 1.89). These trials do not provide evidence for a benefit, or harm, from interventions to alter serum lipid levels in patients with a history solely of cerebrovascular disease. Their use, therefore, cannot yet be recommended routinely in this patient group, but ischaemic stroke patients with a history of myocardial infarction should receive statin therapy along the lines of the previous recommendations for those patients with a history of myocardial ischaemia. There are currently three ongoing trials which will recruit approximately 30,000 patients, including those with a history of stroke, and the results of these trials may have a significant effect on these conclusions.

The clinical effectiveness and cost-effectiveness of primary stroke prevention in children with sickle cell disease: a systematic review and economic evaluation.

PubMed

Cherry, M G; Greenhalgh, J; Osipenko, L; Venkatachalam, M; Boland, A; Dundar, Y; Marsh, K; Dickson, R; Rees, D C

2012-01-01

Sickle cell disease (SCD) is a recessive genetic blood disorder, caused by a mutation in the β-globin gene. For children with SCD, the risk of stroke is estimated to be up to 250 times higher than in the general childhood population. Transcranial Doppler (TCD) ultrasonography is a non-invasive technique which measures local blood velocity in the proximal portions of large intracranial arteries. Screening with TCD ultrasonography identifies individuals with high cerebral blood velocity; these children are at the highest risk of stroke. A number of primary stroke prevention strategies are currently used in clinical practice in the UK including blood transfusion, treatment with hydroxycarbamide and bone marrow transplantation (BMT). No reviews have yet assessed the clinical effectiveness and cost effectiveness of primary stroke prevention strategies in children with SCD identified to be at high risk of stroke using TCD ultrasonography. To assess the clinical effectiveness and cost-effectiveness of primary stroke prevention treatments for children with SCD who are identified (using TCD ultrasonography) to be at high risk of stroke. Electronic databases were searched from inception up to May 2011, including the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), EMBASE, the Health Technology Assessment (HTA) database, ISI Web of Science Proceedings, ISI Web of Science Citation Index, the NHS Economic Evaluation Database (NHS EED) and MEDLINE. The assessment was conducted according to accepted procedures for conducting and reporting systematic reviews and economic evaluations. A de novo Markov model was developed to determine the cost-effectiveness of TCD ultrasonography and blood transfusion, where clinically appropriate, in patients with SCD. Two randomised controlled trials met the inclusion criteria involving a study population of 209 participants. One compared blood transfusion with standard care for children who are identified as being at high risk of stroke using TCD ultrasonography. In this trial, one patient in the transfusion group had a stroke (1/63) compared with 11 children in the standard care group (11/67). The other trial assessed the impact of halting chronic transfusion in patients with SCD. Sixteen patients in the transfusion-halted group had an event (16/41) (two patients experienced stroke and 14 reverted to abnormal TCD velocity); there were no events in the continued-transfusion group (0/38). No meta-analyses of these trials were undertaken. No relevant economic evaluations were identified for inclusion in the review. The de novo modelling suggests that blood transfusions plus TCD scans (compared with just TCD scans) for patients with SCD at high risk of stroke, aged ≥ 2 years, may be good value for money. The intervention has an incremental cost-effectiveness ratio of £24,075 per quality-adjusted life-year gained, and helps avoid 68 strokes over the lifetime of a population of 1000 patients. The intervention costs an additional £13,751 per patient and generates 0.6 extra years of life in full health per patient. The data available for the economic analysis are limited. Sensitivity analyses and validation against existing data and expert opinion provide some reassurance that the conclusion of the model is reliable but further research is required to validate these findings. The main limitations relate to the availability of published clinical data; no completed randomised controlled trials were identified which evaluated the efficacy of either BMT or hydroxycarbamide for primary stroke prevention. Both the clinical and cost data available for use in the economic analysis are limited. Sensitivity analyses and validation against existing data and expert opinion provide some reassurance that the conclusions of the model are reliable, but further research is required to validate these findings. The use of TCD ultrasonography to identify children at high risk of stroke, and treating these children with prophylactic blood transfusions, appears to be both clinically effective and cost-effective compared with TCD ultrasonography only. However, given the limitations in the data available, further research is required to verify this conclusion. Several research recommendations can be proposed from this review. Clinically, more research is needed to assess the effects and optimal duration of long-term blood transfusion and the potential role of hydroxycarbamide in primary stroke prevention. From an economics perspective, further research is required to generate more robust data on which to base estimates of cost-effectiveness or against which model outputs can be calibrated. More data are required to explain how utility weights vary with age, transfusions and strokes. Research is also needed around the cost of paediatric stroke in the UK. PROSPERO CRD42011001496. The National Institute for Health Research Health Technology Assessment programme.

Intensive risk factor control in stroke prevention

PubMed Central

2013-01-01

Stroke prevention is an urgent priority because of the aging of the population and the steep association of age and risk of stroke. Direct costs of stroke are expected to more than double in the US between 2012 and 2030. By getting everything right, patients can reduce the risk of stroke by 80% or more; however, getting everything right is a tall order. Roughly in order of importance, this requires smoking cessation, maintenance of a healthy weight, a Cretan Mediterranean diet, blood pressure control, lipid-lowering drugs, appropriate use of antiplatelet agents and anticoagulants, and appropriate carotid endarterectomy and stenting. A new approach called “treating arteries instead of targeting risk factors” appears promising but requires validation in randomized trials. PMID:24167723

[Atrial fibrillation in cerebrovascular disease: national neurological perspective].

PubMed

Sargento-Freitas, Joao; Silva, Fernando; Koehler, Sebastian; Isidoro, Luís; Mendonça, Nuno; Machado, Cristina; Cordeiro, Gustavo; Cunha, Luís

2013-01-01

Cardioembolism due to atrial fibrillation assumes a dominant etiologic role in cerebrovascular diseases due to its growing incidence, high embolic risk and particular aspects of clinical events caused. Our objectives are to analyze the frequency of atrial fibrillation in patients with ischemic stroke, study the vital and functional impact of stroke due to different etiologies and evaluate antithrombotic options before and after stroke. We conducted a retrospective study including patients admitted in a central hospital due to ischemic stroke in 2010 (at least one year of follow-up). Etiology of stroke was defined using the Trial of ORG 10172 in Acute Stroke (TOAST) classification, and functional outcome by modified Rankin scale. We performed a descriptive analysis of different stroke etiologies and antithrombotic medication in patients with atrial fibrillation. We then conducted a cohort study to evaluate the clinical impact of antithrombotic options in secondary prevention after cardioembolic stroke. In our population (n = 631) we found superior frequency of cardioembolism (34.5%) to that reported in the literature. Mortality, morbidity and antithrombotic options are similar to other previous series, confirming the severity of cardioembolic strokes and the underuse of vitamin K antagonists. Oral anticoagulation was effective in secondary prevention independently from post-stroke functional condition. Despite unequivocal recommendations, oral anticoagulation is still underused in stroke prevention. This study confirms the clinical efficacy of vitamin K antagonists in secondary prevention independently from residual functional impairment.

Nurse-Led Intervention to Improve Knowledge of Medications in Survivors of Stroke or Transient Ischemic Attack: A Cluster Randomized Controlled Trial.

PubMed

Olaiya, Muideen T; Cadilhac, Dominique A; Kim, Joosup; Ung, David; Nelson, Mark R; Srikanth, Velandai K; Bladin, Christopher F; Gerraty, Richard P; Fitzgerald, Sharyn M; Phan, Thanh G; Frayne, Judith; Thrift, Amanda G

2016-01-01

Limited evidence exists on effective interventions to improve knowledge of preventive medications in patients with chronic diseases, such as stroke. We investigated the effectiveness of a nurse-led intervention, where a component was to improve knowledge of prevention medications, in patients with stroke or transient ischemic attack (TIA). Prospective sub-study of the Shared Team Approach between Nurses and Doctors for Improved Risk Factor Management, a randomized controlled trial of risk factor management. We recruited patients aged ≥18 years and hospitalized for stroke/TIA. The intervention comprised an individualized management program, involving nurse-led education, and management plan with medical specialist oversight. The outcome, participants' knowledge of secondary prevention medications at 12 months, was assessed using questionnaires. A score of ≥5 was considered as good knowledge. Effectiveness of the intervention on knowledge of medications was determined using logistic regression. Between May 2014 and January 2015, 142 consecutive participants from the main trial were included in this sub-study, 64 to usual care and 78 to the intervention (median age 68.9 years, 68% males, and 79% ischemic stroke). In multivariable analyses, we found no significant difference between intervention groups in knowledge of medications. Factors independently associated with good knowledge (score ≥5) at 12 months included higher socioeconomic position (OR 4.79, 95% CI 1.76, 13.07), greater functional ability (OR 1.69, 95% CI 1.17, 2.45), being married/living with a partner (OR 3.12, 95% CI 1.10, 8.87), and using instructions on pill bottle/package as an administration aid (OR 4.82, 95% CI 1.76, 13.22). Being aged ≥65 years was associated with poorer knowledge of medications (OR 0.24, 95% CI 0.08, 0.71), while knowledge was worse among those taking three medications (OR 0.15, 95% CI 0.03, 0.66) or ≥4 medications (OR 0.09, 95% CI 0.02, 0.44), when compared to participants taking fewer (≤2) prevention medications. There was no evidence that the nurse-led intervention was effective for improving knowledge of secondary prevention medications in patients with stroke/TIA at 12 months. However, older patients and those taking more medications should be particularly targeted for more intensive education. Australian New Zealand Clinical Trials Registry (ACTRN12688000166370).

Post-stroke dysphagia: A review and design considerations for future trials.

PubMed

Cohen, David L; Roffe, Christine; Beavan, Jessica; Blackett, Brenda; Fairfield, Carol A; Hamdy, Shaheen; Havard, Di; McFarlane, Mary; McLauglin, Carolee; Randall, Mark; Robson, Katie; Scutt, Polly; Smith, Craig; Smithard, David; Sprigg, Nikola; Warusevitane, Anushka; Watkins, Caroline; Woodhouse, Lisa; Bath, Philip M

2016-06-01

Post-stroke dysphagia (a difficulty in swallowing after a stroke) is a common and expensive complication of acute stroke and is associated with increased mortality, morbidity, and institutionalization due in part to aspiration, pneumonia, and malnutrition. Although most patients recover swallowing spontaneously, a significant minority still have dysphagia at six months. Although multiple advances have been made in the hyperacute treatment of stroke and secondary prevention, the management of dysphagia post-stroke remains a neglected area of research, and its optimal management, including diagnosis, investigation and treatment, have still to be defined. © 2016 World Stroke Organization.

Evidence-Based Carotid Interventions for Stroke Prevention: State-of-the-art Review

PubMed Central

Morris, Dylan R.; Ayabe, Kengo; Inoue, Takashi; Sakai, Nobuyuki; Bulbulia, Richard; Halliday, Alison

2017-01-01

Carotid artery stenosis is responsible for between 10–20% of all ischaemic strokes. Interventions, such as carotid end-arterectomy and carotid stenting, effectively reduce the risk of stroke in selected individuals. This review describes the history of carotid interventions, and summarises reliable evidence on the safety and efficacy of these interventions gained from large randomised clinical trials. Early trials comparing carotid endarterectomy to medical therapy alone in symptomatic patients, and asymptomatic patients, demonstrated that endarterectomy halved the risk of stroke and perioperative death in these two unique populations. The absolute risk reduction was smaller in the asymptomatic carotid trials, consistent with their lower absolute stroke risk. More recent trials in symptomatic patients, suggest that carotid stenting has similar long term durability to carotid endarterectomy, but possibly has higher procedural hazards dominated by non-disabling strokes. The Asymptomatic Carotid Surgery Trial-2, along with individual patient data meta-analysis of all asymptomatic trials, will provide reliable evidence for the choice of intervention in asymptomatic patients in whom a decision has been made for carotid revascularisation. Given improvements in effective cardiovascular medical therapy, in particular lipid-lowering medications, there is renewed uncertainty as to whether carotid interventions still provide meaningful net reductions in stroke risk in asymptomatic populations. Four large trials in Europe and the US are currently underway, and are expected to report longterm results in the next decade. It is essential that surgeons, interventionalists, and physicians continue to randomise large numbers of patients from around the world to clarify current uncertainty around the management of asymptomatic carotid stenosis. PMID:28260723

Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1

PubMed Central

Diener, Hans-Christoph; Aisenberg, James; Ansell, Jack; Atar, Dan; Breithardt, Günter; Eikelboom, John; Ezekowitz, Michael D.; Granger, Christopher B.; Halperin, Jonathan L.; Hohnloser, Stefan H.; Hylek, Elaine M.; Kirchhof, Paulus; Lane, Deirdre A.; Verheugt, Freek W.A.; Veltkamp, Roland; Lip, Gregory Y.H.

2017-01-01

Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic embolism. Today's clinician is faced with the difficult task of selecting a suitable OAC for a patient with a particular clinical profile or a particular pattern of risk factors and concomitant diseases. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. NOACs for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In the first of a two-part review, we discuss the choice of NOAC for stroke prevention in the following subgroups of patients with AF: (i) stable coronary artery disease or peripheral artery disease, including percutaneous coronary intervention with stenting and triple therapy; (ii) cardioversion, ablation and anti-arrhythmic drug therapy; (iii) mechanical valves and rheumatic valve disease, (iv) patients with time in therapeutic range of >70% on warfarin; (v) patients with a single stroke risk factor (CHA2DS2VASc score of 1 in males, 2 in females); and (vi) patients with a single first episode of paroxysmal AF. Although there are no major differences in terms of efficacy and safety between the NOACs for some clinical scenarios, in others we are able to suggest that particular drugs and/or doses be prioritized for anticoagulation. PMID:26848149

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.

PubMed

Hart, Robert G; Pearce, Lesly A; Bakheet, Majid F; Benavente, Oscar R; Conwit, Robin A; McClure, Leslie A; Talbert, Robert L; Anderson, David C

2014-04-01

Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high versus low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. Multivariable analyses of 3020 participants with recent magnetic resonance imaging-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. Prior symptomatic lacunar stroke or transient ischemic attack (TIA) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.6, 2.9), diabetes (HR 2.0, 95% CI 1.5, 2.5), black race (HR 1.7, 95% CI 1.3, 2.3), and male sex (HR 1.5, 95% CI 1.1, 1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3% per year (95% CI 3.4, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1% per year (95% CI 2.6, 3.9) in those with more than 1 of the other 3 risk factors (27% of the cohort), and 1.3% per year (95% CI 1.0, 1.7) in those with 0-1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, black race, and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk. Copyright © 2014 National Stroke Association. All rights reserved.

Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials.

PubMed

Rothwell, Peter M; Algra, Ale; Chen, Zhengming; Diener, Hans-Christoph; Norrving, Bo; Mehta, Ziyah

2016-07-23

Aspirin is recommended for secondary prevention after transient ischaemic attack (TIA) or ischaemic stroke on the basis of trials showing a 13% reduction in long-term risk of recurrent stroke. However, the risk of major stroke is very high for only the first few days after TIA and minor ischaemic stroke, and observational studies show substantially greater benefits of early medical treatment in the acute phase than do longer-term trials. We hypothesised that the short-term benefits of early aspirin have been underestimated. Pooling the individual patient data from all randomised trials of aspirin versus control in secondary prevention after TIA or ischaemic stroke, we studied the effects of aspirin on the risk and severity of recurrent stroke, stratified by the following time periods: less than 6 weeks, 6-12 weeks, and more than 12 weeks after randomisation. We compared the severity of early recurrent strokes between treatment groups with shift analysis of modified Rankin Scale (mRS) score. To understand possible mechanisms of action, we also studied the time course of the interaction between effects of aspirin and dipyridamole in secondary prevention of stroke. In a further analysis we pooled data from trials of aspirin versus control in which patients were randomised less than 48 h after major acute stroke, stratified by severity of baseline neurological deficit, to establish the very early time course of the effect of aspirin on risk of recurrent ischaemic stroke and how this differs by severity at baseline. We pooled data for 15,778 participants from 12 trials of aspirin versus control in secondary prevention. Aspirin reduced the 6 week risk of recurrent ischaemic stroke by about 60% (84 of 8452 participants in the aspirin group had an ischaemic stroke vs 175 of 7326; hazard ratio [HR] 0·42, 95% CI 0·32-0·55, p<0·0001) and disabling or fatal ischaemic stroke by about 70% (36 of 8452 vs 110 of 7326; 0·29, 0·20-0·42, p<0·0001), with greatest benefit noted in patients presenting with TIA or minor stroke (at 0-2 weeks, two of 6691 participants in the aspirin group with TIA or minor stroke had a disabling or fatal ischaemic stroke vs 23 of 5726 in the control group, HR 0·07, 95% CI 0·02-0·31, p=0·0004; at 0-6 weeks, 14 vs 60 participants, 0·19, 0·11-0·34, p<0·0001). The effect of aspirin on early recurrent ischaemic stroke was due partly to a substantial reduction in severity (mRS shift analysis odds ratio [OR] 0·42, 0·26-0·70, p=0·0007). These effects were independent of dose, patient characteristics, or aetiology of TIA or stroke. Some further reduction in risk of ischaemic stroke accrued for aspirin only versus control from 6-12 weeks, but there was no benefit after 12 weeks (stroke risk OR 0·97, 0·84-1·12, p=0·67; severity mRS shift OR 1·00, 0·77-1·29, p=0·97). By contrast, dipyridamole plus aspirin versus aspirin alone had no effect on risk or severity of recurrent ischaemic stroke within 12 weeks (OR 0·90, 95% CI 0·65-1·25, p=0·53; mRS shift OR 0·90, 0·37-1·72, p=0·99), but dipyridamole did reduce risk thereafter (0·76, 0·63-0·92, p=0·005), particularly of disabling or fatal ischaemic stroke (0·64, 0·49-0·84, p=0·0010). We pooled data for 40,531 participants from three trials of aspirin versus control in major acute stroke. The reduction in risk of recurrent ischaemic stroke at 14 days was most evident in patients with less severe baseline deficits, and was substantial by the second day after starting treatment (2-3 day HR 0·37, 95% CI 0·25-0·57, p<0·0001). Our findings confirm that medical treatment substantially reduces the risk of early recurrent stroke after TIA and minor stroke and identify aspirin as the key intervention. The considerable early benefit from aspirin warrants public education about self-administration after possible TIA. The previously unrecognised effect of aspirin on severity of early recurrent stroke, the diminishing benefit with longer-term use, and the contrasting time course of effects of dipyridamole have implications for understanding mechanisms of action. Wellcome Trust, the National Institute of Health Research (NIHR) Biomedical Research Centre, Oxford. Copyright © 2016 Rothwell et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages

PubMed Central

Weiner, Daniel E.; Dad, Taimur

2015-01-01

Summary Cerebrovascular disease and stroke are very common at all stages of chronic kidney disease (CKD), likely representing both shared risk factors as well as synergy among risk factors. More subtle ischemic brain lesions may be particularly common in the CKD population, with subtle manifestations including cognitive impairment. For individuals with nondialysis CKD, the prevention, approach to, diagnosis, and management of stroke is similar to the general, non-CKD population. For individuals with end-stage renal disease, far less is known regarding the prevention of stroke. Stroke prophylaxis using warfarin in dialysis patients with atrial fibrillation in particular remains of uncertain benefit. End-stage renal disease patients can be managed aggressively in the setting of acute stroke. Outcomes after stroke at all stages of CKD are poor, and improving these outcomes should be the subject of future clinical trials. PMID:26355250

B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial.

PubMed

2010-09-01

Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye. In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0.5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratified by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444. Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk reduction 1.56%, -0.01 to 3.16). There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups. Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins. Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, Singapore National Medical Research Council, Australia National Heart Foundation, Royal Perth Hospital Medical Research Foundation, and Health Department of Western Australia. Copyright 2010 Elsevier Ltd. All rights reserved.

RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID−TIA): study protocol for a pilot randomised controlled trial

PubMed Central

2013-01-01

Background People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist – that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? Methods/Design This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the reference standard. Discussion This pilot study will be used to estimate key parameters that are needed to design the main study and to estimate the accuracy of primary care diagnosis of TIA. The planned follow-on trial will have important implications for the initial management of people with suspected TIA. Trial registration ISRCTN62019087 PMID:23819476

Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial.

PubMed

Huo, Yong; Li, Jianping; Qin, Xianhui; Huang, Yining; Wang, Xiaobin; Gottesman, Rebecca F; Tang, Genfu; Wang, Binyan; Chen, Dafang; He, Mingli; Fu, Jia; Cai, Yefeng; Shi, Xiuli; Zhang, Yan; Cui, Yimin; Sun, Ningling; Li, Xiaoying; Cheng, Xiaoshu; Wang, Jian'an; Yang, Xinchun; Yang, Tianlun; Xiao, Chuanshi; Zhao, Gang; Dong, Qiang; Zhu, Dingliang; Wang, Xian; Ge, Junbo; Zhao, Lianyou; Hu, Dayi; Liu, Lisheng; Hou, Fan Fan

2015-04-07

Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20,702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study. Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10,348) or a tablet containing enalapril, 10 mg, alone (n = 10,354). The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels. clinicaltrials.gov Identifier: NCT00794885.

Patent foramen ovale closure versus medical therapy after cryptogenic stroke: An updated meta-analysis of all randomized clinical trials.

PubMed

Kheiri, Babikir; Abdalla, Ahmed; Osman, Mohammed; Ahmed, Sahar; Hassan, Mustafa; Bachuwa, Ghassan

2018-03-07

Cryptogenic strokes can be attributed to paradoxical emboli through patent foramen ovale (PFO). However, the effectiveness of PFO closure in preventing recurrent stroke is uncertain and the results of previous randomized clinical trials (RCTs) have been inconclusive. Hence, this study provides an updated meta-analysis of all RCTs comparing PFO closure with medical therapy for secondary prevention of cryptogenic stroke. All RCTs were identified by a comprehensive literature search of PubMed, Embase, the Cochrane Collaboration Central Register of Controlled Trials, Scopus, and Clinicaltrials.gov. The primary outcome was recurrent ischemic stroke and secondary outcomes were transient ischemic attack (TIA), all-cause mortality, new-onset atrial fibrillation (AF), serious adverse events, and major bleeding. 5 RCTs with 3440 participants were included in the present study (1829 patients underwent PFO closure and 1611 were treated medically). Pooled analysis showed a statistically significant reduction in the rate of recurrent stroke with PFO closure in comparison to medical therapy (OR 0.41; 95% CI 0.19-0.90; p = 0.03). However, there were no statistically significant reductions of recurrent TIAs (OR 0.77; 95% CI 0.51-1.14; p = 0.19) or all-cause mortality (OR 0.76; 95% CI 0.35-1.65; p = 0.48). The risk of developing new-onset AF was increased significantly with PFO closure (OR 4.74; 95% CI 2.33-9.61; p < 0.0001), but no significant differences in terms of serious adverse events or major bleeding between both groups. Patent foramen ovale closure in adults with recent cryptogenic stroke was associated with a lower rate of recurrent strokes in comparison with medical therapy alone.

Optimal Systolic Blood Pressure Levels for Primary Prevention of Stroke in General Hypertensive Adults: Findings From the CSPPT (China Stroke Primary Prevention Trial).

PubMed

Fan, Fangfang; Yuan, Ziwen; Qin, Xianhui; Li, Jianping; Zhang, Yan; Li, Youbao; Yu, Tao; Ji, Meng; Ge, Junbo; Zheng, Meili; Yang, Xinchun; Bao, Huihui; Cheng, Xiaoshu; Gu, Dongfeng; Zhao, Dong; Wang, Jiguang; Sun, Ningling; Chen, Yundai; Wang, Hong; Wang, Xiaobin; Parati, Gianfranco; Hou, Fanfan; Xu, Xiping; Wang, Xian; Zhao, Gang; Huo, Yong

2017-04-01

We aimed to investigate the relationship of time-averaged on-treatment systolic blood pressure (SBP) with the risk of first stroke in the CSPPT (China Stroke Primary Prevention Trial). A post hoc analysis was conducted using data from 17 720 hypertensive adults without cardiovascular disease, diabetes mellitus, and renal function decline from the CSPPT, a randomized double-blind controlled trial. The primary outcome was first stroke. Over a median follow-up duration of 4.5 years, the association between averaged on-treatment SBP and risk for first stoke followed a U-shape curve, with increased risk above and below the reference range of 120 to 130 mm Hg. Compared with participants with time-averaged on-treatment SBP at 120 to 130 mm Hg (mean, 126.2 mm Hg), the risk of first stroke was not only increased in participants with SBP at 130 to 135 mm Hg (mean, 132.6 mm Hg; 1.5% versus 0.8%; hazard ratio, 1.63; 95% confidence interval, 1.01-2.63) or 135 to 140 mm Hg (mean, 137.5 mm Hg; 1.9% versus 0.8%; hazard ratio, 1.85; 95% confidence interval, 1.17-2.93), but also increased in participants with SBP <120 mm Hg (mean, 116.7 mm Hg; 3.1% versus 0.8%; hazard ratio, 4.37; 95% confidence interval, 2.10-9.07). Similar results were found in various subgroups stratified by age, sex, and treatment group. Furthermore, lower diastolic blood pressure was associated with lower risk of stroke, with a plateau at a time-average on-treatment diastolic blood pressure <80 mm Hg. In conclusion, among adults with hypertension and without a history of stroke or myocardial infarction, diabetes mellitus, or renal function decline, a lower SBP goal of 120 to 130 mm Hg, as compared with a target SBP of 130 to 140 mm Hg or <120 mm Hg, resulted in the lowest risk of first stroke. © 2017 American Heart Association, Inc.

Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE-AF) randomized trial: Design and rationale.

PubMed

Bernstein, Richard A; Kamel, Hooman; Granger, Christopher B; Kowal, Robert C; Ziegler, Paul D; Schwamm, Lee H

2017-08-01

Approximately 20% of ischemic strokes are associated with clinically apparent atrial fibrillation (AF). Regardless of stroke etiology, detection of AF in patients with ischemic strokes often changes antithrombotic treatment from anti-platelet to oral anticoagulation therapy. The role and the optimum duration of cardiac monitoring to detect AF in patients with strokes presumed due to large vessel atherosclerosis or small vessel disease is unknown. This manuscript describes the design and rationale of the STROKE-AF trial. STROKE-AF is a randomized, controlled, open-label, post-market clinical trial. Detection of AF will be evaluated using continuous arrhythmia monitoring with an insertable cardiac monitor (ICM) compared with standard of care follow-up in patients with stroke (within the prior 10 days) that is presumed due to large vessel cervical or intracranial atherosclerosis, or to small vessel disease. Approximately 500 patients will be enrolled at approximately 40 centers in the United States. Patients will be randomized 1:1 to arrhythmia monitoring with an ICM (continuous monitoring arm) or standard of care follow-up (control arm). Subjects will be followed for ≥12 months and up to 3 years. The primary objective is to compare the incidence rate of detected AF through 12 months of follow-up between the two arms. This trial will provide information on the value of ICMs to detect subclinical AF in patients with stroke presumed due to large vessel atherosclerosis or small vessel disease, which will have implications for guiding treatment with oral anticoagulation for secondary stroke prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: Secondary Prevention of Small Subcortical Strokes (SPS3) trial

PubMed Central

Hart, Robert G.; Pearce, Lesly A.; Bakheet, Majid F.; Benavente, Oscar; Conwit, Robin A.; McClure, Leslie A.; Talbert, Robert L.; Anderson, David C.

2013-01-01

Background Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high vs. low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. Methods Multivariable analyses of 3020 participants with recent MRI-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. Results: Prior symptomatic lacunar stroke or TIA (HR 2.2, 95%CI 1.6,2.9), diabetes (HR 2.0, 95%CI 1.5,2.5), Black race (HR 1.7, 95%CI 1.3,2.3) and male sex (HR 1.5, 95%CI 1.1,1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3%/yr (95% CI 3.3, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1%/yr (95%CI 2.6, 3.9) in those with >1 of the other 3 risk factors (27% of the cohort), and 1.3%/yr (95%CI 1.0,1.7) in those with 0 to 1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. Conclusions In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, Black race and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk. PMID:23800503

Risk of recurrent stroke in patients with silent brain infarction in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) imaging substudy.

PubMed

Weber, Ralph; Weimar, Christian; Wanke, Isabel; Möller-Hartmann, Claudia; Gizewski, Elke R; Blatchford, Jon; Hermansson, Karin; Demchuk, Andrew M; Forsting, Michael; Sacco, Ralph L; Saver, Jeffrey L; Warach, Steven; Diener, Hans Christoph; Diehl, Anke

2012-02-01

Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent noncardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality. The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age- and sex-matched patients with stroke without SBI. Secondary outcomes were a combined vascular end point, other vascular events, and mortality. The 2 groups were compared using conditional logistic regression. Silent brain infarction was detected in 207 (20.4%) of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (OR, 1.42; 95% CI, 0.79-2.56; P=0.24) during a mean follow-up of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI. The presence of SBI in patients with recent mild noncardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality rate. URL: http://clinicaltrials.gov. Unique identifier: NCT00153062.

Quality of life after lacunar stroke: the Secondary Prevention of Small Subcortical Strokes study.

PubMed

Dhamoon, Mandip S; McClure, Leslie A; White, Carole L; Lau, Helena; Benavente, Oscar; Elkind, Mitchell S V

2014-01-01

We sought to describe the course and predictors of quality of life (QOL) after lacunar stroke. We hypothesized that there is a decline in QOL after recovery from lacunar stroke. The Secondary Prevention of Small Subcortical Strokes is a clinical trial in lacunar stroke patients with annual assessments of QOL with the stroke-specific QOL score. The overall score was used and analyzed as a continuous variable (range 0-5). We fit linear mixed models to assess the trend in QOL over time, assuming linearity of time, and adjusted for demographics, medical risk factors, cognitive factors, and functional status in univariable and multivariable models. Among 2870 participants, mean age was 63.4 years (SD 10.7), 63% were men, 51% White, 32% Hispanic, 36% had college education, 36% had diabetes, 89% had hypertension, and 10% had prior stroke. Mean poststroke Barthel Index (BI) score was 95.4 (assessed on average 6 months after stroke). In the final multivariable model, there was an average increase in QOL of .6% per year, and factors associated with decline in QOL over time included age (-.0003 per year, P < .0001), any college education (-.0013 per year, .01), prior stroke (-.004 per year, P < .0001), and BI (-.0002 per year, P < .0001). In this clinical trial of lacunar stroke patients, there was a slight annual increase in QOL overall, and age, level of education, and prior stroke were associated with changes in QOL over time. Multiple strokes may cause decline in QOL over time in the absence of recurrent events. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Rationale and Study Design for a Single-Arm Phase IIa Study Investigating Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning

PubMed Central

Liu, Shi-Meng; Zhao, Wen-Le; Song, Hai-Qing; Meng, Ran; Li, Si-Jie; Ren, Chang-Hong; Ovbiagele, Bruce; Ji, Xun-Ming; Feng, Wu-Wei

2018-01-01

Background: Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA. Methods: This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes. Conclusions: The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA. Trial Registration: ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820. PMID:29363651

Efficacy of Chinese herbal medicine for stroke modifiable risk factors: a systematic review.

PubMed

Peng, Wenbo; Lauche, Romy; Ferguson, Caleb; Frawley, Jane; Adams, Jon; Sibbritt, David

2017-01-01

The vast majority of stroke burden is attributable to its modifiable risk factors. This paper aimed to systematically summarise the evidence of Chinese herbal medicine (CHM) interventions on stroke modifiable risk factors for stroke prevention. A literature search was conducted via the MEDLINE, CINAHL/EBSCO, SCOPUS, and Cochrane Database from 1996 to 2016. Randomised controlled trials or cross-over studies were included. Risk of bias was assessed according to the Cochrane Risk of Bias tool. A total of 46 trials (6895 participants) were identified regarding the use of CHM interventions in the management of stroke risk factors, including 12 trials for hypertension, 10 trials for diabetes, eight trials for hyperlipidemia, seven trials for impaired glucose tolerance, three trials for obesity, and six trials for combined risk factors. Amongst the included trials with diverse study design, an intervention of CHM as a supplement to biomedicine and/or a lifestyle intervention was found to be more effective in lowering blood pressure, decreasing blood glucose level, helping impaired glucose tolerance reverse to normal, and/or reducing body weight compared to CHM monotherapy. While no trial reported deaths amongst the CHM groups, some papers do report moderate adverse effects associated with CHM use. However, the findings of such beneficial effects of CHM should be interpreted with caution due to the heterogeneous set of complex CHM studied, the various control interventions employed, the use of different participants' inclusion criteria, and low methodological quality across the published studies. The risk of bias of trials identified was largely unclear in the domains of selection bias and detection bias across the included studies. This study showed substantial evidence of varied CHM interventions improving the stroke modifiable risk factors. More rigorous research examining the use of CHM products for sole or multiple major stroke risk factors are warranted.

Vorapaxar in atherosclerotic disease management.

PubMed

Cheng, Judy W M; Colucci, Vincent; Howard, Patricia A; Nappi, Jean M; Spinler, Sarah A

2015-05-01

To review the pharmacology, efficacy, and safety of vorapaxar, a protease activator receptor-1 (PAR-1) antagonist, in the management of atherosclerotic diseases. Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist. A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions). Two phase III clinical trials with vorapaxar have been published. In patients with non-ST segment elevation myocardial infarction (MI), vorapaxar failed to significantly reduce the primary efficacy end point (composite of cardiovascular death, MI, stroke, recurrent ischemia with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for patients with cardiovascular disease, the composite end point of cardiovascular death, MI, or stroke was significantly reduced. In both trials, the safety end points of major/minor bleeding were increased compared with placebo. In the secondary prevention trial, an increased incidence of intracranial hemorrhage led to the exclusion of patients with a prior history of stroke. Vorapaxar is approved for use with aspirin and/or clopidogrel in the secondary prevention of cardiovascular events in stable patients with peripheral arterial disease or a history of MI. However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of bleeding. It is, therefore, essential to balance the need for further reduction of risk of thrombotic event with patient's individual bleeding risk. © The Author(s) 2015.

Blood pressure after recent stroke: baseline findings from the secondary prevention of small subcortical strokes trial.

PubMed

White, Carole L; Pergola, Pablo E; Szychowski, Jeff M; Talbert, Robert; Cervantes-Arriaga, Amin; Clark, Heather D; Del Brutto, Oscar H; Godoy, Ivan Esteban; Hill, Michael D; Pelegrí, Antoni; Sussman, Craig R; Taylor, Addison A; Valdivia, José; Anderson, Dave C; Conwit, Robin; Benavente, Oscar R

2013-09-01

Hypertension is the most powerful risk factor for stroke. The aim of this study was to characterize baseline blood pressure in participants in the Secondary Prevention of Small Subcortical Strokes trial. For this cross-sectional analysis, participants were categorized by baseline systolic blood pressure (SBP) < 120, 120-139, 140-159, 160-179, and ≥ 180 mm Hg and compared on demographic and clinical characteristics. Predictors of SBP < 140 mm Hg were examined. Mean SBP was 143±19 mm Hg while receiving an average of 1.7 antihypertensive medications; SBP ≥ 140 mm Hg for 53% and ≥ 160 mm Hg for 18% of the 3,020 participants. Higher SBP was associated with a history of hypertension and hypertension for longer duration (both P < 0.0001). Higher SBPs were associated with more extensive white matter disease on magnetic resonance imaging (P < 0.0001). There were significant differences in entry-level SBP when participants were categorized by race and region (both P < 0.0001). Black participants were more likely to have SBP ≥ 140 mm Hg. Multivariable logistic regression showed an independent effect for region with those from Canada more likely (odds ratio = 1.7; 95% confidence interval, 1.29, 2.32) to have SBP < 140 mm Hg compared with participants from United States. In this cohort with symptomatic lacunar stroke, more than half had uncontrolled hypertension at approximately 2.5 months after stroke. Regional, racial, and clinical differences should be considered to improve control and prevent recurrent stroke.

Ximelagatran compared with warfarin for the prevention of systemic embolism and stroke. An imputed placebo analysis.

PubMed

Berry, Colin; Norrie, John; McMurray, John J V

2005-03-01

The active control trials, SPORTIF III and SPORTIF V, compared the direct thrombin inhibitor ximelagatran to warfarin, where each was given as a treatment to prevent systemic embolism and stroke in patients with atrial fibrillation. Because warfarin has previously been compared to placebo in similar patients and ximelagatran has now been compared to warfarin, an indirect comparison between ximelagatran and placebo is possible (imputed placebo analysis). In this analysis, ximelagatran reduces the risk of stroke and systemic embolism by 66% (hazard ratio 0.338; 95% confidence interval [CI] 0.204-0.560). Ximelagatran preserves 102% (95% CI 72-132%) of the benefit of warfarin. Based on these data, ximelagatran may be an effective alternative to warfarin for the prevention of stroke and systemic embolism in high-risk patients with atrial fibrillation.

Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study.

PubMed

Diener, Hans-Christoph; Sacco, Ralph L; Yusuf, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-10-01

The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062. 20,332 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups. Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.

Prevention of Thromboembolism in Atrial Fibrillation

PubMed Central

Segal, Jodi B; McNamara, Robert L; Miller, Marlene R; Kim, Nina; Goodman, Steven N; Powe, Neil R; Robinson, Karen A; Bass, Eric B

2000-01-01

OBJECTIVE Appropriate use of drugs to prevent thromboembolism in patients with atrial fibrillation (AF) involves comparing the patient's risk of stroke and risk of hemorrhage. This review summarizes the evidence regarding the efficacy of these medications. METHODS We conducted a meta-analysis of randomized controlled trials of drugs used to prevent thromboembolism in adults with nonpostoperative AF. Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until May 1998. MAIN RESULTS Eleven articles met criteria for inclusion in this review. Warfarin was more efficacious than placebo for primary stroke prevention (aggregate odds ratio [OR] of stroke =0.30, 95% confidence interval [CI] 0.19, 0.48), with moderate evidence of more major bleeding (OR 1.90; 95% CI 0.89, 4.04). Aspirin was inconclusively more efficacious than placebo for stroke prevention (OR 0.56, 95% CI 0.19, 1.65), with inconclusive evidence regarding more major bleeds (OR 0.81, 95% CI 0.37, 1.77). For primary prevention, assuming a baseline risk of 45 strokes per 1,000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was evidence suggesting fewer strokes among patients on warfarin than among patients on aspirin (aggregate OR 0.64, 95% CI 0.43, 0.96), with only suggestive evidence for more major hemorrhage (OR 1.60, 95% CI 0.77,3.35). However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared with aspirin was low (5.5 per 1,000 person-years) compared with an older group (15 per 1,000 person-years). CONCLUSION In general, the evidence strongly supports warfarin for patients with AF at average or greater risk of stroke. Aspirin may prove to be useful in subgroups with a low risk of stroke, although this is not definitively supported by the evidence. PMID:10632835

Baseline feature of a randomized trial assessing the effects of disease management programs for the prevention of recurrent ischemic stroke.

PubMed

Fukuoka, Yasuko; Hosomi, Naohisa; Hyakuta, Takeshi; Omori, Toyonori; Ito, Yasuhiro; Uemura, Jyunichi; Kimura, Kazumi; Matsumoto, Masayasu; Moriyama, Michiko

2015-03-01

Comprehensive and long-term patient education programs designed to improve self-management can help patients better manage their medical condition. Using disease management programs (DMPs) that were created for each of the risk factor according to clinical practice guidelines, we evaluate their influence on the prevention of stroke recurrence. This is a randomized study conducted with ischemic stroke patients within 1 year from their onset. Subjects in the intervention group received a 6-month DMPs that included self-management education provided by a nurse along with support in collaboration with the primary care physician. Those in the usual care group received ordinary outpatient care. The primary end points are stroke recurrence and stroke death. Patients were enrolled for 2 years with plans for a 2-year follow-up after the 6-month education period (total of 30 months). A total of 321 eligible subjects (average age, 67.3 years; females, 96 [29.9%]), including 21 subjects (6.5%) with transient ischemic attack, were enrolled in this study. Regarding risk factors for stroke, 260 subjects (81.0%) had hypertension, 249 subjects (77.6%) had dyslipidemia, 102 subjects (31.8%) had diabetes mellitus, 47 subjects (14.6%) had atrial fibrillation, and 98 subjects (30.5%) had chronic kidney disease. There were no significant differences between the 2 groups with respect to subject characteristics. This article describes the rationale, design, and baseline features of a randomized controlled trial that aimed to assess the effects of DMPs for the secondary prevention of stroke. Subject follow-up is in progress and will end in 2015. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Comparative Effectiveness of Blood Pressure-lowering Drugs in Patients who have Already Suffered From Stroke

PubMed Central

Wang, Wei-Ting; You, Li-Kai; Chiang, Chern-En; Sung, Shih-Hsien; Chuang, Shao-Yuan; Cheng, Hao-Min; Chen, Chen-Huan

2016-01-01

Abstract Hypertension is the most important risk factor for stroke and stroke recurrence. However, the preferred blood pressure (BP)-lowering drug class for patients who have suffered from a stroke has yet to be determined. To investigate the relative effects of BP-lowering therapies [angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blockers (ARB), β blockers, calcium channel blockers (CCBs), diuretics, and combinations of these drugs] in patients with a prior stroke history, we performed a systematic review and meta-analysis using both traditional frequentist and Bayesian random-effects models and meta-regression of randomized controlled trials (RCTs) on the outcomes of recurrent stroke, coronary heart disease (CHD), and any major adverse cardiac and cerebrovascular events (MACCE). Trials were identified from searches of published hypertension guidelines, electronic databases, and previous systematic reviews. Fifteen RCTs composed of 39,329 participants with previous stroke were identified. Compared with the placebo, only ACEI along with diuretics significantly reduced recurrent stroke events [odds ratio (OR) = 0.54, 95% credibility interval (95% CI) 0.33–0.90]. On the basis of the distribution of posterior probabilities, the treatment ranking consistently identified ACEI along with diuretics as the preferred BP-lowering strategy for the reduction of recurrent stroke and CHD (31% and 35%, respectively). For preventing MACCE, diuretics appeared to be the preferred agent for stroke survivors (34%). Moreover, the meta-regression analysis failed to demonstrate a statistical significance between BP reduction and all outcomes (P = 0.1618 for total stroke, 0.4933 for CHD, and 0.2411 for MACCE). Evidence from RCTs supports the use of diuretics-based treatment, especially when combined with ACEI, for the secondary prevention of recurrent stroke and any vascular events in patients who have suffered from stroke. PMID:27082571

Coronary heart disease risk in patients with stroke or transient ischemic attack and no known coronary heart disease: findings from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.

PubMed

Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Benavente, Oscar; Zweifler, Richard M; Callahan, Alfred; Hennerici, Michael G; Zivin, Justin A; Welch, K Michael A

2010-03-01

Noncoronary forms of atherosclerosis (including transient ischemic attacks or stroke of carotid origin or >50% stenosis of the carotid artery) are associated with a 10-year vascular risk of >20% and are considered as a coronary heart disease (CHD) -risk equivalent from the standpoint of lipid management. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial included patients with stroke or transient ischemic attack and no known CHD regardless of the presence of carotid atherosclerosis. We evaluated the risk of developing clinically recognized CHD in SPARCL patients. A total of 4731 patients (mean age, 63 years) was randomized to 80 mg/day atorvastatin placebo. The rates of major coronary event, any CHD event, and any revascularization procedure were evaluated. After 4.9 years of follow-up, the risks of a major coronary event and of any CHD end point in the placebo group were 5.1% and 8.6%, respectively. The rate of outcome of stroke decreased over time, whereas the major coronary event rate was stable. Relative to those having a large vessel-related stroke at baseline, those having a transient ischemic attack, hemorrhagic stroke, small vessel stroke, or a stroke of unknown cause had similar absolute rates for a first major coronary event and for any CHD event; transient ischemic attack, small vessel, and unknown cause groups had lower absolute revascularization procedure rates. Major coronary event, any CHD event, and any revascularization procedure rates were similarly reduced in all baseline stroke subtypes in the atorvastatin arm compared with placebo with no heterogeneity between groups. CHD risk can be substantially reduced by atorvastatin therapy in patients with recent stroke or transient ischemic attack regardless of stroke subtype.

Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts.

PubMed

Piccini, Jonathan P; Stevens, Susanna R; Chang, YuChiao; Singer, Daniel E; Lokhnygina, Yuliya; Go, Alan S; Patel, Manesh R; Mahaffey, Kenneth W; Halperin, Jonathan L; Breithardt, Günter; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Fox, Keith A A; Califf, Robert M

2013-01-15

We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial. In ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), 14 264 patients with nonvalvular AF and creatinine clearance ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R(2)CHADS(2)) improved net reclassification index by 6.2% compared with CHA(2)DS(2)VASc (C statistic=0.578) and by 8.2% compared with CHADS(2) (C statistic=0.575). The inclusion of creatinine clearance <60 mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590.Validation of R(2)CHADS(2) in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%-22.5%) relative to CHADS(2). In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00403767.

Acupuncture lowering blood pressure for secondary prevention of stroke: a study protocol for a multicenter randomized controlled trial.

PubMed

Du, Yu-Zheng; Gao, Xin-Xin; Wang, Cheng-Ting; Zheng, Hai-Zhen; Lei, Yun; Wu, Meng-Han; Shi, Xue-Min; Ban, Hai-Peng; Gu, Wen-Long; Meng, Xiang-Gang; Wei, Mao-Ti; Hu, Chun-Xiao

2017-09-15

Stroke is the prime cause of morbidity and mortality in the general population, and hypertension will increase the recurrence and mortality of stroke. We report a protocol of a pragmatic randomized controlled trial (RCT) using blood pressure (BP)-lowering acupuncture add-on treatment to treat patients with hypertension and stroke. This is a large-scale, multicenter, subject-, assessor- and analyst-blinded, pragmatic RCT. A total of 480 patients with hypertension and ischemic stroke will be randomly assigned to two groups: an experimental group and a control group. The experimental group will receive "HuoXueSanFeng" acupuncture combined with one antihypertensive medication in addition to routine ischemic stroke treatment. The control group will only receive one antihypertensive medication and basic treatments for ischemic stroke. HuoXueSanFeng acupuncture will be given for six sessions weekly for the first 6 weeks and three times weekly for the next 6 weeks. A 9-month follow-up will, thereafter, be conducted. Antihypertensive medication will be adjusted based on BP levels. The primary outcome will be the recurrence of stroke. The secondary outcomes including 24-h ambulatory BP, the TCM syndrome score, the Short Form 36-item Health Survey (SF-36), the National Institute of Health Stroke Scale (NIHSS), as well as the Barthel Index (BI) scale will be assessed at baseline, 6 weeks and 12 weeks post initiating treatments; cardiac ultrasound, carotid artery ultrasound, transcranial Doppler, and lower extremity ultrasound will be evaluated at baseline and 12 weeks after treatment. The safety of acupuncture will also be assessed. We aim to determine the clinical effects of controlling BP for secondary prevention of stroke with acupuncture add-on treatment. ClinicalTrials.gov, ID: NCT02967484 . Registered on 13 February 2017; last updated on 27 June 2017.

Patent Foramen Ovale Closure in the Setting of Cryptogenic Stroke: A Meta-Analysis of Five Randomized Trials.

PubMed

Garg, Lohit; Haleem, Affan; Varade, Shweta; Sivakumar, Keithan; Shah, Mahek; Patel, Brijesh; Agarwal, Manyoo; Agrawal, Sahil; Leary, Megan; Kluck, Bryan

2018-05-24

The clinical benefit of patent foramen ovale (PFO) closure after cryptogenic stroke has been a topic of debate for decades. Recently, 3 randomized controlled trials of PFO closure in patients with cryptogenic stroke demonstrated a significantly reduced risk of recurrent stroke compared with standard medical therapy alone. This meta-analysis was performed to clarify the efficacy of PFO closure for future stroke prevention in this population. A systematic literature search was undertaken. Published pooled data from 5 large randomized clinical trials (CLOSE, RESPECT, Gore REDUCE, CLOSURE I, and PC) were combined and then subsequently analyzed. Enrolled patients with cryptogenic stroke were assigned to receive standard medical care or to undergo endovascular PFO closure, with a primary outcome of reduction in stroke recurrence rate. Secondary outcomes included rates of transient ischemic attack (TIA), composite outcome of stroke, TIA, and death from all causes, and rates of atrial fibrillation events. We analyzed data for 3412 patients. Transcatheter PFO closure resulted in a statistically significant reduced rate of recurrent stroke, compared with medication alone. Patients undergoing closure were 58% less likely to have another stroke. The number needed to treat with PFO closure to reduce recurrent stroke for 1 patient was 40. Endovascular PFO closure was associated with a reduced risk of recurrent stroke in patients with a prior cryptogenic cerebral infarct. Although the absolute stroke reduction was small, these findings are clinically significant, given the young age of this patient population and the patients' lifetime risk of recurrent stroke. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

PubMed Central

2011-01-01

Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011). Trial Registration Trial listed in ClinicalTrials.gov as NCT00166257 and sponsored by AGA Medical, Plymouth, MN, USA PMID:21356042

Rivaroxaban as an oral anticoagulant for stroke prevention in atrial fibrillation

PubMed Central

Turpie, Alexander GG

2014-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed world and is associated with a fivefold increase in the risk of stroke, accounting for up to 15% of strokes in the general population. The European Society of Cardiology now recommends direct oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran, in preference to vitamin K antagonist therapy for the prevention of stroke in patients with A F. This review focuses on the direct Factor Xa inhibitor rivaroxaban, summarizing the properties that make rivaroxaban appropriate for anticoagulant therapy in this indication (including its predictable pharmacokinetic and pharmacodynamic profile and once-daily dosing regimen) and describing data from the Phase III ROCKET AF trial, which showed once-daily rivaroxaban to be noninferior to warfarin for the prevention of stroke in patients with nonvalvular AF. In this trial, similar rates of major and nonmajor clinically relevant bleeding were observed; however, when compared with warfarin, rivaroxaban was associated with clinically significant reductions in intracranial and fatal bleeding. On the basis of these results, rivaroxaban was approved in both the United States and the European Union for the prevention of stroke and systemic embolism in patients with nonvalvular AF. Subanalyses of ROCKET AF data showed rivaroxaban to have consistent efficacy and safety across a wide range of patients, and studies to confirm these results in real-world settings are underway. This review also describes practical considerations for treatment with rivaroxaban in clinical practice (including dose reductions in specific high-risk patients, eg, those with renal impairment), recommendations for the transition from vitamin K antagonists to rivaroxaban, the management of bleeding events, and the measurement of rivaroxaban exposure. PMID:24711702

Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force.

PubMed

Hayden, Michael; Pignone, Michael; Phillips, Christopher; Mulrow, Cynthia

2002-01-15

The use of aspirin to prevent cardiovascular disease events in patients without a history of cardiovascular disease is controversial. To examine the benefits and harms of aspirin chemoprevention. MEDLINE (1966 to May 2001). 1) Randomized trials at least 1 year in duration that examined aspirin chemoprevention in patients without previously known cardiovascular disease and 2) systematic reviews, recent trials, and observational studies that examined rates of hemorrhagic strokes and gastrointestinal bleeding secondary to aspirin use. One reviewer read and extracted data from each included article and constructed evidence tables. A second reviewer checked the accuracy of the data extraction. Discrepancies were resolved by consensus. Meta-analysis was performed, and the quantitative results of the review were then used to model the consequences of treating patients with different levels of baseline risk for coronary heart disease. Five trials examined the effect of aspirin on cardiovascular events in patients with no previous cardiovascular disease. For patients similar to those enrolled in the trials, aspirin reduces the risk for the combined end point of nonfatal myocardial infarction and fatal coronary heart disease (summary odds ratio, 0.72 [95% CI, 0.60 to 0.87]). Aspirin increased the risk for hemorrhagic strokes (summary odds ratio, 1.4 [CI, 0.9 to 2.0]) and major gastrointestinal bleeding (summary odds ratio, 1.7 [CI, 1.4 to 2.1]). All-cause mortality (summary odds ratio, 0.93 [CI, 0.84 to 1.02]) was not significantly affected. For 1000 patients with a 5% risk for coronary heart disease events over 5 years, aspirin would prevent 6 to 20 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. For patients with a risk of 1% over 5 years, aspirin would prevent 1 to 4 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. The net benefit of aspirin increases with increasing cardiovascular risk. In the decision to use aspirin chemoprevention, the patient's cardiovascular risk and relative utility for the different clinical outcomes prevented or caused by aspirin use must be considered.

Prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial.

PubMed

Belgaid, Djouhar Roufeida; Khan, Zara; Zaidi, Mariam; Hobbs, Adrian

2016-09-15

Assessing the safety and effectiveness of left atrial appendage (LAA) (pouch found in the upper chambers of the heart) occlusion, using the Watchman device compared to long term warfarin therapy (drug that reduces clot formation), in preventing the risk of stroke in patients with atrial fibrillation (most common type of irregular heart beat). 90% of strokes in atrial fibrillation arise from clots forming in this pouch. By mechanically blocking it using the device less clots are suggested to be formed. This is an alternative to taking warfarin especially in patients who cannot take it. 50 sites in the United States enrolled 407 participants. After being randomly allocated, the device group had 269 participants and warfarin group (comparator)had 138 participants. Patients with atrial fibrillation and at high risk of stroke were randomly allocated a group after they were deemed eligible. Patients in the device group had to take warfarin and aspirin for 45days till the complete closure of the LAA. The oral anticoagulant was followed by dual antiplatelet therapy until 6months and then ASA. Patients in the warfarin group have to take it for life and were continually monitored. The study ran for 26months. The trial assessed the rate of adverse events using three endpoints: The PREVAIL trial was not designed to show superiority, but non-inferiority. It met the safety endpoint and one efficacy endpoint for the watchman device compared to long term warfarin for overall efficacy of the device. The results established that LAA occlusion is not worse than warfarin intake for the prevention of stroke more than 1week after randomization. Compared to previous trials, the safety of the device has also improved. LAA occlusion is a reasonable alternative to chronic warfarin therapy in stroke prevention for patients with atrial fibrillation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Presentation and outcomes of "wake-up strokes" in a large randomized stroke trial: analysis of data from the International Stroke Trial.

PubMed

Moradiya, Yogesh; Janjua, Nazli

2013-11-01

Recent studies comparing the outcomes of wake-up stroke (WUS) and stroke while awake (SWA) patients reveal better outcomes among SWA patients, attributable in part to their higher rates of thrombolysis. Patients with WUS are largely excluded from therapy. Earlier analyses, conducted before the approval of alteplase for acute stroke, show the true divergence of natural histories between these 2 groups. We analyzed 17,398 patients with ischemic stroke from the International Stroke Trial and compared both presentations and outcomes between the WUS and SWA groups. Severity was assessed by level of consciousness, Oxfordshire Community Stroke Project (OCSP) stroke classification, number of neurologic deficits, and predicted probability of dependency or death. Outcomes were assessed at day 14 and at 6 months. Outcome assessments were controlled for potential confounders. WUS represented 29.6% of all ischemic strokes. More severe OSCP stroke type (total anterior circulation syndrome) was less common in WUS. Although more patients with WUS were alert at presentation with a lower predicted probability of dependency, the 14-day mortality rates and rates of poor outcome at 6 months were similar between the 2 groups. WUS patients comprise one quarter to one third of ischemic stroke patients. Despite their more benign presentations, they deteriorate to outcome rates similar to SWA. Although they are typically excluded from time-dependent acute interventions, patients with WUS may benefit from acute intervention to prevent this worsening natural history. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation for the secondary prevention of stroke: a subgroup analysis of J-ROCKET AF.

PubMed

Tanahashi, Norio; Hori, Masatsugu; Matsumoto, Masayasu; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

2013-11-01

The overall analysis of the rivaroxaban versus warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial revealed that rivaroxaban was not inferior to warfarin with respect to the primary safety outcome. In addition, there was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban compared with warfarin. In this subanalysis of the J-ROCKET AF trial, we investigated the consistency of safety and efficacy profile of rivaroxaban versus warfarin among the subgroups of patients with previous stroke, transient ischemic attack, or non-central nervous system systemic embolism (secondary prevention group) and those without (primary prevention group). Patients in the secondary prevention group were 63.6% of the overall population of J-ROCKET AF. In the secondary prevention group, the rate of the principal safety outcome (% per year) was 17.02 in rivaroxaban-treated patients and 18.26 in warfarin-treated patients (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.70-1.29), while the rate of the primary efficacy endpoint was 1.66 in rivaroxaban-treated patients and 3.25 in warfarin-treated patients (HR 0.51; 95% CI 0.23-1.14). There were no significant interactions in the principal safety and the primary efficacy endpoints of rivaroxaban compared to warfarin between the primary and secondary prevention groups (P=.090 and .776 for both interactions, respectively). The safety and efficacy profile of rivaroxaban compared with warfarin was consistent among patients in the primary prevention group and those in the secondary prevention group. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A noninferiority confirmatory trial of prasugrel versus clopidogrel in Japanese patients with non-cardioembolic stroke: rationale and study design for a randomized controlled trial - PRASTRO-I trial.

PubMed

Nagao, Takehiko; Toyoda, Kazunori; Kitagawa, Kazuo; Kitazono, Takanari; Yamagami, Hiroshi; Uchiyama, Shinichiro; Tanahashi, Norio; Matsumoto, Masayasu; Minematsu, Kazuo; Nagata, Izumi; Nishikawa, Masakatsu; Nanto, Shinsuke; Abe, Kenji; Ikeda, Yasuo; Ogawa, Akira

2018-04-01

This comparison of PRAsugrel and clopidogrel in Japanese patients with ischemic STROke (PRASTRO)-I trial investigates the noninferiority of prasugrel to clopidogrel sulfate in the prevention of recurrence of primary events (ischemic stroke, myocardial infarction, and death from other vascular causes), and the long-term safety of prasugrel in Japanese patients with non-cardioembolic stroke. This was an active-controlled, randomized, double-blind, double-dummy, parallel-group study conducted between July 2011 and March 2016 at multiple centers around Japan. Patients had to meet eligibility criteria before receiving 3.75 mg prasugrel or 75 mg clopidogrel orally once daily for a period of 96-104 weeks. A total of 3747 patients were included in this trial; 1598 in the 3.75 mg prasugrel group and 1551 in the 75 mg clopidogrel group completed the study. During the study period, 287 (15.2%) patients in the prasugrel group and 311 (16.7%) in the clopidogrel group discontinued treatment. Baseline characteristics, safety, and efficacy results are forthcoming and will be published separately. This article presents the study design and rationale for a trial investigating the noninferiority of prasugrel to clopidogrel sulfate with regards to the inhibitory effect on primary events in patients with non-cardioembolic stroke.

Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

PubMed

Smith, Eric E; Saposnik, Gustavo; Biessels, Geert Jan; Doubal, Fergus N; Fornage, Myriam; Gorelick, Philip B; Greenberg, Steven M; Higashida, Randall T; Kasner, Scott E; Seshadri, Sudha

2017-02-01

Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians. © 2016 American Heart Association, Inc.

Baseline characteristics, analysis plan and report on feasibility for the Prevention Of Decline in Cognition After Stroke Trial (PODCAST).

PubMed

Scutt, Polly; Blackburn, Dan; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Ford, Gary A; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M; Bath, Philip M

2015-11-07

A common complication after stroke is development of cognitive impairment and dementia. However, effective strategies for reducing the risk of developing these problems remain undefined. Potential strategies include intensive lowering of blood pressure (BP) and/or lipids. This paper summarises the baseline characteristics, statistical analysis plan and feasibility of a randomised control trial of blood pressure and lipid lowering in patients post-stroke with the primary objective of reducing cognitive impairment and dementia. The Prevention Of Decline in Cognition After Stroke Trial (PODCAST) was a multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial internal pilot trial running in secondary and primary care. Participants without dementia were enrolled 3-7 months post ischaemic stroke or spontaneous intracerebral haemorrhage, and randomised to intensive versus guideline BP lowering (target systolic BP <125 mmHg versus <140 mmHg); patients with ischaemic stroke were also randomised to intensive or guideline lipid lowering (target LDL cholesterol <1.4 mmol/L versus <3 mmol/L). The primary outcome was the Addenbrooke's Cognitive Examination-Revised; a key secondary outcome was to assess feasibility of performing a large trial of one or both interventions. Data are number (%) or mean (standard deviation). The trial was planned to last for 8 years with follow-up between 1 and 8 years. The plan for reporting the main results is included as Additional file 2. 83 patients (of a planned 600) were recruited from 19 UK sites between 7 October 2010 and 31 January 2014. Delays, due to difficulties in the provision of excess treatment costs and to complexity of follow-up, led to few centres taking part and a much lower recruitment rate than planned. Patient characteristics at baseline were: age 74 (SD 7) years, male 64 (77 %), index stroke ischaemic 77 (93 %), stroke onset to randomisation 4.5 [SD 1.3] months, Addenbrooke's Cognitive Examination-Revised 86 (of 100, SD 8), Montreal Cognitive Assessment 24 (of 30, SD 3), BP 147/82 (SD 19/11) mmHg, total cholesterol 4.0 (SD 0.8) mmol/L and LDL cholesterol 2.0 (SD 0.7) mmol/L, modified Rankin Scale 1.1 (SD 0.8). Limited recruitment suggests that a large trial is not feasible using the current protocol. The effects of the interventions on BP, lipids, and cognition will be reported in the main publication. ISRCTN85562386 registered on 23 September 2009.

Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial.

PubMed

Benavente, O R; Coffey, C S; Conwit, R; Hart, R G; McClure, L A; Pearce, L A; Pergola, P E; Szychowski, J M

2013-08-10

Lowering of blood pressure prevents stroke but optimum target levels to prevent recurrent stroke are unknown. We investigated the effects of different blood-pressure targets on the rate of recurrent stroke in patients with recent lacunar stroke. In this randomised open-label trial, eligible patients lived in North America, Latin America, and Spain and had recent, MRI-defined symptomatic lacunar infarctions. Patients were recruited between March, 2003, and April, 2011, and randomly assigned, according to a two-by-two multifactorial design, to a systolic-blood-pressure target of 130-149 mm Hg or less than 130 mm Hg. The primary endpoint was reduction in all stroke (including ischaemic strokes and intracranial haemorrhages). Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00059306. 3020 enrolled patients, 1519 in the higher-target group and 1501 in the lower-target group, were followed up for a mean of 3·7 (SD 2·0) years. Mean age was 63 (SD 11) years. After 1 year, mean systolic blood pressure was 138 mm Hg (95% CI 137-139) in the higher-target group and 127 mm Hg (95% CI 126-128) in the lower-target group. Non-significant rate reductions were seen for all stroke (hazard ratio 0·81, 95% CI 0·64-1·03, p=0·08), disabling or fatal stroke (0·81, 0·53-1·23, p=0·32), and the composite outcome of myocardial infarction or vascular death (0·84, 0·68-1·04, p=0·32) with the lower target. The rate of intracerebral haemorrhage was reduced significantly (0·37, 0·15-0·95, p=0·03). Treatment-related serious adverse events were infrequent. Although the reduction in stroke was not significant, our results support that in patients with recent lacunar stroke, the use of a systolic-blood-pressure target of less than 130 mm Hg is likely to be beneficial. National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS). Copyright © 2013 Elsevier Ltd. All rights reserved.

Detailed analysis of periprocedural strokes in patients undergoing intracranial stenting in Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS).

PubMed

Fiorella, David; Derdeyn, Colin P; Lynn, Michael J; Barnwell, Stanley L; Hoh, Brian L; Levy, Elad I; Harrigan, Mark R; Klucznik, Richard P; McDougall, Cameron G; Pride, G Lee; Zaidat, Osama O; Lutsep, Helmi L; Waters, Michael F; Hourihane, J Maurice; Alexandrov, Andrei V; Chiu, David; Clark, Joni M; Johnson, Mark D; Torbey, Michel T; Rumboldt, Zoran; Cloft, Harry J; Turan, Tanya N; Lane, Bethany F; Janis, L Scott; Chimowitz, Marc I

2012-10-01

Enrollment in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial was halted due to the high risk of stroke or death within 30 days of enrollment in the percutaneous transluminal angioplasty and stenting arm relative to the medical arm. This analysis focuses on the patient and procedural factors that may have been associated with periprocedural cerebrovascular events in the trial. Bivariate and multivariate analyses were performed to evaluate whether patient and procedural variables were associated with cerebral ischemic or hemorrhagic events occurring within 30 days of enrollment (termed periprocedural) in the percutaneous transluminal angioplasty and stenting arm. Of 224 patients randomized to percutaneous transluminal angioplasty and stenting, 213 underwent angioplasty alone (n=5) or with stenting (n=208). Of these, 13 had hemorrhagic strokes (7 parenchymal, 6 subarachnoid), 19 had ischemic stroke, and 2 had cerebral infarcts with temporary signs within the periprocedural period. Ischemic events were categorized as perforator occlusions (13), embolic (4), mixed perforator and embolic (2), and delayed stent occlusion (2). Multivariate analyses showed that higher percent stenosis, lower modified Rankin score, and clopidogrel load associated with an activated clotting time above the target range were associated (P ≤ 0.05) with hemorrhagic stroke. Nonsmoking, basilar artery stenosis, diabetes, and older age were associated (P ≤ 0.05) with ischemic events. Periprocedural strokes in SAMMPRIS had multiple causes with the most common being perforator occlusion. Although risk factors for periprocedural strokes could be identified, excluding patients with these features from undergoing percutaneous transluminal angioplasty and stenting to lower the procedural risk would limit percutaneous transluminal angioplasty and stenting to a small subset of patients. Moreover, given the small number of events, the present data should be used for hypothesis generation rather than to guide patient selection in clinical practice. Clinical Trial Registration Information- URL: http://clinicaltrials.gov. Unique Identifier: NCT00576693.

Quality of life assessment in the randomized PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial of patients at risk for stroke with nonvalvular atrial fibrillation.

PubMed

Alli, Oluseun; Doshi, Shepal; Kar, Saibal; Reddy, Vivek; Sievert, Horst; Mullin, Chris; Swarup, Vijay; Whisenant, Brian; Holmes, David

2013-04-30

This study sought to assess quality of life parameters in a subset of patients enrolled in the PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial. The PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) and CHADS2 (congestive heart failure, hypertension, age, diabetes mellitus, and prior stroke, transient ischemic attack, or thromboembolism) score ≥1, a left atrial appendage closure device is noninferior to long-term warfarin for stroke prevention. Given this equivalency, quality of life (QOL) indicators are an important metric for evaluating these 2 different strategies. QOL using the Short-Form 12 Health Survey, version 2, measurement tool was obtained at baseline and 12 months in a subset of 547 patients in the PROTECT AF trial (361 device and 186 warfarin patients). The analysis cohort consisted of patients for whom either paired quality of life data were available after 12 months of follow-up or for patients who died. With the device, the total physical score improved in 34.9% and was unchanged in 29.9% versus warfarin in whom 24.7% were improved and 31.7% were unchanged (p = 0.01). Mental health improvement occurred in 33.0% of the device group versus 22.6% in the warfarin group (p = 0.06). There was a significant improvement in QOL in patients randomized to device for total physical score, physical function, and in physical role limitation compared to control. There were significant differences in the change in total physical score among warfarin naive and not-warfarin naive subgroups in the device group compared to control, but larger gains were seen with the warfarin naive subgroup with a 12-month change of 1.3 ± 8.8 versus -3.6 ± 6.7 (p = 0.0004) device compared to warfarin. Patients with nonvalvular AF at risk for stroke treated with left atrial appendage closure have favorable QOL changes at 12 months versus patients treated with warfarin. (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation [WATCHMAN PROTECT]; NCT00129545). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial.

PubMed

Holmes, David R; Kar, Saibal; Price, Matthew J; Whisenant, Brian; Sievert, Horst; Doshi, Shephal K; Huber, Kenneth; Reddy, Vivek Y

2014-07-08

In the PROTECT AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) trial that evaluated patients with nonvalvular atrial fibrillation (NVAF), left atrial appendage (LAA) occlusion was noninferior to warfarin for stroke prevention, but a periprocedural safety hazard was identified. The goal of this study was to assess the safety and efficacy of LAA occlusion for stroke prevention in patients with NVAF compared with long-term warfarin therapy. This randomized trial further assessed the efficacy and safety of the Watchman device. Patients with NVAF who had a CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and previous stroke/transient ischemic attack) score ≥2 or 1 and another risk factor were eligible. Patients were randomly assigned (in a 2:1 ratio) to undergo LAA occlusion and subsequent discontinuation of warfarin (intervention group, n = 269) or receive chronic warfarin therapy (control group, n = 138). Two efficacy and 1 safety coprimary endpoints were assessed. At 18 months, the rate of the first coprimary efficacy endpoint (composite of stroke, systemic embolism [SE], and cardiovascular/unexplained death) was 0.064 in the device group versus 0.063 in the control group (rate ratio 1.07 [95% credible interval (CrI): 0.57 to 1.89]) and did not achieve the prespecified criteria noninferiority (upper boundary of 95% CrI ≥1.75). The rate for the second coprimary efficacy endpoint (stroke or SE >7 days' postrandomization) was 0.0253 versus 0.0200 (risk difference 0.0053 [95% CrI: -0.0190 to 0.0273]), achieving noninferiority. Early safety events occurred in 2.2% of the Watchman arm, significantly lower than in PROTECT AF, satisfying the pre-specified safety performance goal. Using a broader, more inclusive definition of adverse effects, these still were lower in PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial than in PROTECT AF (4.2% vs. 8.7%; p = 0.004). Pericardial effusions requiring surgical repair decreased from 1.6% to 0.4% (p = 0.027), and those requiring pericardiocentesis decreased from 2.9% to 1.5% (p = 0.36), although the number of events was small. In this trial, LAA occlusion was noninferior to warfarin for ischemic stroke prevention or SE >7 days' post-procedure. Although noninferiority was not achieved for overall efficacy, event rates were low and numerically comparable in both arms. Procedural safety has significantly improved. This trial provides additional data that LAA occlusion is a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF who do not have an absolute contraindication to short-term warfarin therapy. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Does Perturbation Training Prevent Falls after Discharge from Stroke Rehabilitation? A Prospective Cohort Study with Historical Control.

PubMed

Mansfield, Avril; Schinkel-Ivy, Alison; Danells, Cynthia J; Aqui, Anthony; Aryan, Raabeae; Biasin, Louis; DePaul, Vincent G; Inness, Elizabeth L

2017-10-01

Individuals with stroke fall frequently, and no exercise intervention has been shown to prevent falls post stroke. Perturbation-based balance training (PBT), which involves practicing reactions to instability, shows promise for preventing falls in older adults and individuals with Parkinson's disease. This study aimed to determine if PBT during inpatient stroke rehabilitation can prevent falls after discharge into the community. Individuals with subacute stroke completed PBT as part of routine inpatient rehabilitation (n = 31). Participants reported falls experienced in daily life for up to 6 months post discharge. Fall rates were compared to a matched historical control group (HIS) who did not complete PBT during inpatient rehabilitation. Five of 31 PBT participants, compared to 15 of 31 HIS participants, reported at least 1 fall. PBT participants reported 10 falls (.84 falls per person per year) whereas HIS participants reported 31 falls (2.0 falls per person per year). When controlled for follow-up duration and motor impairment, fall rates were lower in the PBT group than the HIS group (rate ratio: .36 [.15, .79]; P = .016). These findings suggest that PBT is promising for reducing falls post stroke. While this was not a randomized controlled trial, this study may provide sufficient evidence for implementing PBT in stroke rehabilitation practice. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Transcatheter patent foramen ovale closure versus medical therapy for cryptogenic stroke: a meta-analysis of randomized clinical trials.

PubMed

Riaz, Irbaz Bin; Dhoble, Abhijeet; Mizyed, Ahmad; Hsu, Chiu-Hsieh; Husnain, Muhammad; Lee, Justin Z; Lotun, Kapildeo; Lee, Kwan S

2013-12-11

There is an association between cryptogenic stroke and patent foramen ovale (PFO). The optimal treatment strategy for secondary prevention remains unclear. The purpose of this study was to analyze aggregate data examining the safety and efficacy of transcatheter device closure versus standard medical therapy in patients with PFO and cryptogenic stroke. A search of published data identified 3 randomized clinical trials for inclusion. The primary outcome was a composite end-point of death, stroke and transient-ischemic attack (TIA). Pre-defined subgroup analysis was performed with respect to baseline characteristics including age, sex, atrial septal aneurysm and shunt size. Data was synthesized using a random effects model and results presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A cohort of 2,303 patients with a history of cryptogenic stroke and PFO were randomized to device closure (n = 1150) and medical therapy (n = 1153). Mean follow-up was 2.5 years. Transcatheter closure was not superior to medical therapy in the secondary prevention of stroke or TIA in intention-to-treat analysis (HR: 0.66, 95% CI: 0.43 to 1.01; p = 0.056). However, the results were statistically significant using per-protocol analysis (HR: 0.64, 95% CI: 0.41 to 0.98; p = 0.043). Males had significant benefit with device closure (HR: 0.48, 95% CI: 0.24 to 0.96; p = 0.038). In this meta-analysis, using intention-to-treat analysis, transcatheter device closure of PFO was not superior to standard medical therapy in the secondary prevention of cryptogenic stroke. Transcatheter closure was superior using per-protocol analysis.

Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.

PubMed

Hart, Robert G; Sharma, Mukul; Mundl, Hardi; Kasner, Scott E; Bangdiwala, Shrikant I; Berkowitz, Scott D; Swaminathan, Balakumar; Lavados, Pablo; Wang, Yongjun; Wang, Yilong; Davalos, Antonio; Shamalov, Nikolay; Mikulik, Robert; Cunha, Luis; Lindgren, Arne; Arauz, Antonio; Lang, Wilfried; Czlonkowska, Anna; Eckstein, Jens; Gagliardi, Rubens J; Amarenco, Pierre; Ameriso, Sebastian F; Tatlisumak, Turgut; Veltkamp, Roland; Hankey, Graeme J; Toni, Danilo; Bereczki, Daniel; Uchiyama, Shinichiro; Ntaios, George; Yoon, Byung-Woo; Brouns, Raf; Endres, Matthias; Muir, Keith W; Bornstein, Natan; Ozturk, Serefnur; O'Donnell, Martin J; De Vries Basson, Matthys M; Pare, Guillaume; Pater, Calin; Kirsch, Bodo; Sheridan, Patrick; Peters, Gary; Weitz, Jeffrey I; Peacock, W Frank; Shoamanesh, Ashkan; Benavente, Oscar R; Joyner, Campbell; Themeles, Ellison; Connolly, Stuart J

2018-06-07

Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .).

Microbleeds in the Secondary Prevention of Small Subcortical Strokes Trial: Stroke, mortality, and treatment interactions.

PubMed

Shoamanesh, Ashkan; Pearce, Lesly A; Bazan, Carlos; Catanese, Luciana; McClure, Leslie A; Sharma, Mukul; Marti-Fabregas, Joan; Anderson, David C; Kase, Carlos S; Hart, Robert G; Benavente, Oscar R

2017-08-01

To characterize cerebral microbleeds (CMBs) in lacunar stroke patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and to assess their relationship with recurrent stroke and death, and response to assigned treatment. SPS3 is a randomized, clinical trial conducted between 2003 and 2011. Patients with recent magnetic resonance imaging (MRI)-documented lacunar infarcts were randomly assigned in a factorial design to target levels of systolic blood pressure (130-149mmHg vs <130mmHg; open label) and to antiplatelet treatment (aspirin/clopidogrel vs aspirin/placebo; double-blinded). The current analysis involves 1,278 trial participants who had a baseline axial T2*-weighted gradient echo MRI sequence allowing for CMB detection. CMBs were present in 30% of 1,278 patients (mean age = 63 years). Male gender (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.3-2.3), history of hypertension (OR = 1.6, 95% CI = 1.2-2.3), increased systolic blood pressure (1.2 per 20mmHg, 95% CI = 1.1-1.4), nondiabetic status (OR = 1.4, 95% CI = 1.1-1.9), multiple old lacunar infarcts (OR = 1.9, 95% CI = 1.5-2.5), and moderate (OR = 1.7, 95% CI = 1.2-2.3) or severe (OR = 4.2, 95% CI = 3.0-5.9) white matter hyperintensities on MRI were independently associated with CMBs. During a mean follow-up of 3.3 years, overall stroke recurrence was 2.5% per patient-year. Patients with CMBs had an adjusted 2-fold increased risk of recurrent stroke (hazard ratio = 2.1, 95% CI = 1.4-3.1). CMBs were not a risk factor for death. There were no statistically significant interactions between CMBs and treatment assignments. Patients with lacunar stroke and CMBs likely harbor a more advanced form of cerebral small vessel disease in need of efficacious therapeutic strategies. Ann Neurol 2017;82:196-207. © 2017 American Neurological Association.

Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study

PubMed Central

Diener, Hans-Christoph; Sacco, Ralph L; Yusuf, Salim; Cotton, Daniel; Ôunpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; Keyser, Jacques De; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2009-01-01

Summary Background The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. Methods Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NTC00153062. Findings 20 332 patients (mean age 66 years) were randomised and followed-up for a median of 2·4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0·38), or with telmisartan versus placebo (p=0·61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups. Interpretation Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan. Funding Boehringer Ingelheim; Bayer-Schering Pharma (in selected countries); GlaxoSmithKline (in selected countries). PMID:18757238

Tailored approaches to stroke health education (TASHE): study protocol for a randomized controlled trial.

PubMed

Ravenell, Joseph; Leighton-Herrmann, Ellyn; Abel-Bey, Amparo; DeSorbo, Alexandra; Teresi, Jeanne; Valdez, Lenfis; Gordillo, Madeleine; Gerin, William; Hecht, Michael; Ramirez, Mildred; Noble, James; Cohn, Elizabeth; Jean-Louis, Giardin; Spruill, Tanya; Waddy, Salina; Ogedegbe, Gbenga; Williams, Olajide

2015-04-19

Stroke is a leading cause of adult disability and mortality. Intravenous thrombolysis can minimize disability when patients present to the emergency department for treatment within the 3 - 4½ h of symptom onset. Blacks and Hispanics are more likely to die and suffer disability from stroke than whites, due in part to delayed hospital arrival and ineligibility for intravenous thrombolysis for acute stroke. Low stroke literacy (poor knowledge of stroke symptoms and when to call 911) among Blacks and Hispanics compared to whites may contribute to disparities in acute stroke treatment and outcomes. Improving stroke literacy may be a critical step along the pathway to reducing stroke disparities. The aim of the current study is to test a novel intervention to increase stroke literacy in minority populations in New York City. In a two-arm cluster randomized trial, we will evaluate the effectiveness of two culturally tailored stroke education films - one in English and one in Spanish - on changing behavioral intent to call 911 for suspected stroke, compared to usual care. These films will target knowledge of stroke symptoms, the range of severity of symptoms and the therapeutic benefit of calling 911, as well as address barriers to timely presentation to the hospital. Given the success of previous church-based programs targeting behavior change in minority populations, this trial will be conducted with 250 congregants across 14 churches (125 intervention; 125 control). Our proposed outcomes are (1) recognition of stroke symptoms and (2) behavioral intent to call 911 for suspected stroke, measured using the Stroke Action Test at the 6-month and 1-year follow-up. This is the first randomized trial of a church-placed narrative intervention to improve stroke outcomes in urban Black and Hispanic populations. A film intervention has the potential to make a significant public health impact, as film is a highly scalable and disseminable medium. Since there is at least one church in almost every neighborhood in the USA, churches have the ability and reach to play an important role in the dissemination and translation of stroke prevention programs in minority communities. NCT01909271 ; July 22, 2013.

Aspirin for primary prevention of cardiovascular events: meta-analysis of randomized controlled trials and subgroup analysis by sex and diabetes status.

PubMed

Xie, Manling; Shan, Zhilei; Zhang, Yan; Chen, Sijing; Yang, Wei; Bao, Wei; Rong, Ying; Yu, Xuefeng; Hu, Frank B; Liu, Liegang

2014-01-01

To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status. We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12. Fourteen trials (107,686 participants) were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85-0.95), myocardial infarction (0.86; 0.75-0.93), ischemic stroke (0.86; 0.75-0.98) and all-cause mortality (0.94; 0.89-0.99). There were also increases in hemorrhagic stroke (1.34; 1.01-1.79) and major bleeding (1.55; 1.35-1.78) with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59-0.85) and ischemic stroke among women (0.77; 0.63-0.93). Aspirin use was associated with a reduction (0.65; 0.51-0.82) in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day) were as large as those obtained with higher doses (650 mg/day). The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials.

Aspirin for Primary Prevention of Cardiovascular Events: Meta-Analysis of Randomized Controlled Trials and Subgroup Analysis by Sex and Diabetes Status

PubMed Central

Zhang, Yan; Chen, Sijing; Yang, Wei; Bao, Wei; Rong, Ying; Yu, Xuefeng; Hu, Frank B.; Liu, Liegang

2014-01-01

Objective To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status. Methods We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12. Results Fourteen trials (107,686 participants) were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85–0.95), myocardial infarction (0.86; 0.75–0.93), ischemic stroke (0.86; 0.75–0.98) and all-cause mortality (0.94; 0.89–0.99). There were also increases in hemorrhagic stroke (1.34; 1.01–1.79) and major bleeding (1.55; 1.35–1.78) with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59–0.85) and ischemic stroke among women (0.77; 0.63–0.93). Aspirin use was associated with a reduction (0.65; 0.51–0.82) in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day) were as large as those obtained with higher doses (650 mg/day). Conclusions The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials. PMID:25360605

Vertebrobasilar ectasia in patients with lacunar stroke: the secondary prevention of small subcortical strokes trial.

PubMed

Nakajima, Makoto; Pearce, Lesly A; Ohara, Nobuyuki; Field, Thalia S; Bazan, Carlos; Anderson, David C; Hart, Robert G; Benavente, Oscar R

2015-05-01

The clinical implications of vertebrobasilar ectasia (VBE) in patients with cerebral small-artery disease are not well defined. We investigated whether VBE is associated with recurrent stroke, major hemorrhage, and death in a large cohort of patients with recent lacunar stroke. Maximum diameters of the vertebral and basilar arteries were measured by magnetic resonance angiography and computed tomographic angiography in 2621 participants in the Secondary Prevention of Small Subcortical Strokes trial. VBE was defined a priori as basilar artery greater than 4.5 mm and/or vertebral artery greater than 4.0 mm. Patient characteristics and risks of stroke recurrence and mortality during follow-up (median, 3.5 years) were compared between patients with and without VBE. VBE affecting 1 or more arteries was present in 200 (7.6%) patients. Patient features independently associated with VBE were increasing age, male sex, white race ethnicity, hypertension, and higher baseline diastolic blood pressure. Baseline systolic blood pressure was inversely associated with VBE. After adjustment for other risk factors, VBE was not predictive of recurrent stroke (hazard ratio [HR], 1.3; 95% confidence interval [CI], .85-1.9) or major hemorrhage (HR, 1.5; CI, .94-2.6), but was of death (HR, 1.7; CI, 1.1-2.7). In this large well-characterized cohort of patients with recent lacunar stroke, VBE was predictive of death but not of recurrent stroke or major hemorrhage. In these exploratory analyses, the frequency of VBE was directly related to diastolic blood pressure but inversely related to systolic blood pressure. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Non-pharmacological interventions for the prevention of venous thromboembolism: a literature review.

PubMed

Hanison, Esther; Corbett, Kevin

2016-10-19

To assess the relative clinical efficacy of different forms of non-pharmacological prophylaxis, intermittent pneumatic compression and graduated compression stockings in reducing the incidence of venous thromboembolism (VTE) in patients hospitalised following acute stroke. This was a thematic synthesis of literature retrieved from a structured bibliographic search of: Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Summon, British Nursing Index, NHS Evidence, Internurse.com, PubMed, Ovid and the websites of other health information resources, such as the Nursing and Midwifery Council, National Institute for Health and Care Excellence and the World Health Organization. Citations were also searched for using: Web of Science, Google Scholar, the Cochrane Central Register of Controlled Trials, Current Controlled Trials, Stroke Trials Registry and Clinical Trials. Intermittent pneumatic compression (IPC) showed a small but statistically significant (P = 0.001) reduction in rates of deep vein thrombosis (DVT), in both symptomatic and asymptomatic DVT, involving proximal or calf veins, with fewer adverse effects such as skin breakdown and ulcers attributed to IPC, as compared to graduated compression stockings. No single intervention was the most effective for VTE prevention. More reliable evidence is required. Clear and extensive guidelines are necessary to ensure high-quality care for patients with acute stroke to improve their quality of life, and reduce morbidity and mortality rates.

Stroke prevention by percutaneous closure of patent foramen ovale: a systematic review and meta-analysis.

PubMed

Wolfrum, Mathias; Froehlich, Georg M; Knapp, Guido; Casaubon, Leanne K; DiNicolantonio, James J; Lansky, Alexandra J; Meier, Pascal

2014-03-01

The role of percutaneous closure of patent foramen oval (PFO) in patients with cryptogenic stroke has been very controversial for years due to a lack of clear evidence. Systematic review and meta-analysis of the effect of percutaneous PFO closure for secondary prevention of cryptogenic strokes as compared to best medical therapy (BMT). Trials were identified through a literature search until 28 May 2013. Controlled clinical trials (randomised and non-randomised) comparing percutaneous PFO closure with BMT. Main end point of interest was stroke. A random effects model was used to calculate the pooled relative risks (RR) with 95% CIs. A total of 14 studies (three randomised controlled trials (RCT) and 11 non-randomised observational studies (non-RCT)), and a total of 4335 patients were included for this analysis. There was no significant treatment effect of PFO closure regarding stroke among the RCT (RR 0.66, 95% CI 0.37 to 1.19, p=0.171). However, among non-RCT stroke was reduced (RR 0.37, 95% CI 0.20 to 0.67, p<0.001) after PFO closure. A time-to-event (stroke) analysis, combining all three RCT and the two non-RCT which applied strict multivariate adjustments, showed a borderline significant risk reduction after PFO closure (HR 0.58, 95% CI 0.33 to 0.99, p=0.047). Neither risk of bleeding nor mortality differed significantly between the groups. However, there was a higher incidence of new onset atrial fibrillation in the closure group (RR 3.50, 95% CI 1.47 to 8.35, p=0.005). Percutaneous closure of PFO in patients with cryptogenic stroke does not appear superior to medical therapy according to currently available randomised data. Furthermore, it is associated with an increased incidence of atrial fibrillation. However, there are signals pointing towards a potential benefit and more research should be strongly encouraged.

Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial.

PubMed

Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Hill, Michael D; Jonasson, Jenny; Kasner, Scott E; Ladenvall, Per; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

2017-04-01

Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial. SOCRATES was a randomised, double-blind, controlled trial of ticagrelor versus aspirin in patients aged 40 years or older with a non-cardioembolic, non-severe acute ischaemic stroke, or high-risk transient ischaemic attack from 674 hospitals in 33 countries. We randomly allocated patients (1:1) to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90, given orally) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90, given orally) within 24 h of symptom onset. Investigators classified all patients into atherosclerotic and non-atherosclerotic groups for the prespecified, exploratory analysis reported in this study. The primary endpoint was the time to occurrence of stroke, myocardial infarction, or death within 90 days. Efficacy analysis was by intention to treat. The SOCRATES trial is registered with ClinicalTrials.gov, number NCT01994720. Between Jan 7, 2014, and Oct 29, 2015, we randomly allocated 13 199 patients (6589 [50%] to ticagrelor and 6610 [50%] to aspirin). Potentially symptomatic ipsilateral atherosclerotic stenosis was reported in 3081 (23%) of 13 199 patients. We found a treatment-by-atherosclerotic stenosis interaction (p=0·017). 103 (6·7%) of 1542 patients with ipsilateral stenosis in the ticagrelor group and 147 (9·6%) of 1539 patients with ipsilateral stenosis in the aspirin group had an occurrence of stroke, myocardial infarction, or death within 90 days (hazard ratio 0·68 [95% CI 0·53-0·88]; p=0·003). In 10 118 patients with no ipsilateral stenosis, 339 (6·7%) of 5047 patients in the ticagrelor group had an occurrence of stroke, myocardial infarction, or death within 90 days compared with 350 (6·9%) of 5071 in the aspirin group (0·97 [0·84-1·13]; p=0·72). There were no significant differences in the proportion of life-threatening bleeding or major or minor bleeding events in patients with ipsilateral stenosis in the ticagrelor group compared with the aspirin group. In this prespecified exploratory analysis, ticagrelor was superior to aspirin at preventing stroke, myocardial infarction, or death at 90 days in patients with acute ischaemic stroke or transient ischaemic attack when associated with ipsilateral atherosclerotic stenosis. An understanding of stroke mechanisms and causes is important to deliver safe and efficacious treatments for early stroke prevention. AstraZeneca. Copyright © 2017 Elsevier Ltd. All rights reserved.

European Primary Care Cardiovascular Society (EPCCS) consensus guidance on stroke prevention in atrial fibrillation (SPAF) in primary care.

PubMed

Hobbs, Fd Richard; Taylor, Clare J; Jan Geersing, Geert; Rutten, Frans H; Brouwer, Judith R

2016-03-01

Atrial fibrillation affects 1-2% of the general population and 10% of those over 75, and is responsible for around a quarter of all strokes. These strokes are largely preventable by the use of anticoagulation therapy, although many eligible patients are not treated. Recent large clinical trials have added to the evidence base on stroke prevention and international clinical guidelines have been updated. Consensus practical recommendations from primary care physicians with an interest in vascular disease and vascular specialists. A focussed all-day meeting, with presentation of summary evidence under each section of this guidance and review of European guidelines on stroke prevention in atrial fibrillation, was used to generate a draft document, which then underwent three cycles of revision and debate before all panel members agreed with the consensus statements. Six areas were identified that included how to identify patients with atrial fibrillation, how to determine their stroke risk and whether to recommend modification of this risk, and what management options are available, with practical recommendations on maximising benefit and minimising risk if anticoagulation is recommended and the reasons why antiplatelet therapy is no longer recommended. The summary evidence is presented for each area and simple summary recommendations are highlighted, with areas of remaining uncertainty listed. Atrial fibrillation-related stroke is a major public health priority for most health systems. This practical guidance can assist generalist community physicians to translate the large evidence base for this cause of preventable stroke and implement this at a local level. © The European Society of Cardiology 2015.

European Primary Care Cardiovascular Society (EPCCS) consensus guidance on stroke prevention in atrial fibrillation (SPAF) in primary care

PubMed Central

Taylor, Clare J; Jan Geersing, Geert; Rutten, Frans H; Brouwer, Judith R

2015-01-01

Background Atrial fibrillation affects 1–2% of the general population and 10% of those over 75, and is responsible for around a quarter of all strokes. These strokes are largely preventable by the use of anticoagulation therapy, although many eligible patients are not treated. Recent large clinical trials have added to the evidence base on stroke prevention and international clinical guidelines have been updated. Design Consensus practical recommendations from primary care physicians with an interest in vascular disease and vascular specialists. Methods A focussed all-day meeting, with presentation of summary evidence under each section of this guidance and review of European guidelines on stroke prevention in atrial fibrillation, was used to generate a draft document, which then underwent three cycles of revision and debate before all panel members agreed with the consensus statements. Results Six areas were identified that included how to identify patients with atrial fibrillation, how to determine their stroke risk and whether to recommend modification of this risk, and what management options are available, with practical recommendations on maximising benefit and minimising risk if anticoagulation is recommended and the reasons why antiplatelet therapy is no longer recommended. The summary evidence is presented for each area and simple summary recommendations are highlighted, with areas of remaining uncertainty listed. Conclusions Atrial fibrillation-related stroke is a major public health priority for most health systems. This practical guidance can assist generalist community physicians to translate the large evidence base for this cause of preventable stroke and implement this at a local level. PMID:25701017

Sex differences in antiplatelet response in ischemic stroke.

PubMed

Meyer, Dawn M; Eastwood, Jo-Ann; Compton, Margaret P; Gylys, Karen; Zivin, Justin A; Ovbiagele, Bruce

2011-07-01

Sex differences exist in the occurrence, treatment and outcome of ischemic stroke. Compared with men, women have more stroke events and are less likely to fully recover from a stroke. Given the rapidly aging population, stroke incidence and mortality among women are projected to substantially rise by 2050. This has important public health consequences. Mitigating the burden of stroke among women will require a fundamental understanding of sex differences and sex-specific issues including cerebrovascular disease pathophysiology, treatment and outcome. An aspect of stroke treatment receiving increasing but insufficient attention involves possible interactions between estrogen levels, antiplatelet drugs and stroke outcome. Emerging evidence suggests that antiplatelet therapy may provide primary stroke protection but not primary myocardial infarction prevention in women, while the opposite may be true among men. Understanding sex-specific issues related to women who experience stroke is critical to clinicians who treat women with antiplatelet medications as part of a secondary stroke prevention regimen; however, the ideal antiplatelet medication, and dose, in women requires further research. In this article we present a conceptual framework for sex differences in antiplatelet treatment response in ischemic stroke, thrombus formation and the mediating role of estrogen, sex differences in antiplatelet treatment response in clinical trials, and sex differences in antiplatelet treatment use in ischemic stroke.

Sex differences in antiplatelet response in ischemic stroke

PubMed Central

Meyer, Dawn M; Eastwood, Jo-Ann; Compton, Margaret P; Gylys, Karen; Zivin, Justin A; Ovbiagele, Bruce

2011-01-01

Sex differences exist in the occurrence, treatment and outcome of ischemic stroke. Compared with men, women have more stroke events and are less likely to fully recover from a stroke. Given the rapidly aging population, stroke incidence and mortality among women are projected to substantially rise by 2050. This has important public health consequences. Mitigating the burden of stroke among women will require a fundamental understanding of sex differences and sex-specific issues including cerebrovascular disease pathophysiology, treatment and outcome. An aspect of stroke treatment receiving increasing but insufficient attention involves possible interactions between estrogen levels, antiplatelet drugs and stroke outcome. Emerging evidence suggests that antiplatelet therapy may provide primary stroke protection but not primary myocardial infarction prevention in women, while the opposite may be true among men. Understanding sex-specific issues related to women who experience stroke is critical to clinicians who treat women with antiplatelet medications as part of a secondary stroke prevention regimen; however, the ideal antiplatelet medication, and dose, in women requires further research. In this article we present a conceptual framework for sex differences in antiplatelet treatment response in ischemic stroke, thrombus formation and the mediating role of estrogen, sex differences in antiplatelet treatment response in clinical trials, and sex differences in antiplatelet treatment use in ischemic stroke. PMID:21790339

Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2

PubMed Central

Diener, Hans-Christoph; Aisenberg, James; Ansell, Jack; Atar, Dan; Breithardt, Günter; Eikelboom, John; Ezekowitz, Michael D.; Granger, Christopher B.; Halperin, Jonathan L.; Hohnloser, Stefan H.; Hylek, Elaine M.; Kirchhof, Paulus; Lane, Deirdre A.; Verheugt, Freek W.A.; Veltkamp, Roland; Lip, Gregory Y.H.

2017-01-01

The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In addition, we discuss the timing of initiation of anticoagulation. In the second of a two-part review, we discuss the use of NOAC for stroke prevention in the following subgroups of patients with AF: (vii) secondary stroke prevention in patients after stroke or transient ischaemic attack (TIA), (viii) patients with acute stroke requiring thrombolysis or thrombectomy, (ix) those initiating or restarting OAC treatment after stroke or TIA, (x) those with renal impairment on dialysis, (xi) the elderly, (xii) those at high risk of gastrointestinal bleeding, and (xiii) those with hypertension. In addition, we discuss adherence and compliance. Finally, we present a summary of treatment suggestions. In specific subgroups of patients with AF, evidence supports the use of particular NOACs and/or particular doses of anticoagulant. The appropriate choice of treatment for these subgroups will help to promote optimal clinical outcomes. PMID:26848150

Analysis of the Cochrane Review: Fibrates for secondary prevention of cardiovascular disease and stroke.

PubMed

Pires da Rosa, Gilberto; Libânio, Diogo; Filipe Azevedo, Luís

2017-01-01

The influence of fibrates on cardiovascular risk has been the focus of several clinical trials. This Cochrane Collaboration Systematic Review evaluated the efficacy of fibrates for secondary prevention of cardiovascular events and stroke, analyzing 13 randomized controlled trials, in a total of 16 112 participants with a history of cardiovascular disease. Fibrates showed a protective effect for the composite outcome of non-fatal stroke, non-fatal myocardial infarction (MI) and vascular death, mainly due to reduction in the risk of non-fatal or fatal MI. Nonetheless, these results largely relied on studies including clofibrate, a drug withdrawn from the market in 2002. No statistically significant differences regarding adverse events were found between fibrates and placebo. Although insufficient to support the routine prescription of fibrates in this setting, this evidence should be taken into account when deciding on lipid-modifying therapy in dyslipidemic patients with a history of cardiovascular disease. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial.

PubMed

Halvorsen, Sigrun; Atar, Dan; Yang, Hongqiu; De Caterina, Raffaele; Erol, Cetin; Garcia, David; Granger, Christopher B; Hanna, Michael; Held, Claes; Husted, Steen; Hylek, Elaine M; Jansky, Petr; Lopes, Renato D; Ruzyllo, Witold; Thomas, Laine; Wallentin, Lars

2014-07-21

The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were ≥75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes. The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial

PubMed Central

Halvorsen, Sigrun; Atar, Dan; Yang, Hongqiu; De Caterina, Raffaele; Erol, Cetin; Garcia, David; Granger, Christopher B.; Hanna, Michael; Held, Claes; Husted, Steen; Hylek, Elaine M.; Jansky, Petr; Lopes, Renato D.; Ruzyllo, Witold; Thomas, Laine; Wallentin, Lars

2014-01-01

Aims The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. Methods and results A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were ≥75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes. Conclusion The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly. PMID:24561548

Blood Pressure Control and Risk of Stroke or Systemic Embolism in Patients With Atrial Fibrillation: Results From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.

PubMed

Rao, Meena P; Halvorsen, Sigrun; Wojdyla, Daniel; Thomas, Laine; Alexander, John H; Hylek, Elaine M; Hanna, Michael; Bahit, M Cecilia; Lopes, Renato D; De Caterina, Raffaele; Erol, Cetin; Goto, Shinya; Lanas, Fernando; Lewis, Basil S; Husted, Steen; Gersh, Bernard J; Wallentin, Lars; Granger, Christopher B

2015-12-01

Patients with atrial fibrillation (AF) and hypertension are at high risk for stroke. Previous studies have shown elevated risk of stroke in patients with AF who have a history of hypertension (regardless of blood pressure [BP] control) and in patients with elevated BP. We assessed the association of hypertension and BP control on clinical outcomes. In ARISTOTLE (n=18 201), BP was evaluated as history of hypertension requiring treatment and elevated BP (systolic ≥140 and/or diastolic ≥90 mm Hg) at study entry and any point during the trial. Hazard ratios (HRs) were derived from Cox proportional hazards models including BP as a time-dependent covariate. A total of 15 916 (87.5%) patients had a history of hypertension requiring treatment. In patients with elevated BP measurement at any point during the trial, the rate of stroke or systemic embolism was significantly higher (HR, 1.53; 95% confidence interval [CI], 1.25-1.86), as was hemorrhagic stroke (HR 1.85; 95% CI, 1.26-2.72) and ischemic stroke (HR, 1.50; 95% CI, 1.18-1.90). Rates of major bleeding were lower in patients with a history of hypertension (HR, 0.80; 95% CI, 0.66-0.98) and nonsignificantly lower in patients with elevated BP at study entry (HR, 0.89; 95% CI, 0.77-1.03). The benefit of apixaban versus warfarin on preventing stroke or systemic embolism was consistent among patients with and without a history of hypertension (P interaction=0.27), BP control at baseline (P interaction=0.43), and BP control during the trial (P interaction=0.97). High BP measurement at any point during the trial was independently associated with a substantially higher risk of stroke or systemic embolism. These results strongly support efforts to treat elevated BP as an important strategy to optimally lower risk of stroke in patients with AF. URL: https://ClinicalTrials.gov/. Unique identifier: NCT00412984. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Cardioembolic Stroke

PubMed Central

Kamel, Hooman; Healey, Jeff S.

2017-01-01

Cardiac embolism accounts for an increasing proportion of ischemic strokes, and might multiply several-fold over the next decades. However, research points to several potential strategies to stem this expected rise in cardioembolic stroke. First, although one-third of strokes are of unclear cause, it is increasingly accepted that many of these cryptogenic strokes arise from a distant embolism rather than in-situ cerebrovascular disease, leading to the recent formulation of “embolic stroke of undetermined source” (ESUS) as a distinct target for investigation. Second, recent clinical trials have indicated that ESUS may often stem from subclinical atrial fibrillation (AF) which can be diagnosed with prolonged heart-rhythm monitoring. Third, emerging evidence indicates that a thrombogenic atrial substrate can lead to atrial thromboembolism even in the absence of AF. Such an atrial cardiopathy may explain many cases of ESUS, and oral anticoagulant drugs may prove to reduce stroke risk from atrial cardiopathy given its parallels to AF. Non-vitamin K antagonist oral anticoagulant (NOAC) drugs have recently expanded therapeutic options for preventing cardioembolic stroke and are currently being tested for stroke prevention in patients with ESUS, including specifically those with atrial cardiopathy. Fourth, increasing appreciation of thrombogenic atrial substrate and the common co-existence of cardiac and extra-cardiac stroke risk factors suggests benefits from global vascular risk factor management in addition to anticoagulation. Finally, improved imaging of ventricular thrombus plus the availability of NOAC drugs may lead to better prevention of stroke from acute myocardial infarction and heart failure. PMID:28154101

Aspirin for Stroke Prevention in Elderly Patients With Vascular Risk Factors: Japanese Primary Prevention Project.

PubMed

Uchiyama, Shinichiro; Ishizuka, Naoki; Shimada, Kazuyuki; Teramoto, Tamio; Yamazaki, Tsutomu; Oikawa, Shinichi; Sugawara, Masahiro; Ando, Katsuyuki; Murata, Mitsuru; Yokoyama, Kenji; Minematsu, Kazuo; Matsumoto, Masayasu; Ikeda, Yasuo

2016-06-01

The effect of aspirin in primary prevention of stroke is controversial among clinical trials conducted in Western countries, and no data are available for Asian populations with a high risk of intracranial hemorrhage. The objective of this study was to evaluate the effect of aspirin on the risk of stroke and intracranial hemorrhage in the Japanese Primary Prevention Project (JPPP). A total of 14 464 patients (age, 60-85 years) with hypertension, dyslipidemia, and diabetes mellitus participated and were randomized into 2 treatment groups: 100 mg of aspirin or no aspirin. The median follow-up period was 5.02 years. The cumulative rate of fatal or nonfatal stroke was similar for the aspirin (2.068%; 95% confidence interval [CI], 1.750-2.443) and no aspirin (2.299%; 95% CI, 1.963-2.692) groups at 5 years; the estimated hazard ratio was 0.927 (95% CI, 0.741-1.160; P=0.509). Aspirin nonsignificantly reduced the risk of ischemic stroke or transient ischemic attack (hazard ratio, 0.783; 95% CI, 0.606-1.012; P=0.061) and nonsignificantly increased the risk of intracranial hemorrhage (hazard ratio, 1.463; 95% CI; 0.956-2.237; P=0.078). A Cox regression adjusted by the risk factors for all stroke, which were age >70 years, smoking, and diabetes mellitus, supported the above result. Aspirin did not show any net benefit for the primary prevention of stroke in elderly Japanese patients with risk factors for stroke, whereas age >70 years, smoking, and diabetes mellitus were risk factors for stroke regardless of aspirin treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00225849. © 2016 American Heart Association, Inc.

Effects of a multifactorial falls prevention program for people with stroke returning home after rehabilitation: a randomized controlled trial.

PubMed

Batchelor, Frances A; Hill, Keith D; Mackintosh, Shylie F; Said, Catherine M; Whitehead, Craig H

2012-09-01

To determine whether a multifactorial falls prevention program reduces falls in people with stroke at risk of recurrent falls and whether this program leads to improvements in gait, balance, strength, and fall-related efficacy. A single blind, multicenter, randomized controlled trial with 12-month follow-up. Participants were recruited after discharge from rehabilitation and followed up in the community. Participants (N=156) were people with stroke at risk of recurrent falls being discharged home from rehabilitation. Tailored multifactorial falls prevention program and usual care (n=71) or control (usual care, n=85). Primary outcomes were rate of falls and proportion of fallers. Secondary outcomes included injurious falls, falls risk, participation, activity, leg strength, gait speed, balance, and falls efficacy. There was no significant difference in fall rate (intervention: 1.89 falls/person-year, control: 1.76 falls/person-year, incidence rate ratio=1.10, P=.74) or the proportion of fallers between the groups (risk ratio=.83, 95% confidence interval=.60-1.14). There was no significant difference in injurious fall rate (intervention: .74 injurious falls/person-year, control: .49 injurious falls/person-year, incidence rate ratio=1.57, P=.25), and there were no significant differences between groups on any other secondary outcome. This multifactorial falls prevention program was not effective in reducing falls in people with stroke who are at risk of falls nor was it more effective than usual care in improving gait, balance, and strength in people with stroke. Further research is required to identify effective interventions for this high-risk group. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

STroke imAging pRevention and treatment (START): A longitudinal stroke cohort study: Clinical trials protocol.

PubMed

Carey, Leeanne M; Crewther, Sheila; Salvado, Olivier; Lindén, Thomas; Connelly, Alan; Wilson, William; Howells, David W; Churilov, Leonid; Ma, Henry; Tse, Tamara; Rose, Stephen; Palmer, Susan; Bougeat, Pierrick; Campbell, Bruce C V; Christensen, Soren; Macaulay, S Lance; Favaloro, Jenny; O' Collins, Victoria; McBride, Simon; Bates, Susan; Cowley, Elise; Dewey, Helen; Wijeratne, Tissa; Gerraty, Richard; Phan, Thanh G; Yan, Bernard; Parsons, Mark W; Bladin, Chris; Barber, P Alan; Read, Stephen; Wong, Andrew; Lee, Andrew; Kleinig, Tim; Hankey, Graeme J; Blacker, David; Markus, Romesh; Leyden, James; Krause, Martin; Grimley, Rohan; Mahant, Neil; Jannes, Jim; Sturm, Jonathan; Davis, Stephen M; Donnan, Geoffrey A

2015-06-01

Stroke and poststroke depression are common and have a profound and ongoing impact on an individual's quality of life. However, reliable biological correlates of poststroke depression and functional outcome have not been well established in humans. Our aim is to identify biological factors, molecular and imaging, associated with poststroke depression and recovery that may be used to guide more targeted interventions. In a longitudinal cohort study of 200 stroke survivors, the START-STroke imAging pRevention and Treatment cohort, we will examine the relationship between gene expression, regulator proteins, depression, and functional outcome. Stroke survivors will be investigated at baseline, 24 h, three-days, three-months, and 12 months poststroke for blood-based biological associates and at days 3-7, three-months, and 12 months for depression and functional outcomes. A sub-group (n = 100), the PrePARE: Prediction and Prevention to Achieve optimal Recovery Endpoints after stroke cohort, will also be investigated for functional and structural changes in putative depression-related brain networks and for additional cognition and activity participation outcomes. Stroke severity, diet, and lifestyle factors that may influence depression will be monitored. The impact of depression on stroke outcomes and participation in previous life activities will be quantified. Clinical significance lies in the identification of biological factors associated with functional outcome to guide prevention and inform personalized and targeted treatments. Evidence of associations between depression, gene expression and regulator proteins, functional and structural brain changes, lifestyle and functional outcome will provide new insights for mechanism-based models of poststroke depression. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Interventions for improving modifiable risk factor control in the secondary prevention of stroke.

PubMed

Lager, Kate E; Mistri, Amit K; Khunti, Kamlesh; Haunton, Victoria J; Sett, Aung K; Wilson, Andrew D

2014-05-02

People with stroke or transient ischaemic attack (TIA) are at increased risk of future stroke and other cardiovascular events. Evidence-based strategies for secondary stroke prevention have been established. However, the implementation of prevention strategies could be improved. To assess the effects of stroke service interventions for implementing secondary stroke prevention strategies on modifiable risk factor control, including patient adherence to prescribed medications, and the occurrence of secondary cardiovascular events. We searched the Cochrane Stroke Group Trials Register (April 2013), the Cochrane Effective Practice and Organisation of Care Group Trials Register (April 2013), CENTRAL (The Cochrane Library 2013, issue 3), MEDLINE (1950 to April 2013), EMBASE (1981 to April 2013) and 10 additional databases. We located further studies by searching reference lists of articles and contacting authors of included studies. We included randomised controlled trials (RCTs) that evaluated the effects of organisational or educational and behavioural interventions (compared with usual care) on modifiable risk factor control for secondary stroke prevention. Two review authors selected studies for inclusion and independently extracted data. One review author assessed the risk of bias for the included studies. We sought missing data from trialists. This review included 26 studies involving 8021 participants. Overall the studies were of reasonable quality, but one study was considered at high risk of bias. Fifteen studies evaluated predominantly organisational interventions and 11 studies evaluated educational and behavioural interventions for patients. Results were pooled where appropriate, although some clinical and methodological heterogeneity was present. The estimated effects of organisational interventions were compatible with improvements and no differences in the modifiable risk factors mean systolic blood pressure (mean difference (MD) -2.57 mmHg; 95% confidence interval (CI) -5.46 to 0.31), mean diastolic blood pressure (MD -0.90 mmHg; 95% CI -2.49 to 0.68), blood pressure target achievement (OR 1.24; 95% CI 0.94 to 1.64) and mean body mass index (MD -0.68 kg/m(2); 95% CI -1.46 to 0.11). There were no significant effects of organisational interventions on lipid profile, HbA1c, medication adherence or recurrent cardiovascular events. Educational and behavioural interventions were not generally associated with clear differences in any of the review outcomes, with only two exceptions. Pooled results indicated that educational interventions were not associated with clear differences in any of the review outcomes. The estimated effects of organisational interventions were compatible with improvements and no differences in several modifiable risk factors. We identified a large number of ongoing studies, suggesting that research in this area is increasing. The use of standardised outcome measures would facilitate the synthesis of future research findings.

Predictors of mortality in patients with lacunar stroke in the secondary prevention of small subcortical strokes trial.

PubMed

Sharma, Mukul; Pearce, Lesly A; Benavente, Oscar R; Anderson, David C; Connolly, Stuart J; Palacio, Santiago; Coffey, Christopher S; Hart, Robert G

2014-10-01

The Secondary Prevention of Small Subcortical Stroke trial (SPS3) recruited participants meeting clinical and radiological criteria for symptomatic lacunes. Individuals randomized to dual antiplatelet therapy with clopidogrel and aspirin had an unanticipated increase in all-cause mortality compared with those assigned to aspirin. We investigated the factors associated with mortality in this well-characterized population. We identified independent predictors of mortality among baseline demographic and clinical factors by Cox regression analysis in participants of the SPS3 trial. Separately, we examined the effect on mortality of nonfatal bleeding during the trial. During a mean follow-up of 3.6 years, the mortality rate was 1.78% per year for the 3020 participants (mean age, 63 years). Significant independent predictors of mortality at study entry were age, diabetes mellitus, history of hypertension, systolic blood pressure (hazard ratio [HR], 1.3 per 20 mm Hg increase), serum hemoglobin<13 g/dL (HR, 1.6), renal function (HR, 1.3 per estimated glomerular filtration rate decrease of 20 mL/min), and body mass index (HR, 1.8 per 10 kg/m2 decrease). Participants with ischemic heart disease (P=0.01 for interaction) and normotensive/prehypertensive participants (P=0.03 for interaction) were at increased risk if assigned to dual antiplatelet therapy. Nonfatal major hemorrhage increased mortality in both treatment arms (HR, 4.5; 95% confidence interval, 3.1-6.6; P<0.001). Unexpected interactions between assigned antiplatelet therapy and each of ischemic heart disease and normal/prehypertensive status accounted for increased mortality among patients with recent lacunar stroke given dual antiplatelet therapy. Despite extensive exploratory analyses, the mechanisms underlying these interactions are uncertain. http://www.SPS3ClinicalTrials.gov. Unique identifier: NCT00059306. © 2014 American Heart Association, Inc.

Hospitalized Infection as a Trigger for Acute Ischemic Stroke: The Atherosclerosis Risk in Communities Study.

PubMed

Cowan, Logan T; Alonso, Alvaro; Pankow, James S; Folsom, Aaron R; Rosamond, Wayne D; Gottesman, Rebecca F; Lakshminarayan, Kamakshi

2016-06-01

Acute triggers for ischemic stroke, which may include infection, are understudied, as is whether background cardiovascular disease (CVD) risk modifies such triggering. We hypothesized that infection increases acute stroke risk, especially among those with low CVD risk. Hospitalized strokes and infections were identified in the Atherosclerosis Risk in Communities (ARIC) cohort. A case-crossover design and conditional logistic regression were used to compare hospitalized infections among patients with stroke (14, 30, 42, and 90 days before stroke) with corresponding control periods 1 year and 2 years before stroke. Background CVD risk was assessed at both visit 1 and the visit most proximal to stroke, with risk dichotomized at the median. A total of 1008 adjudicated incident ischemic strokes were included. Compared with control periods, hospitalized infection was more common within 2 weeks before stroke (14-day odds ratio [OR], 7.7; 95% CI, 2.1-27.3); the strength of association declined with increasing time in the exposure window before stroke (30-day OR, 5.7 [95% CI, 2.3-14.3]; 42-day OR, 4.5 [95% CI, 2.0-10.2]; and 90-day OR, 3.6 [95% CI, 2.1-6.5]). Stroke risk was higher among those with low compared with high CVD risk, with this interaction reaching statistical significance for some exposure periods. These results support the hypothesis that hospitalized infection is a trigger of ischemic stroke and may explain some cryptogenic strokes. Infection control efforts may prevent strokes. CVD preventive therapies may prevent strokes if used in the peri-infection period, but clinical trials are needed. © 2016 American Heart Association, Inc.

Do open label blinded outcome studies of novel anticoagulants versus warfarin have equivalent validity to those carried out under double-blind conditions?

PubMed

O'Neil, William M; Welner, Sharon A; Lip, Gregory Y H

2013-03-01

Recent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54-1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73-2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.

Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies.

PubMed

Hart, R G; Pearce, L A; Miller, V T; Anderson, D C; Rothrock, J F; Albers, G W; Nasco, E

2000-01-01

While atrial fibrillation (AF) increases the risk of cardioembolic stroke, some ischemic strokes in AF patients are noncardioembolic. To assess ischemic stroke mechanisms in AF and to compare their responses to antithrombotic therapies. On-therapy analyses of ischemic strokes occurring in 3,950 participants in the Stroke Prevention in Atrial Fibrillation I-III clinical trials. Strokes were classified by presumed mechanism according to specified neurologic features by neurologists unaware of antithrombotic therapy. Of 217 ischemic strokes, 52% were classified as probably cardioembolic, 24% as noncardioembolic, and 24% as of uncertain cause (i.e., 68% of classifiable infarcts were deemed cardioembolic). Compared to those receiving placebo or no antithrombotic therapy, the proportion of cardioembolic stroke was lower in patients taking adjusted-dose warfarin (p = 0.02), while the proportion of noncardioembolic stroke was lower in those taking aspirin (p = 0.06). Most (56%) ischemic strokes occurring in AF patients taking adjusted-dose warfarin were noncardioembolic vs. 16% of strokes in those taking aspirin. Adjusted-dose warfarin reduced cardioembolic strokes by 83% (p < 0.001) relative to aspirin. Cardioembolic strokes were particularly disabling (p = 0.05). Most ischemic strokes in AF patients are probably cardioembolic, and these are sharply reduced by adjusted-dose warfarin. Aspirin in AF patients appears to primarily reduce noncardioembolic strokes. AF patients at highest risk for stroke have the highest rates of cardioembolic stroke and have the greatest reduction in stroke by warfarin. Copyright 2000 S. Karger AG, Basel

Efficacy of a Community-Based Physical Activity Program KM2H2 for Stroke and Heart Attack Prevention among Senior Hypertensive Patients: A Cluster Randomized Controlled Phase-II Trial

PubMed Central

Gong, Jie; Chen, Xinguang; Li, Sijian

2015-01-01

Objective To evaluate the efficacy of the program Keep Moving toward Healthy Heart and Healthy Brain (KM2H2) in encouraging physical activities for the prevention of heart attack and stroke among hypertensive patients enrolled in the Community-Based Hypertension Control Program (CBHCP). Design Cluster randomized controlled trial with three waves of longitudinal assessments at baseline, 3 and 6 months post intervention. Setting Community-based and patient-centered self-care for behavioral intervention in urban settings of China. Participants A total of 450 participants diagnosed with hypertension from 12 community health centers in Wuhan, China were recruited, and were randomly assigned by center to receive either KM2H2 plus standard CBHCP care (6 centers and 232 patients) or the standard care only (6 centers and 218 patients). Intervention KM2H2 is a behavioral intervention guided by the Transtheoretical Model, the Model of Personalized Medicine and Social Capital Theory. It consists of six intervention sessions and two booster sessions engineered in a progressive manner. The purpose is to motivate and maintain physical activities for the prevention of heart attack and stroke. Outcome Measures Heart attack and stroke (clinically diagnosed, primary outcome), blood pressure (measured, secondary outcome), and physical activity (self-report, tertiary outcome) were assessed at the individual level during the baseline, 3- and 6-month post-intervention. Results Relative to the standard care, receiving KM2H2 was associated with significant reductions in the incidence of heart attack (3.60% vs. 7.03%, p < .05) and stroke (5.11% vs. 9.90%, p<0.05), and moderate reduction in blood pressure (-3.72mmHg in DBP and -2.92 mmHg in DBP) at 6-month post-intervention; and significant increases in physical activity at 3- (d = 0.53, 95% CI: 0.21, 0.85) and 6-month (d = 0.45, 95% CI: 0.04, 0.85) post-intervention, respectively. Conclusion The program KM2H2 is efficacious to reduce the risk of heart attack and stroke among senior patients who are on anti-hypertensive medication. Findings of this study provide solid data supporting a formal phase-III trial to establish the effectiveness of KM2H2 for use in community settings for prevention. Trial Registration ISRCTN Register ISRCTN12608966 PMID:26426421

Primary stroke prevention and hypertension treatment: which is the first-line strategy?

PubMed

Ravenni, Roberta; Jabre, Joe F; Casiglia, Edoardo; Mazza, Alberto

2011-07-05

Hypertension (HT) is considered the main classic vascular risk factor for stroke and the importance of lowering blood pressure (BP) is well established. However, not all the benefit of antihypertensive treatment is due to BP reduction per se, as the effect of reducing the risk of stroke differs among classes of antihypertensive agents. Extensive evidences support that angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), dihydropyridine calcium channel blockers (CCB) and thiazide diuretics each reduced risk of stroke compared with placebo or no treatment. Therefore, when combination therapy is required, a combination of these antihypertensive classes represents a logical approach. Despite the efficacy of antihypertensive therapy a large proportion of the population, still has undiagnosed or inadequately treated HT, and remain at high risk of stroke. In primary stroke prevention current guidelines recommend a systolic/diastolic BP goal of <140/<90 mmHg in the general population and <130/80 mmHg in diabetics and in subjects with high cardiovascular risk and renal disease. The recent release in the market of the fixed-dose combination (FDC) of ACEI or ARB and CCB should provide a better control of BP. However to confirm the efficacy of the FDC in primary stroke prevention, clinical intervention trials are needed.

Magnetic resonance imaging/angiography and transcranial Doppler velocities in sickle cell anemia: results from the SWiTCH trial

PubMed Central

Helton, Kathleen J.; Adams, Robert J.; Kesler, Karen L.; Lockhart, Alex; Aygun, Banu; Driscoll, Catherine; Heeney, Matthew M.; Jackson, Sherron M.; Krishnamurti, Lakshmanan; Miller, Scott T.; Sarnaik, Sharada A.; Schultz, William H.

2014-01-01

The Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial compared standard (transfusions/chelation) to alternative (hydroxyurea/phlebotomy) treatment to prevent recurrent stroke and manage iron overload in children chronically transfused over 7 years before enrollment. Standardized brain magnetic resonance imaging/magnetic resonance angiography (MRA) and transcranial Doppler (TCD) exams were performed at entry and exit, with a central blinded review. A novel MRA vasculopathy grading scale demonstrated frequent severe baseline left/right vessel stenosis (53%/41% ≥Grade 4); 31% had no vessel stenosis on either side. Baseline parenchymal injury was prevalent (85%/79% subcortical, 53%/37% cortical, 50%/35% subcortical and cortical). Most children had low or uninterpretable baseline middle cerebral artery TCD velocities, which were associated with worse stenoses (incidence risk ratio [IRR] = 5.1, P ≤ .0001 and IRR = 4.1, P < .0001) than normal velocities; only 2% to 12% had any conditional/abnormal velocity. Patients with adjudicated stroke (7) and transient ischemic attacks (19 in 11 standard/8 alternative arm subjects) had substantial parenchymal injury/vessel stenosis. At exit, 1 child (alternative arm) had a new silent infarct, and another had worse stenosis. SWiTCH neuroimaging data document severe parenchymal and vascular abnormalities in children with SCA and stroke and support concerns about chronic transfusions lacking effectiveness for preventing progressive cerebrovascular injury. The novel SWiTCH vasculopathy grading scale warrants validation testing and consideration for use in future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT00122980. PMID:24914136

New perspectives on the pharmacotherapy of ischemic stroke.

PubMed

Bradberry, J Chris; Fagan, Susan C; Gray, David R; Moon, Yong S K

2004-01-01

To provide an overview of the impact of ischemic stroke and the steps that can be taken to reduce its burden through greater awareness of the disease, improved diagnosis and better treatment, with emphasis on the use of antiplatelet agents. Recent (1995-2003) published scientific literature, as identified by the authors through Medline searches, using the terms stroke, transient ischemic attack, cerebrovascular disease, atherothrombosis, risk factors, pharmacotherapy, prevention, and reviews on treatment. Recent systematic English-language review articles and reports of controlled randomized clinical trials were screened for inclusion. Ischemic stroke is generally the result of an atherothrombotic process leading to vessel obstruction or narrowing. Of the two types of ischemic stroke, thrombotic stroke is caused by a thrombus that develops within the cerebral vasculature, while embolic stroke arises from a distant embolus that lodges in a cerebral artery. The neurologic manifestations of stroke depend on the location of injury in the brain and the degree of ischemia or infarction. Symptoms may be reversible or irreversible and range from sensory deficits to hemiplegia. Risk factors for development of ischemic stroke include hypertension, diabetes, dyslipidemia, smoking, atrial fibrillation, prior stroke, and transient ischemic attack. Tissue plasminogen activator is currently the only available drug treatment for acute ischemic stroke. Stroke recurrence rates are high (about 40% over 5 years), and all ischemic stroke patients should receive antithrombotic therapy (unless contraindicated) for secondary prevention. Of the oral antiplatelet therapies, aspirin, clopidogrel (Plavix--Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership), and the extended-release dipyridamole plus aspirin combination are acceptable first-line agents, while anticoagulants (warfarin) are preferred in patients with atrial fibrillation. Lifestyle changes and drug therapy are important components of primary and secondary prevention strategies in ischemic stroke. Risk factors such as elevated blood pressure and high cholesterol should be aggressively treated. Antiplatelet agents, antihypertensive agents, and cholesterol-lowering agents are therapeutic cornerstones for secondary prevention.

Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation).

PubMed

Goodman, Shaun G; Wojdyla, Daniel M; Piccini, Jonathan P; White, Harvey D; Paolini, John F; Nessel, Christopher C; Berkowitz, Scott D; Mahaffey, Kenneth W; Patel, Manesh R; Sherwood, Matthew W; Becker, Richard C; Halperin, Jonathan L; Hacke, Werner; Singer, Daniel E; Hankey, Graeme J; Breithardt, Gunter; Fox, Keith A A; Califf, Robert M

2014-03-11

This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Antithrombotic therapy in patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention: should we change our practice after the PIONEER AF-PCI and RE-DUAL PCI trials?

PubMed

Duerschmied, D; Brachmann, J; Darius, H; Frey, N; Katus, H A; Rottbauer, W; Schäfer, A; Thiele, H; Bode, C; Zeymer, Uwe

2018-04-20

The number of patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is increasing. Since these patients have a CHA 2 DS 2 -VASc score of 1 or higher, they should be treated with oral anticoagulation to prevent stroke. However, combination therapy with oral anticoagulation for prevention of embolic stroke and dual platelet inhibition for prevention of coronary thrombosis significantly increases bleeding complications. The optimal combination, intensity and duration of antithrombotic combination therapy is still not known. In the rather small randomized WOEST trial, the combination of a vitamin K antagonist (VKA) and clopidogrel decreased bleeding compared to the conventional triple therapy with VKA, clopidogrel and aspirin. In the PIONEER AF-PCI trial, two rivaroxaban-based treatment regimens significantly reduced bleeding complications compared to conventional triple therapy without increasing embolic or ischemic complications following PCI. Dual therapy with rivaroxaban and clopidogrel appeared to provide an optimal risk-benefit ratio. In the RE-DUAL PCI trial, dual therapy with dabigatran also reduced bleeding complications compared to conventional triple therapy. With respect to the composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization dabigatran-based dual therapy was non-inferior to VKA-based triple therapy. The upcoming trials AUGUSTUS with apixaban and ENTRUST-PCI with edoxaban will further examine the use of NOACs in this setting. While recent guidelines recommend NOAC-based dual therapy in only a subset of patients (those who are at increased risk of bleeding), the available data now suggest that this should be the preferred choice for the majority of patients. Adding aspirin to this primary choice for up to 4 weeks in patients at especially high ischemic risk would likely prevent atherothrombotic events, but this needs further investigation. Taken together, it is time to adjust our practice and move to dual therapy consisting of a NOAC plus clopidogrel in most patients.

Training Rapid Stepping Responses in an Individual With Stroke

PubMed Central

Inness, Elizabeth L.; Komar, Janice; Biasin, Louis; Brunton, Karen; Lakhani, Bimal; McIlroy, William E.

2011-01-01

Background and Purpose Compensatory stepping reactions are important responses to prevent a fall following a postural perturbation. People with hemiparesis following a stroke show delayed initiation and execution of stepping reactions and often are found to be unable to initiate these steps with the more-affected limb. This case report describes a targeted training program involving repeated postural perturbations to improve control of compensatory stepping in an individual with stroke. Case Description Compensatory stepping reactions of a 68-year-old man were examined 52 days after left hemorrhagic stroke. He required assistance to prevent a fall in all trials administered during his initial examination because he showed weight-bearing asymmetry (with more weight borne on the more-affected right side), was unable to initiate stepping with the right leg (despite blocking of the left leg in some trials), and demonstrated delayed response times. The patient completed 6 perturbation training sessions (30–60 minutes per session) that aimed to improve preperturbation weight-bearing symmetry, to encourage stepping with the right limb, and to reduce step initiation and completion times. Outcomes Improved efficacy of compensatory stepping reactions with training and reduced reliance on assistance to prevent falling were observed. Improvements were noted in preperturbation asymmetry and step timing. Blocking the left foot was effective in encouraging stepping with the more-affected right foot. Discussion This case report demonstrates potential short-term adaptations in compensatory stepping reactions following perturbation training in an individual with stroke. Future work should investigate the links between improved compensatory step characteristics and fall risk in this vulnerable population. PMID:21511992

Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study.

PubMed

Gulløv, A L; Koefoed, B G; Petersen, P; Pedersen, T S; Andersen, E D; Godtfredsen, J; Boysen, G

1998-07-27

Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients. The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study was a randomized, controlled trial examining the following therapies: warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; and aspirin, 300 mg/d. These were compared with adjusted-dose warfarin therapy (international normalized ratio of prothrombin time [INR], 2.0-3.0). Stroke or a systemic thromboembolic event was the primary outcome event. Transient ischemic attack, acute myocardial infarction, and death were secondary events. Data were handled as survival data, and risk factors were identified using the Cox proportional hazards model. The trial was scheduled for 6 years from May 1, 1993, but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study, our trial was prematurely terminated on October 2, 1996. We included 677 patients (median age, 74 years). The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin; 7.2%, warfarin plus aspirin; 3.6%, aspirin; and 2.8%, adjusted-dose warfarin (P = .67). After 3 years, no difference among the groups was seen. Major bleeding events were rare. Although the difference was insignificant, adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.

Antiplatelet regimens in the long-term secondary prevention of transient ischaemic attack and ischaemic stroke: an updated network meta-analysis

PubMed Central

Niu, Peng-Peng; Guo, Zhen-Ni; Jin, Hang; Xing, Ying-Qi; Yang, Yi

2016-01-01

Objective To examine the comparative efficacy and safety of different antiplatelet regimens in patients with prior non-cardioembolic ischaemic stroke or transient ischaemic attack. Design Systematic review and network meta-analysis. Data sources As on 31 March 2015, all randomised controlled trials that investigated the effects of antiplatelet agents in the long-term (≥3 months) secondary prevention of non-cardioembolic transient ischaemic attack or ischaemic stroke were searched and identified. Outcome measures The primary outcome measure of efficacy was serious vascular events (non-fatal stroke, non-fatal myocardial infarction and vascular death). The outcome measure of safety was any bleeding. Results A total of 36 randomised controlled trials (82 144 patients) were included. Network meta-analysis showed that cilostazol was significantly more effective than clopidogrel (OR 0.77, 95% credible interval 0.60–0.98) and low-dose (75–162 mg daily) aspirin (0.69, 0.55–0.86) in the prevention of serious vascular events. Aspirin (50 mg daily) plus dipyridamole (400 mg daily) and clopidogrel reduced the risk of serious vascular events compared with low-dose aspirin; however, the difference was not statistically significant. Furthermore, low-dose aspirin was as effective as higher daily doses. Cilostazol was associated with a significantly lower bleeding risk than most of the other regimens. Moreover, aspirin plus clopidogrel was associated with significantly more haemorrhagic events than other regimens. Direct comparisons showed similar results as the network meta-analysis. Conclusions Cilostazol was significantly more effective than aspirin and clopidogrel alone in the long-term prevention of serious vascular events in patients with prior non-cardioembolic ischaemic stroke or transient ischaemic attack. Cilostazol was associated with a significantly lower bleeding risk than low-dose aspirin (75–162 mg daily) and aspirin (50 mg daily) plus dipyridamole (400 mg daily). Low-dose aspirin was as effective as higher daily doses. However, further large, randomised, controlled, head-to-head trials are needed, especially in non-Asian ethnic groups. PMID:26988347

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.

PubMed

Sterne, Jonathan Ac; Bodalia, Pritesh N; Bryden, Peter A; Davies, Philippa A; López-López, Jose A; Okoli, George N; Thom, Howard Hz; Caldwell, Deborah M; Dias, Sofia; Eaton, Diane; Higgins, Julian Pt; Hollingworth, Will; Salisbury, Chris; Savović, Jelena; Sofat, Reecha; Stephens-Boal, Annya; Welton, Nicky J; Hingorani, Aroon D

2017-03-01

Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements. To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE. Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials. Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention). Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE). NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network. Efficacy  Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Safety  Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness. MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. The stroke prevention in AF review search was run on the 12 March 2014 and updated on 15 September 2014, and covered the period 2010 to September 2014. The search for the three reviews in VTE was run on the 19 March 2014, updated on 15 September 2014, and covered the period 2008 to September 2014. Two reviewers screened search results, extracted and checked data, and assessed risk of bias. For each outcome we conducted standard meta-analysis and NMA. We evaluated cost-effectiveness using discrete-time Markov models. Apixaban (Eliquis ® , Bristol-Myers Squibb, USA; Pfizer, USA) [5 mg bd (twice daily)] was ranked as among the best interventions for stroke prevention in AF, and had the highest expected net benefit. Edoxaban (Lixiana ® , Daiichi Sankyo, Japan) [60 mg od (once daily)] was ranked second for major bleeding and all-cause mortality. Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE. For acute treatment and secondary prevention of VTE, we found little evidence that NOACs offer an efficacy advantage over warfarin, but the risk of bleeding complications was lower for some NOACs than for warfarin. For a willingness-to-pay threshold of > £5000, apixaban (5 mg bd) had the highest expected net benefit for acute treatment of VTE. Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE: our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication. NOACs have advantages over warfarin in patients with AF, but we found no strong evidence that they should replace warfarin or LMWH in primary prevention, treatment or secondary prevention of VTE. These relate mainly to shortfalls in the primary data: in particular, there were no head-to-head comparisons between different NOAC drugs. Calculating the expected value of sample information to clarify whether or not it would be justifiable to fund one or more head-to-head trials. This study is registered as PROSPERO CRD42013005324, CRD42013005331 and CRD42013005330. The National Institute for Health Research Health Technology Assessment programme.

Short-duration hypothermia after ischemic stroke prevents delayed intracranial pressure rise.

PubMed

Murtha, L A; McLeod, D D; McCann, S K; Pepperall, D; Chung, S; Levi, C R; Calford, M B; Spratt, N J

2014-07-01

Intracranial pressure elevation, peaking three to seven post-stroke is well recognized following large strokes. Data following small-moderate stroke are limited. Therapeutic hypothermia improves outcome after cardiac arrest, is strongly neuroprotective in experimental stroke, and is under clinical trial in stroke. Hypothermia lowers elevated intracranial pressure; however, rebound intracranial pressure elevation and neurological deterioration may occur during rewarming. (1) Intracranial pressure increases 24 h after moderate and small strokes. (2) Short-duration hypothermia-rewarming, instituted before intracranial pressure elevation, prevents this 24 h intracranial pressure elevation. Long-Evans rats with two hour middle cerebral artery occlusion or outbred Wistar rats with three hour middle cerebral artery occlusion had intracranial pressure measured at baseline and 24 h. Wistars were randomized to 2·5 h hypothermia (32·5°C) or normothermia, commencing 1 h after stroke. In Long-Evans rats (n = 5), intracranial pressure increased from 10·9 ± 4·6 mmHg at baseline to 32·4 ± 11·4 mmHg at 24 h, infarct volume was 84·3 ± 15·9 mm(3) . In normothermic Wistars (n = 10), intracranial pressure increased from 6·7 ± 2·3 mmHg to 31·6 ± 9·3 mmHg, infarct volume was 31·3 ± 18·4 mm(3) . In hypothermia-treated Wistars (n = 10), 24 h intracranial pressure did not increase (7·0 ± 2·8 mmHg, P < 0·001 vs. normothermia), and infarct volume was smaller (15·4 ± 11·8 mm(3) , P < 0·05). We saw major intracranial pressure elevation 24 h after stroke in two rat strains, even after small strokes. Short-duration hypothermia prevented the intracranial pressure rise, an effect sustained for at least 18 h after rewarming. The findings have potentially important implications for design of future clinical trials. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Methods to improve patient recruitment and retention in stroke trials.

PubMed

Berge, Eivind; Stapf, Christian; Al-Shahi Salman, Rustam; Ford, Gary A; Sandercock, Peter; van der Worp, H Bart; Petersson, Jesper; Dippel, Diederik Wj; Krieger, Derk W; Lees, Kennedy R

2016-08-01

The success of randomized-controlled stroke trials is dependent on the recruitment and retention of a sufficient number of patients, but fewer than half of all trials meet their target number of patients. We performed a search and review of the literature, and conducted a survey and workshop among 56 European stroke trialists, to identify barriers, suggest methods to improve recruitment and retention, and make a priority list of interventions that merit further evaluation. The survey and workshop identified a number of barriers to patient recruitment and retention, from patients' incapacity to consent, to handicaps that prevent patients from participation in trial-specific follow-up. Methods to improve recruitment and retention may include simple interventions with individual participants, funding of research networks, and reimbursement of new treatments by health services only when delivered within clinical trials. The literature review revealed that few methods have been formally evaluated. The top five priorities for evaluation identified in the workshop were as follows: short and illustrated patient information leaflets, nonwritten consent, reimbursement for new interventions only within a study, and monetary incentives to institutions taking part in research (for recruitment); and involvement of patient groups, remote and central follow-up, use of mobile devices, and reminders to patients about their consent to participate (for retention). Many interventions have been used with the aim of improving recruitment and retention of patients in stroke studies, but only a minority has been evaluated. We have identified methods that could be tested, and propose that such evaluations may be nested within on-going clinical trials. © 2016 World Stroke Organization.

Evidence, education and practice.

PubMed

Kaste, Markku

2006-01-01

Stroke causes greater loss of quality-adjusted life years than any other disease and is also one of the most expensive disorders. The burden of stroke will increase in the future due to change in the age structure of populations. We have a vast body of evidence on how to prevent stroke and how to treat stroke patients. Good examples are treatment of hypertension, antithrombotic agents and carotid surgery in stroke prevention, thrombolysis in ischaemic stroke and stroke unit care for all stroke patients. We only have to translate scientific evidence into daily practice. If some pieces are missing, it is our duty to generate them through research. While taking part in randomized clinical trials (RCTs), the discipline, an essential part of RCTs, will improve the daily care of all stroke patients. Besides RCTs there are many other sources of scientific evidence for stroke management, one of which is the European Stroke Initiative (EUSI). The mission of the EUSI is to improve and optimize stroke management in Europe through education and by offering best practice guidelines. Also national and international societies and organizations play an important role in providing education. The human factor is one obstacle to more successful stroke management because to be more effective we must change our own clinical routine. We can make a difference by applying available evidence to our daily practice. Copyright (c) 2006 S. Karger AG, Basel.

Efficacy of a Community-Based Physical Activity Program KM2H2 for Stroke and Heart Attack Prevention among Senior Hypertensive Patients: A Cluster Randomized Controlled Phase-II Trial.

PubMed

Gong, Jie; Chen, Xinguang; Li, Sijian

2015-01-01

To evaluate the efficacy of the program Keep Moving toward Healthy Heart and Healthy Brain (KM2H2) in encouraging physical activities for the prevention of heart attack and stroke among hypertensive patients enrolled in the Community-Based Hypertension Control Program (CBHCP). Cluster randomized controlled trial with three waves of longitudinal assessments at baseline, 3 and 6 months post intervention. Community-based and patient-centered self-care for behavioral intervention in urban settings of China. A total of 450 participants diagnosed with hypertension from 12 community health centers in Wuhan, China were recruited, and were randomly assigned by center to receive either KM2H2 plus standard CBHCP care (6 centers and 232 patients) or the standard care only (6 centers and 218 patients). KM2H2 is a behavioral intervention guided by the Transtheoretical Model, the Model of Personalized Medicine and Social Capital Theory. It consists of six intervention sessions and two booster sessions engineered in a progressive manner. The purpose is to motivate and maintain physical activities for the prevention of heart attack and stroke. Heart attack and stroke (clinically diagnosed, primary outcome), blood pressure (measured, secondary outcome), and physical activity (self-report, tertiary outcome) were assessed at the individual level during the baseline, 3- and 6-month post-intervention. Relative to the standard care, receiving KM2H2 was associated with significant reductions in the incidence of heart attack (3.60% vs. 7.03%, p < .05) and stroke (5.11% vs. 9.90%, p<0.05), and moderate reduction in blood pressure (-3.72 mmHg in DBP and -2.92 mmHg in DBP) at 6-month post-intervention; and significant increases in physical activity at 3- (d = 0.53, 95% CI: 0.21, 0.85) and 6-month (d = 0.45, 95% CI: 0.04, 0.85) post-intervention, respectively. The program KM2H2 is efficacious to reduce the risk of heart attack and stroke among senior patients who are on anti-hypertensive medication. Findings of this study provide solid data supporting a formal phase-III trial to establish the effectiveness of KM2H2 for use in community settings for prevention. ISRCTN Register ISRCTN12608966.

What is Metabolic Syndrome?

MedlinePlus

... 22, 2012 | News Release NIH launches trial to evaluate anti-inflammatory treatment for preventing heart attacks, strokes, ... and Usage No FEAR Act Grants and Funding Customer Service/Center for Health Information Email Alerts Jobs ...

The Efficacy of Prophylactic Antibiotics on Post-Stroke Infections: An Updated Systematic Review and Meta-Analysis

PubMed Central

Liu, Liang; Xiong, Xiao-Yi; Zhang, Qin; Fan, Xiao-Tang; Yang, Qing-Wu

2016-01-01

Post-stroke infections are common complications in acute stroke patients and are associated with an unfavorable functional outcome. However, reports on the effects of prophylactic antibiotics treatment on post-stroke infections are conflicting, especially those on post-stroke pneumonia and outcomes. We searched the PubMed, Embase, and Web of Knowledge databases up through March 11th, 2016. Seven randomized controlled trials including 4261 patients were analyzed among this systematic review and meta-analysis. We found preventive antibiotics treatment at the time of stroke onset did reduce the incidence of infections in adults with acute stroke (OR = 0.57, 95% CI: 0.38–0.85, P = 0.005), including reducing the number of urinary tract infections (OR = 0.34, 95% CI: 0.26–0.46, P < 0.001), but did not significantly decrease the rate of post-stroke pneumonia (OR = 0.91, 95% CI: 0.73–1.13, P = 0.385). Importantly, antibiotics treatment also showed no significant effect on the number of fatalities among stroke patients (OR = 1.07, 95% CI: 0.90–1.26, P = 0.743) and functional outcome scores on the modified Rankin Scale (OR = 1.76, 95% CI: 0.86–3.63, p = 0.124). Our study indicated that preventive antibiotics treatment not reduced the rate of post-stroke pneumonia or mortality, even though decreased the risk of infections, especially urinary tract infections. Thus, preventive antibiotics treatment may not be recommended for acute stroke patients. PMID:27841284

Longitudinal association between fasting blood glucose concentrations and first stroke in hypertensive adults in China: effect of folic acid intervention.

PubMed

Xu, Richard B; Kong, Xiangyi; Xu, Benjamin P; Song, Yun; Ji, Meng; Zhao, Min; Huang, Xiao; Li, Ping; Cheng, Xiaoshu; Chen, Fang; Zhang, Yan; Tang, Genfu; Qin, Xianhui; Wang, Binyan; Hou, Fan Fan; Dong, Qiang; Chen, Yundai; Yang, Tianlun; Sun, Ningling; Li, Xiaoying; Zhao, Lianyou; Ge, Junbo; Ji, Linong; Huo, Yong; Li, Jianping

2017-03-01

Background: Diabetes is a known risk factor for stroke, but data on its prospective association with first stroke are limited. Folic acid supplementation has been shown to protect against first stroke, but its role in preventing first stroke in diabetes is unknown. Objectives: This post hoc analysis of the China Stroke Primary Prevention Trial tested the hypotheses that the fasting blood glucose (FBG) concentration is positively associated with first stroke risk and that folic acid treatment can reduce stroke risk associated with elevated fasting glucose concentrations. Design: This analysis included 20,327 hypertensive adults without a history of stroke or myocardial infarction, who were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid ( n = 10,160) or 10 mg enalapril alone ( n = 10,167). Kaplan-Meier survival analysis and Cox proportionate hazard models were used to test the hypotheses with adjustment for pertinent covariables. Results: During a median treatment duration of 4.5 y, 616 participants developed a first stroke (497 ischemic strokes). A high FBG concentration (≥7.0 mmol/L) or diabetes, compared with a low FBG concentration (<5.0 mmol/L), was associated with an increased risk of first stroke (6.0% compared with 2.6%, respectively; HR: 1.9; 95% CI: 1.3, 2.8; P < 0.001). Folic acid treatment reduced the risk of stroke across a wide range of FBG concentrations ≥5.0 mmol/L, but risk reduction was greatest in subjects with FBG concentrations ≥7.0 mmol/L or with diabetes (HR: 0.66; 95% CI: 0.46, 0.97; P < 0.05). There was a significant interactive effect of FBG and folic acid treatment on first stroke ( P = 0.01). Conclusions: In Chinese hypertensive adults, an FBG concentration ≥7.0 mmol/L or diabetes is associated with an increased risk of first stroke; this increased risk is reduced by 34% with folic acid treatment. These findings warrant additional investigation. This trial was registered at clinicaltrials.gov as NCT00794885. © 2017 American Society for Nutrition.

A randomized controlled trial on rehabilitation through caregiver-delivered nurse-organized service programs for disabled stroke patients in rural china (the RECOVER trial): design and rationale.

PubMed

Yan, Lijing L; Chen, Shu; Zhou, Bo; Zhang, Jing; Xie, Bin; Luo, Rong; Wang, Ninghua; Lindley, Richard; Zhang, Yuhong; Zhao, Yi; Li, Xian; Liu, Xiao; Peoples, Nicholas; Bettger, Janet Prvu; Anderson, Craig; Lamb, Sarah E; Wu, Yangfeng; Shi, Jingpu

2016-10-01

Stroke is the leading cause of death and disability in rural China. For stroke patients residing in resource-limited rural areas, secondary prevention and rehabilitation are largely unavailable, and where present, are far below evidence-based standards. This study aims to develop and implement a simplified stroke rehabilitation program that utilizes nurses and family caregivers for service delivery, and evaluate its feasibility and effectiveness in rural China. This 2-year randomized controlled trial is being conducted in 2-3 county hospitals located in northwest, northeast, and southwest China. Eligible and consenting stroke inpatients (200 in total) have been recruited and randomized into either a control or intervention group. Nurses in the county hospital are trained by rehabilitation specialists and in turn train the family caregivers in the intervention group. They also provide telephone follow-up care three times post discharge. The recruitment, baseline, intervention, follow-up care, and evaluation are guided by the RECOVER mobile phone app specifically designed for this study. The primary outcome is patients' Barthel Index (activities of daily living: mobility, self-care, and toileting) at 6 months. Process and economic evaluation will also be conducted. The results of our study will generate initial high-quality evidence to improve stroke care in resource-scarce settings. If proven effective, this innovative care delivery model has the potential to improve the health and function of stroke patients, relieve caregiver burden, guide policy-making, and advance translational research in the field of stroke care. © 2016 World Stroke Organization.

Prevention of Decline in Cognition after Stroke Trial (PODCAST): a study protocol for a factorial randomised controlled trial of intensive versus guideline lowering of blood pressure and lipids

PubMed Central

2013-01-01

Background Stroke is a common cause of cognitive impairment and dementia. However, effective strategies for reducing the risk of post-stroke dementia remain undefined. Potential strategies include intensive lowering of blood pressure and/or lipids. Methods/Design Design: multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial phase IV trial in secondary and primary care. Participants: 100 participants from 30 UK Stroke Research Network sites who are post- ischemic stroke or intracerebral haemorrhage by three to seven months. Interventions - all patients (1:1): intensive versus guideline blood pressure lowering (target systolic < 125 mmHg versus < 140 mmHg). Interventions - ischemic stroke (1:1): intensive versus guideline lipid lowering (target low density lipoprotein-cholesterol (LDL-c) < 1.4 mmol/l versus < 3 mmol/l). Hypotheses: does ‘intensive’ blood pressure lowering therapy and/or ‘intensive’ lipid control reduce cognitive decline and dementia in people with ischemic stroke; and does ‘intensive’ blood pressure lowering therapy reduce cognitive decline and dementia in patients with hemorrhagic stroke. Primary outcome: Addenbrooke’s Cognitive Examination-Revised. Secondary outcomes: feasibility of recruitment and retention of participants, tolerability and safety of the interventions, achieving and maintaining the blood pressure and lipid targets, maintaining differences in systolic blood pressure (> 10 mmHg) and low density lipoprotein-cholesterol (> 1 mmol/l) between the treatment groups, and performing clinic and telephone follow-up of cognition measures. Randomisation: using stratification, minimization and simple randomization. Blinding: participants receive open-label management. Cognition is assessed both unblinded (in clinic) and blinded (by telephone) to treatment. Adjudication of events (dementia, vascular, serious adverse events) is blinded to management. Discussion The PODCAST trial is ongoing with 78 patients recruited to date from 22 sites. Outcomes of cognitive impairment and dementia are accruing. Trial registration ISRCTN85562386 PMID:24266960

Novel Oral Anticoagulants in Atrial Fibrillation: Update on Apixaban

PubMed Central

Mezue, Kenechukwu; Obiagwu, Chukwudi; John, Jinu; Sharma, Abhishek; Yang, Felix; Shani, Jacob

2017-01-01

Almost 800,000 new or recurrent strokes occur every year. Atrial fibrillation, the most common cardiac arrhythmia, is a major risk factor for stroke, accounting for 15-20% of ischemic strokes. Apixaban is a direct inhibitor of Factor Xa that was approved in December 2012 by the US Food and Drug Administration (FDA) for the prevention of stroke in patients with non-valvular atrial fibrillation. It is part of a family of novel oral anticoagulants (NOACs) which has advantage over warfarin of less dosing variability, rapid onset of action and no INR monitoring required. Apixaban showed superiority to warfarin in both primary efficacy and primary safety outcomes by simultaneously showing both significantly lower rates of strokes and systemic embolism and a reduced risk of major clinical bleeding in clinical trials. Warfarin remains the anticoagulant of choice for patients with prosthetic heart valves and significant mitral stenosis. There are currently no head-to-head studies that directly compare the different NOACs with one another, but it is expected that there will be more trials in the future that will explore this comparison. Dabigatran is the only NOAC with an FDA approved reversal agent. However, a reversal agent for apixaban is being developed and was successful in recent clinical trials. This review summarizes the clinical trial data on apixaban for atrial fibrillation, compares apixaban to other NOACs and discusses apixaban use in clinical practice. PMID:27450450

The cost savings of newer oral anticoagulants in atrial fibrillation-related stroke prevention
.

PubMed

Masbah, Norliana; Macleod, Mary Joan

2017-03-01

Newer oral anticoagulants (NOACs) are considered as better alternatives compared to warfarin for stroke prevention in atrial fibrillation (AF) in terms of clinical effectiveness although the drug acquisition cost is more substantial. This study determined the direct stroke costs based on inpatient hospitalization in a subgroup of the National Health Service (NHS) Grampian, Scotland, stroke patients, to evaluate the differences in costs related to AF stroke, and to ascertain whether the use of NOACs within this study population would produce greater cost savings. Hospitalization records over 5 years involving 3,601 stroke patients were analyzed. Direct costs were based on the costs of inpatient length of stay per day. The potential cost savings if AF patients had been on NOACs were estimated using efficacy data from a landmark clinical trial involving rivaroxaban. Out of the total stroke cases, 29.5% of total stroke cases were secondary to AF, and these cases were more severe with longer hospitalizations. Only 254 patients (39.4%) with confirmed AF were anticoagulated with warfarin prior to admission. AF patients incurred higher median costs (£4,719 (interquartile range (IQR) £1,815 - £12,452) compared to non-AF patients (£3,267 (IQR £1,175 - £11,368)), although the association was statistically insignificant. The use of NOACs in AF-related patients with ischemic strokes would potentially prevent more strokes (leading to 58 fewer cases in comparison to warfarin), resulting in 17.1% in total cost reduction. AF stroke patients incurred higher total direct costs compared to non-AF cases. However, more cost savings were evident with NOACs, due to more strokes being prevented through the use of NOACs compared to warfarin.
.

Potential Cost-Effectiveness of Ambulatory Cardiac Rhythm Monitoring After Cryptogenic Stroke.

PubMed

Yong, Jean Hai Ein; Thavorn, Kednapa; Hoch, Jeffrey S; Mamdani, Muhammad; Thorpe, Kevin E; Dorian, Paul; Sharma, Mike; Laupacis, Andreas; Gladstone, David J

2016-09-01

Prolonged ambulatory ECG monitoring after cryptogenic stroke improves detection of covert atrial fibrillation, but its long-term cost-effectiveness is uncertain. We estimated the cost-effectiveness of noninvasive ECG monitoring in patients aged ≥55 years after a recent cryptogenic stroke and negative 24-hour ECG. A Markov model used observed rates of atrial fibrillation detection and anticoagulation from a randomized controlled trial (EMBRACE) and the published literature to predict lifetime costs and effectiveness (ischemic strokes, hemorrhages, life-years, and quality-adjusted life-years [QALYs]) for 30-day ECG (primary analysis) and 7-day or 14-day ECG (secondary analysis), when compared with a repeat 24-hour ECG. Prolonged ECG monitoring (7, 14, or 30 days) was predicted to prevent more ischemic strokes, decrease mortality, and improve QALYs. If anticoagulation reduced stroke risk by 50%, 30-day ECG (at a cost of USD $447) would be highly cost-effective ($2000 per QALY gained) for patients with a 4.5% annual ischemic stroke recurrence risk. Cost-effectiveness was sensitive to stroke recurrence risk and anticoagulant effectiveness, which remain uncertain, especially at higher costs of monitoring. Shorter duration (7 or 14 days) monitoring was cost saving and more effective than an additional 24-hour ECG; its cost-effectiveness was less sensitive to changes in ischemic stroke risk and treatment effect. After a cryptogenic stroke, 30-day ECG monitoring is likely cost-effective for preventing recurrent strokes; 14-day monitoring is an attractive value alternative, especially for lower risk patients. These results strengthen emerging recommendations for prolonged ECG monitoring in secondary stroke prevention. Cost-effectiveness in practice will depend on careful patient selection. © 2016 American Heart Association, Inc.

Lap-tray and triangular sling are no more effective than a hemi-sling in preventing shoulder subluxation in those at risk early after stroke: a randomized trial.

PubMed

Ada, Louise; Foongchomcheay, Anchalee; Langhammer, Birgitta; Preston, Elisabeth; Stanton, Rosalyn; Robinson, John; Paul, Serene; Canning, Colleen

2017-02-01

Shoulder subluxation is a common secondary impairment of the upper limb following stroke. A range of supportive devices are used in rehabilitation to prevent shoulder subluxation, including hemi-slings and firm supports, such as arm troughs, however, there is little evidence regarding their efficacy. To determine whether a modified lap-tray during sitting and a triangular sling during standing is more effective than a hemi-sling in preventing shoulder subluxation, pain, contracture and upper limb activity limitation after stroke. A prospective, randomized trial with concealed allocation, assessor blinding and intention-to-treat analysis. Three inpatient rehabilitation units in Australia and Norway. Forty-six acute stroke survivors within 3 weeks of stroke who were at risk of subluxation. The experimental group used a modified lap-tray while sitting and a triangular sling while standing to support the affected arm for four weeks. The control group used a hemi-sling while sitting and standing. The primary outcome was amount of shoulder subluxation on X-ray. Secondary outcomes were upper limb activity, pain and contracture. There was no significant difference between groups in terms of shoulder subluxation (MD -3 mm, 95% CI -8 to 3). There was a trend for the experimental group to develop less pain at rest (MD -0.7 out of 10, 95% CI -2.2 to 0.8) and during shoulder external rotation (MD -1.7 out of 10, 95% CI -3.7 to 0.3) and a trend towards having less contracture of shoulder external rotation (MD -10 deg, 95% CI -22 to 2). There was no significant difference between groups in terms of other contractures and activity of the upper limb. A lap-tray during sitting combined with a triangular sling during standing is no more effective than a hemi-sling in preventing subluxation, pain, contracture and activity limitation in acute stroke survivors at risk of shoulder subluxation. The use of a lap-tray during sitting and triangular sling during standing is not indicated as an alternative to the hemi-sling to prevent shoulder subluxation in patients after stroke, so alternative strategies with proven efficacy, such as electrical stimulation, should be considered.

Quick reference guide to apixaban.

PubMed

Hurst, Katherine Victoria; O'Callaghan, John Matthew; Handa, Ashok

2017-01-01

Direct oral anticoagulants (DOACs) are being increasingly used in the clinical setting for patients at risk of venous thromboembolism (VTE) and/or stroke. These medications offer valued benefits for long-term use, including a fast onset of anticoagulation, fixed anticoagulation profile (and consequent prescription of specified doses) and no requirement for routine monitoring. Apixaban is a selective factor Xa inhibitor, approved for use in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of acute VTE. Like many of the DOACs, it has a fast onset of action and works to deliver predictable coagulation results. Multiple randomized controlled trials including ARISTOTLE and AMPLIFY have shown apixaban to be noninferior to vitamin K antagonists in the prevention of stroke and VTE, with a good safety profile. This article aims to review the use of apixaban for the prevention and treatment of thromboembolic disease, highlighting the key study results that have led to its current licensing and use.

Quick reference guide to apixaban

PubMed Central

Hurst, Katherine Victoria; O’Callaghan, John Matthew; Handa, Ashok

2017-01-01

Direct oral anticoagulants (DOACs) are being increasingly used in the clinical setting for patients at risk of venous thromboembolism (VTE) and/or stroke. These medications offer valued benefits for long-term use, including a fast onset of anticoagulation, fixed anticoagulation profile (and consequent prescription of specified doses) and no requirement for routine monitoring. Apixaban is a selective factor Xa inhibitor, approved for use in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of acute VTE. Like many of the DOACs, it has a fast onset of action and works to deliver predictable coagulation results. Multiple randomized controlled trials including ARISTOTLE and AMPLIFY have shown apixaban to be noninferior to vitamin K antagonists in the prevention of stroke and VTE, with a good safety profile. This article aims to review the use of apixaban for the prevention and treatment of thromboembolic disease, highlighting the key study results that have led to its current licensing and use. PMID:28744136

Efficacy and safety of left atrial appendage closure versus medical treatment in atrial fibrillation: a network meta-analysis from randomised trials.

PubMed

Sahay, Shweta; Nombela-Franco, Luis; Rodes-Cabau, Josep; Jimenez-Quevedo, Pilar; Salinas, Pablo; Biagioni, Corina; Nuñez-Gil, Ivan; Gonzalo, Nieves; de Agustín, Jose Alberto; Del Trigo, Maria; Perez de Isla, Leopoldo; Fernández-Ortiz, Antonio; Escaned, Javier; Macaya, Carlos

2017-01-15

The effectiveness of vitamin K antagonist (VKA) versus placebo and antiplatelet therapy (APT) is well established for stroke prevention in atrial fibrillation (AF). Non-vitamin K antagonist oral anticoagulants (NOAC) are mostly superior to VKA in stroke and intracranial bleeding prevention. Recent randomised controlled trials (RCTs) suggested the non-inferiority of percutaneous left atrial appendage closure (LAAC) versus VKA. However, comparisons between LAAC versus placebo, APT or NOAC are lacking. The purpose of this network meta-analysis was to assess the efficacy and safety of LAAC compared with other strategies for stroke prevention in patients with AF. We pooled together all RCTs comparing warfarin with placebo, APT or NOAC in patients with AF using meta-analysis guidelines. Two major trials of LAAC were also included and a network meta-analysis was performed to compare the impact of LAAC on mortality, stroke/systemic embolism (SE) and major bleeding in relation to medical treatment. The network meta-analysis included 19 RCTs with a total of 87 831 patients with AF receiving anticoagulants, APT, placebo or LAAC. Indirect comparison with network meta-analysis using warfarin as the common comparator revealed efficacy benefit favouring LAAC as compared with placebo (mortality: HR 0.38, 95% CI 0.22 to 0.67, p<0.001; stroke/SE: HR 0.24, 95% CI 0.11 to 0.52, p<0.001) and APT (mortality: HR 0.58, 95% CI 0.37 to 0.91, p=0.0018; stroke/SE: HR 0.44, 95% CI 0.23 to 0.86, p=0.017) and similar to NOAC (mortality: HR 0.76, 95% CI 0.50 to 1.16, p=0.211; stroke/SE: HR 1.01, 95% CI 0.53 to 1.92, p=0.969). LAAC showed comparable rates of major bleeding when compared with placebo (HR 2.33, 95% CI 0.67 to 8.09, p=0.183), APT (HR 0.75, 95% CI 0.30 to 1.88, p=0.542) and NOAC (HR 0.80, 95% CI 0.33 to 1.94, p=0.615). The findings of this meta-analysis suggest that LAAC is superior to placebo and APT, and comparable to NOAC for preventing mortality and stroke or SE, with similar bleeding risk in patients with non-valvular AF. However, these results should be interpreted with caution and more studies are needed to further substantiate this advantage, in view of the wide CIs with some variables in the current meta-analysis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Stroke Caused by Atherosclerosis of the Major Intracranial Arteries

PubMed Central

Banerjee, Chirantan; Chimowitz, Marc I.

2017-01-01

Our goal in this review is to discuss the pathophysiology, diagnosis and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms “intracranial stenosis” and “intracranial atherosclerosis”. Reference sections of published randomized clinical trials and previously published reviews were searched for additional references. Intracranial atherosclerotic disease (ICAD) is a highly prevalent cause of stroke that is associated with a high risk of recurrent stroke. It is more prevalent among blacks, Hispanics and Asians compared with whites. Diabetes, hypertension, metabolic syndrome, smoking, hyperlipidemia and a sedentary lifestyle are the major modifiable risk factors associated with ICAD. Randomized clinical trials comparing aggressive management (dual antiplatelet treatment for 90 days followed by aspirin monotherapy and intensive management of vascular risk factors) with intracranial stenting plus aggressive medical management have shown medical management alone to be safer and more effective for preventing stroke. As such, aggressive medical management has become the standard of care for symptomatic patients with ICAD. Nevertheless, there are subgroups of patients who are still at high risk of stroke despite being treated with aggressive medical management. Future research should aim to establish clinical, serologic, and imaging biomarkers to identify high-risk patients, and clinical trials evaluating novel therapies should be focused on these patients. PMID:28154100

Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation.

PubMed

Lip, G Y H; Frison, L; Grind, M

2008-07-01

To test the hypothesis that stroke and systemic embolic events (SEE) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) III and V trials are different between paroxysmal and persistent atrial fibrillation (AF). Data analysis from two cohorts of patients enrolled in the prospective SPORTIF III and V clinical trials (n = 7329); 836 subjects (11.4%) with paroxysmal AF [mean age 70.1 years (SD = 9.5)] were compared with 6493 subjects with persistent AF for this ancillary study. The annual event rates for stroke/SEE are 1.73% for persistent AF and 0.93% for paroxysmal AF. In a multivariate analysis, after adjusting for stroke risk factors, gender and aspirin usage, the differences remained statistically significant with a higher hazard ratio (HR) for stroke/SEE in persistent AF [vs. paroxysmal AF, HR 1.87, 95% confidence interval (CI) 1.04-3.36; P = 0.037]. In 'high risk' patients (with >or=2 stroke risk factors) annual event rates for stroke/SEE were 2.08% for persistent AF and 1.27% for paroxysmal AF (adjusted HR = 1.68, 95% CI 0.91-3.1, P = 0.098). Elderly patients had annual event rates for stroke/SEE of 2.38% for persistent AF and 1.13% for paroxysmal AF (adjusted HR = 2.27, 95% CI 0.92-5.59, P = 0.075). Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate, compared with 0.61% for previous VKA takers (HR = 0.33, 95% CI 0.11-1.01, P = 0.052). In this large clinical trial cohort of anticoagulated AF patients, those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF, although both groups had broadly similar stroke risk factors. Subjects with paroxysmal AF at 'high risk' had stroke/SEE rates that were not significantly different to persistent AF subjects.

Pharmacogenetic Associations of β1-Adrenergic Receptor Polymorphisms With Cardiovascular Outcomes in the SPS3 Trial (Secondary Prevention of Small Subcortical Strokes).

PubMed

Magvanjav, Oyunbileg; McDonough, Caitrin W; Gong, Yan; McClure, Leslie A; Talbert, Robert L; Horenstein, Richard B; Shuldiner, Alan R; Benavente, Oscar R; Mitchell, Braxton D; Johnson, Julie A

2017-05-01

Functional polymorphisms (Ser49Gly and Arg389Gly) in ADRB1 have been associated with cardiovascular and β-blocker response outcomes. Herein we examined associations of these polymorphisms with major adverse cardiovascular events (MACE), with and without stratification by β-blocker treatment in patients with a history of stroke. Nine hundred and twenty-six participants of the SPS3 trial's (Secondary Prevention of Small Subcortical Strokes) genetic substudy with hypertension were included. MACE included stroke, myocardial infarction, and all-cause death. Kaplan-Meier and multivariable Cox regression analyses were used. Because the primary component of MACE was ischemic stroke, we tested the association of Ser49Gly with ischemic stroke among 41 475 individuals of European and African ancestry in the NINDS (National Institute of Neurological Disorders and Stroke) SiGN (Stroke Genetics Network). MACE was higher in carriers of the Gly49 allele than in those with the Ser49Ser genotype (10.5% versus 5.4%, log-rank P =0.005). Gly49 carrier status was associated with MACE (hazard ratio, 1.62; 95% confidence interval, 1.00-2.68) and ischemic stroke (hazard ratio, 1.81; 95% confidence interval, 1.01-3.23) in SPS3 and with small artery ischemic stroke (odds ratio, 1.14; 95% confidence interval, 1.03-1.26) in SiGN. In SPS3, β-blocker-treated Gly49 carriers had increased MACE versus non-β-blocker-treated individuals and noncarriers (hazard ratio, 2.03; 95% confidence interval, 1.20-3.45). No associations were observed with the Arg389Gly polymorphism. Among individuals with previous small artery ischemic stroke, the ADRB1 Gly49 polymorphism was associated with MACE, particularly small artery ischemic stroke, a risk that may be increased among β-blocker-treated individuals. Further research is needed to define β-blocker benefit among ischemic stroke patients by ADRB1 genotype. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306. © 2017 American Heart Association, Inc.

Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial: rationale and design

PubMed Central

Johnston, S. Claiborne; Easton, J. Donald; Farrant, Mary; Barsan, William; Battenhouse, Holly; Conwit, Robin; Dillon, Catherine; Elm, Jordan; Lindblad, Anne; Morgenstern, Lewis; Poisson, Sharon N.; Palesch, Yuko

2015-01-01

Background Ischemic stroke and other vascular outcomes occur in 10–20% of patients in the 3 months following a TIA or minor ischemic stroke, and many are disabling. The highest risk period for these outcomes is the early hours and days immediately following the ischemic event. Aspirin is the most common antithrombotic treatment used for these patients. Aim The aim of POINT is to determine whether clopidogrel plus aspirin taken <12 hours after TIA or minor ischemic stroke symptom onset is more effective in preventing major ischemic vascular events at 90 days in the high-risk, and acceptably safe, compared to aspirin alone. Design POINT is a prospective, randomized, double-blind, multicenter trial in patients with TIA or minor ischemic stroke. Subjects are randomized to clopidogrel (600 mg loading dose followed by 75 mg/day) or matching placebo, and all will receive open-label aspirin 50–325 mg/day, with a dose of 162 mg daily for 5 days followed by 81 mg daily strongly recommended. Study Outcomes The primary efficacy outcome is the composite of new ischemic vascular events: ischemic stroke, myocardial infarction or ischemic vascular death, by 90 days. The primary safety outcome is major hemorrhage, which includes symptomatic intracranial hemorrhage. Discussion Aspirin is the most common antithrombotic given to patients with a stroke or TIA as it reduces the risk subsequent of stroke. This trial expects to determine whether more aggressive antithrombotic therapy with clopidogrel plus aspirin, initiated acutely, is more effective than aspirin alone. PMID:23879752

Reducing the psychosocial impact of aphasia on mood and quality of life in people with aphasia and the impact of caregiving in family members through the Aphasia Action Success Knowledge (Aphasia ASK) program: study protocol for a randomized controlled trial.

PubMed

Worrall, Linda; Ryan, Brooke; Hudson, Kyla; Kneebone, Ian; Simmons-Mackie, Nina; Khan, Asaduzzaman; Hoffmann, Tammy; Power, Emma; Togher, Leanne; Rose, Miranda

2016-03-22

People with aphasia and their family members are at high risk of experiencing post stroke depression. The impact of early interventions on mood and quality of life for people with aphasia is unknown. This study will determine whether an early intervention for both the person with aphasia after stroke and their family members leads to better mood and quality of life outcomes for people with aphasia, and less caregiver burden and better mental health for their family members. This is a multicenter, cluster-randomized controlled trial. Clusters, which are represented by Health Service Districts, will be randomized to the experimental intervention (Aphasia Action Success Knowledge Program) or an attention control (Secondary Stroke Prevention Information Program). People with aphasia and their family members will be blinded to the study design and treatment allocation (that is, will not know there are two arms to the study). Both arms of the study will receive usual care in addition to either the experimental or the attention control intervention. A total of 344 people with aphasia and their family members will be recruited. Considering a cluster size of 20, the required sample size can be achieved from 18 clusters. However, 20 clusters will be recruited to account for the potential of cluster attrition during the study. Primary outcome measures will be mood and quality of life of people with aphasia at 12 months post stroke. Secondary measures will be family member outcomes assessing the impact of caregiving and mental health, and self-reported stroke risk-related behaviors of people with aphasia. This is the first known program tailored for people with aphasia and their family members that aims to prevent depression in people with aphasia by providing intervention early after the stroke. This trial is registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) as ACTRN12614000979651 . Date registered: 11 September 2014.

Prevention of Stroke with the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

PubMed

Bohula, Erin A; Wiviott, Stephen D; Giugliano, Robert P; Blazing, Michael A; Park, Jeong-Gun; Murphy, Sabina A; White, Jennifer A; Mach, Francois; Van de Werf, Frans; Dalby, Anthony J; White, Harvey D; Tershakovec, Andrew M; Cannon, Christopher P; Braunwald, Eugene

2017-12-19

Patients who experience an acute coronary syndrome are at heightened risk of recurrent ischemic events, including stroke. Ezetimibe improved cardiovascular outcomes when added to statin therapy in patients stabilized after acute coronary syndrome. We investigated the efficacy of the addition of ezetimibe to simvastatin for the prevention of stroke and other adverse cardiovascular events in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), with a focus on patients with a stroke before randomization. Patients who experienced acute coronary syndrome were randomized to a placebo/simvastatin or ezetimibe/simvastatin regimen and followed for a median of 6 years. Treatment efficacy was assessed for the entire population and by subgroups for the first and total (first and subsequent) events for the end points of stroke of any etiology, stroke subtypes, and the primary trial end point at 7 years. Of 18 144 patients, 641 (3.5%) experienced at least 1 stroke; most were ischemic (527, 82%). Independent predictors of stroke included prior stroke, older age, atrial fibrillation, congestive heart failure, diabetes mellitus, myocardial infarction, and renal dysfunction. There was a nonsignificant reduction in the first event of stroke of any etiology (4.2% versus 4.8%; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.73-1.00; P =0.052) with ezetimibe/simvastatin versus placebo/simvastatin, driven by a significant 21% reduction in ischemic stroke (3.4% versus 4.1%; HR, 0.79; 95% CI, 0.67-0.94; P =0.008) and a nonsignificant increase in hemorrhagic stroke (0.8% versus 0.6%; HR, 1.38; 95% CI, 0.93-2.04; P =0.11). Evaluating total events, including the first and all recurrent strokes, ezetimibe/simvastatin reduced stroke of any etiology (HR, 0.83; 95% CI, 0.70-0.98; P =0.029) and ischemic stroke (HR, 0.76; 95% CI, 0.63-0.91; P =0.003). Patients who had experienced a stroke prior to randomization were at a higher risk of recurrence and demonstrated an absolute risk reduction of 8.6% for stroke of any etiology (10.2% versus 18.8%; number needed to treat=12; HR, 0.60; 95% CI, 0.38-0.95; P =0.030) and 7.6% for ischemic stroke (8.7% versus 16.3%; number needed to treat=13; HR, 0.52; 95% CI, 0.31-0.86; P =0.011) with ezetimibe added to simvastatin therapy. The addition of ezetimibe to simvastatin in patients stabilized after acute coronary syndrome reduces the frequency of ischemic stroke, with a particularly large effect seen in patients with a prior stroke. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00202878. © 2017 American Heart Association, Inc.

Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Hoffman, Elaine B; Deenadayalu, Naveen; Ezekowitz, Michael D; Camm, A John; Weitz, Jeffrey I; Lewis, Basil S; Parkhomenko, Alexander; Yamashita, Takeshi; Antman, Elliott M

2014-03-15

Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045). This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cost-effectiveness of apixaban vs warfarin for secondary stroke prevention in atrial fibrillation

PubMed Central

Easton, J. Donald; Johnston, S. Claiborne; Kim, Anthony S.

2012-01-01

Objective: To compare the cost-effectiveness of apixaban vs warfarin for secondary stroke prevention in patients with atrial fibrillation (AF). Methods: Using standard methods, we created a Markov decision model based on the estimated cost of apixaban and data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and other trials of warfarin therapy for AF. We quantified the cost and quality-adjusted life expectancy resulting from apixaban 5 mg twice daily compared with those from warfarin therapy targeted to an international normalized ratio of 2–3. Our base case population was a cohort of 70-year-old patients with no contraindication to anticoagulation and a history of stroke or TIA from nonvalvular AF. Results: Warfarin therapy resulted in a quality-adjusted life expectancy of 3.91 years at a cost of $378,500. In comparison, treatment with apixaban led to a quality-adjusted life expectancy of 4.19 years at a cost of $381,700. Therefore, apixaban provided a gain of 0.28 quality-adjusted life-years (QALYs) at an additional cost of $3,200, resulting in an incremental cost-effectiveness ratio of $11,400 per QALY. Our findings were robust in univariate sensitivity analyses varying model inputs across plausible ranges. In Monte Carlo analysis, apixaban was cost-effective in 62% of simulations using a threshold of $50,000 per QALY and 81% of simulations using a threshold of $100,000 per QALY. Conclusions: Apixaban appears to be cost-effective relative to warfarin for secondary stroke prevention in patients with AF, assuming that it is introduced at a price similar to that of dabigatran. PMID:22993279

Finding atrial fibrillation in stroke patients: Randomized evaluation of enhanced and prolonged Holter monitoring--Find-AF(RANDOMISED) --rationale and design.

PubMed

Weber-Krüger, Mark; Gelbrich, Götz; Stahrenberg, Raoul; Liman, Jan; Kermer, Pawel; Hamann, Gerhard F; Seegers, Joachim; Gröschel, Klaus; Wachter, Rolf

2014-10-01

Detecting paroxysmal atrial fibrillation (AF) in patients with ischemic strokes presenting in sinus rhythm is challenging because episodes are often short, occur randomly, and are frequently asymptomatic. If AF is detected, recurrent thromboembolism can be prevented efficiently by oral anticoagulation. Numerous uncontrolled studies using various electrocardiogram (ECG) devices have established that prolonged ECG monitoring increases the yield of AF detection, but most established procedures are time-consuming and costly. The few randomized trials are mostly limited to cryptogenic strokes. The optimal method, duration, and patient selection remain unclear. Repeated prolonged continuous Holter ECG monitoring to detect paroxysmal AF within an unspecific stroke population may prove to be a widely applicable, effective secondary prevention strategy. Find-AFRANDOMISED is a randomized and controlled prospective multicenter trial. Four hundred patients 60 years or older with manifest (symptoms ≥24 hours or acute computed tomography/magnetic resonance imaging lesion) and acute (symptoms ≤7 days) ischemic strokes will be included at 4 certified stroke centers in Germany. Those with previously diagnosed AF/flutter, indications/contraindications for oral anticoagulation, or obvious causative blood vessel pathologies will be excluded. Patients will be randomized 1:1 to either enhanced and prolonged Holter ECG monitoring (10 days at baseline and after 3 and 6 months) or standard of care (≥24-hour continuous ECG monitoring, according to current stroke guidelines). All patients will be followed up for at least 12 months. The primary end point is newly detected AF (≥30 seconds) after 6 months, confirmed by an independent adjudication committee. We plan to complete recruitment in autumn 2014. First results can be expected by spring 2016. Copyright © 2014 Mosby, Inc. All rights reserved.

Primary Prevention of Stroke in Chronic Kidney Disease Patients: A Scientific Update.

PubMed

Bilha, Stefana Catalina; Burlacu, Alexandru; Siriopol, Dimitrie; Voroneanu, Luminita; Covic, Adrian

2018-01-01

Although chronic kidney disease (CKD) is an independent risk factor for stroke, official recommendations for the primary prevention of stroke in CKD are generally lacking. We searched PubMed and ISI Web of Science for randomised controlled trials, observational studies, reviews, meta-analyses and guidelines referring to measures of stroke prevention or to the treatment of stroke-associated risk factors (cardiovascular disease in general and atrial fibrillation (AF), arterial hypertension or carotid artery disease in particular) among the CKD population. The use of oral anticoagulation in AF appears safe in non-end stage CKD, but it should be individualized and preferably based on thromboembolic and bleeding stratification algorithms. Non-vitamin K antagonist oral anticoagulants with definite dose adjustment are generally preferred over vitamin K antagonists in mild and moderate CKD and their indications have started being extended to severe CKD and dialysis also. Aspirin, but not clopidogrel, has limited indications for reducing the risk for atherothrombotic events in CKD due to its increased bleeding risk. Carotid endarterectomy has shown promising results for stroke risk reduction in CKD patients with high-grade symptomatic carotid stenosis. The medical treatment of arterial hypertension in CKD often fails to efficiently lower blood pressure values, but recent data regarding the use of interventional procedures such as renal denervation, baroreflex activation therapy or renal artery stenting are encouraging. Key Messages: In the absence of clear guidelines and protocols, primary prevention of stroke in CKD patients remains a subtle art in the hands of the clinicians. Nevertheless, refraining CKD patients from standard therapies often worsens their prognosis. © 2017 S. Karger AG, Basel.

Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype

PubMed Central

Traylor, Matthew; Adib-Samii, Poneh; Thijs, Vincent; Sudlow, Cathie; Rothwell, Peter M.; Boncoraglio, Giorgio; Dichgans, Martin; Meschia, James; Maguire, Jane; Levi, Christopher; Rost, Natalia S.; Rosand, Jonathan; Hassan, Ahamad; Bevan, Steve; Markus, Hugh S.

2016-01-01

Background and Purpose— Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels–associated genetic variant MTHFR C677T for association with magnetic resonance imaging–confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes. Methods— We included 1359 magnetic resonance imaging–confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status. Results— MTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30). Conclusions— MTHFR C677T was associated with magnetic resonance imaging–confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes. PMID:26839351

N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation).

PubMed

Hijazi, Ziad; Wallentin, Lars; Siegbahn, Agneta; Andersson, Ulrika; Christersson, Christina; Ezekowitz, Justin; Gersh, Bernard J; Hanna, Michael; Hohnloser, Stefan; Horowitz, John; Huber, Kurt; Hylek, Elaine M; Lopes, Renato D; McMurray, John J V; Granger, Christopher B

2013-06-04

This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels. Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases. In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors. Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, >1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p < 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p < 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p = 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p < 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level. NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

An update on surgical and medical management strategies for intracerebral hemorrhage.

PubMed

Kreitzer, Natalie; Adeoye, Opeolu

2013-11-01

Intracerebral hemorrhage (ICH) accounts for ∼ 10 to 15% of all strokes and is one of the major causes of stroke-related death and disability. After the initial hemorrhage, further bleeding and edema contribute to secondary damage and worsened outcomes. As such, goals of previous and ongoing trials are to prevent continued bleeding, as well as mitigate the impact of cerebral edema. Although no trials have shown a definite functional outcome benefit with a given intervention, much progress has been made recently. This review focuses on recent developments that inform the acute management of ICH. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Baseline Quality of Life and Risk of Stroke in the ALLHAT Study (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

PubMed

Shams, Tanzila; Auchus, Alexander P; Oparil, Suzanne; Wright, Clinton B; Wright, Jackson; Furlan, Anthony J; Sila, Cathy A; Davis, Barry R; Pressel, Sara; Yamal, Jose-Miguel; Einhorn, Paula T; Lerner, Alan J

2017-11-01

The visual analogue scale is a self-reported, validated tool to measure quality of life (QoL). Our purpose was to determine whether baseline QoL predicted strokes in the ALLHAT study (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) and evaluate determinants of poststroke change in QoL. In the ALLHAT study, among the 33 357 patients randomized to treatment arms, 1525 experienced strokes; 1202 (79%) strokes were nonfatal. This study cohort includes 32 318 (97%) subjects who completed the baseline visual analogue scale QoL estimate. QoL was measured on a visual analogue scale and adjusted using a Torrance transformation (transformed QoL [TQoL]). Kaplan-Meier curves and adjusted proportional hazards analyses were used to estimate the effect of TQoL on the risk of stroke, on a continuous scale (0-1) and by quartiles (≤0.81, >0.81≤0.89, >0.89≤0.95, >0.95). We analyzed the change from baseline to first poststroke TQoL using adjusted linear regression. After adjusting for multiple stroke risk factors, the hazard ratio for stroke events for baseline TQoL was 0.93 (95% confidence interval, 0.89-0.98) per 0.1 U increase. The lowest baseline TQoL quartile had a 20% increased stroke risk (hazard ratio=1.20 [95% confidence interval, 1.00-1.44]) compared with the reference highest quartile TQoL. Poststroke TQoL change was significant within all treatment groups ( P ≤0.001). Multivariate regression analysis revealed that baseline TQoL was the strongest predictor of poststroke TQoL with similar results for the untransformed QoL. The lowest baseline TQoL quartile had a 20% higher stroke risk than the highest quartile. Baseline TQoL was the only factor that predicted poststroke change in TQoL. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542. © 2017 American Heart Association, Inc.

Risk of recurrent stroke in patients with silent brain infarction in the PRoFESS Imaging Substudy

PubMed Central

Weber, Ralph; Weimar, Christian; Wanke, Isabel; Möller-Hartmann, Claudia; Gizewski, Elke R.; Blatchford, Jon; Hermansson, Karin; Demchuk, Andrew M.; Forsting, Michael; Sacco, Ralph L.; Saver, Jeffrey L.; Warach, Steven; Diener, Hans Christoph; Diehl, Anke

2012-01-01

Background and Purpose Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent non-cardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality. Methods The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age and sex matched stroke patients without SBI. Secondary outcomes were a combined vascular endpoint, other vascular events and mortality. The two groups were compared using conditional logistic regression. Results Silent brain infarction was detected in 207 (20.4%) patients of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (odds ratio 1.42, 95% confidence interval 0.79 to 2.56; p=0.24) during a mean follow-op of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI. Conclusion The presence of SBI in patients with recent mild non-cardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality. PMID:22267825

Adherence to a Healthy Nordic Diet and Risk of Stroke: A Danish Cohort Study.

PubMed

Hansen, Camilla Plambeck; Overvad, Kim; Kyrø, Cecilie; Olsen, Anja; Tjønneland, Anne; Johnsen, Søren Paaske; Jakobsen, Marianne Uhre; Dahm, Christina Catherine

2017-02-01

Specific dietary patterns, including the Mediterranean diet, have been associated with stroke prevention. Our aim was to investigate whether adherence to a healthy Nordic diet, including fish, apples and pears, cabbages, root vegetables, rye bread, and oatmeal, was associated with risk of stroke. Incident cases of stroke among 55 338 men and women from the Danish Diet, Cancer and Health cohort were identified from the Danish National Patient Register and verified by review of records. Cases of ischemic stroke were further subclassified based on etiology according to the TOAST classification system (Trial of Org 10172 in Acute Stroke Treatment). Information on diet was collected at baseline (1993-1997) using a semiquantitative food-frequency questionnaire. Cox proportional hazards models were used to estimate hazards ratios of total stroke and subtypes of ischemic and hemorrhagic stroke. During a median follow-up of 13.5 years, 2283 cases of incident stroke were verified, including 1879 ischemic strokes. Adherence to a healthy Nordic diet, as reflected by a higher Healthy Nordic Food Index score, was associated with a lower risk of stroke. The hazards ratio comparing an index score of 4 to 6 (high adherence) with an index score of 0 to 1 (low adherence) was 0.86 (95% confidence interval 0.76-0.98) for total stroke. Inverse associations were observed for ischemic stroke, including large-artery atherosclerosis. No trend was observed for hemorrhagic stroke; however, a statistically insignificant trend was observed for intracerebral hemorrhage. Our findings suggest that a healthy Nordic diet may be recommended for the prevention of stroke. © 2017 American Heart Association, Inc.

[Meta-analysis on effect of combined supplementation of folic acid, vitamin B12 and B6 on risk of cardio-cerebrovascular diseases in randomized control trials].

PubMed

Lan, X; Dang, S N; Zhao, Y L; Yan, H; Yan, H

2016-07-01

To evaluate the effect of the combined supplementation of folic acid, vitamin B12 and B6 on the risk of cardio-cerebrovascular diseases. The literatures of randomized control trials about the relationship between the combined supplementation of folic acid, vitamin B12 and B6 and risk of cardio-cerebrovascular diseases from 1980 to 2014 were retrieved, and the eligible studies were screened for a Meta-analysis. The study indicators were the incidences of cardiovascular disease events, myocardial infarction and stroke. The cffect indicators were relative risk(RR)and 95% confidence interval(CI). Jadad score was used for the quality evaluation of the trials used in the study. The literatures of 11 randomized control trials, involving 26 395 patients, were used in the Meta-analysis. The combined supplementation of B vitamins had no effect on the incidence of cardiovascular disease events(RR=1.00, 95% CI: 0.94-1.07)based on 8 studies. The combined supplementation of B vitamins had no effect on the incidence of myocardial infarction(RR= 1.03, 95% CI: 0.94-1.13)based on 9 studies. The combined supplementation of B vitamins could reduce the incidence of stroke by 14%(RR=0.86, 95%CI: 0.78-0.95)based on 9 studies. Compared with the control group, Taking folic acid combined with vitamin B12 and B6 could reduce the level of homocysteine by 2.53 μmol/L(95%CI:-3.93--1.12). Subgroup analysis indicated that the follow-up time, the dosage of folic acid and vitamin B12 and B6, the history of diseases had no confounding effect on the incidence of cardio-cerebrovascular disease events. But the subgroup analysis for stroke showed that with the extension of follow-up time, the supplementation of B vitamins could reduce the risk of stroke. The effect of folic acid and B12 in small dosage seemed more significant in the prevention of stroke, while the preventive effect of B6 increased with increasing dosage. The preventive effect of combined supplementation of B vitamins was more significant for the patients with a history of cardio-cerebrovascular diseases. Taking folic acid combined with vitamin B6 and B12 might have no significant effect on the incidences of cardio-cerebrovascular disease events and myocardial infarction, but could lower the risk of stroke and the level of homocysteine.

Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task Force.

PubMed

Whitlock, Evelyn P; Burda, Brittany U; Williams, Selvi B; Guirguis-Blake, Janelle M; Evans, Corinne V

2016-06-21

The balance between potential aspirin-related risks and benefits is critical in primary prevention. To evaluate the risk for serious bleeding with regular aspirin use in cardiovascular disease (CVD) primary prevention. PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (2010 through 6 January 2015), and relevant references from other reviews. Randomized, controlled trials; cohort studies; and meta-analyses comparing aspirin with placebo or no treatment to prevent CVD or cancer in adults. One investigator abstracted data, another checked for accuracy, and 2 assessed study quality. In CVD primary prevention studies, very-low-dose aspirin use (≤100 mg daily or every other day) increased major gastrointestinal (GI) bleeding risk by 58% (odds ratio [OR], 1.58 [95% CI, 1.29 to 1.95]) and hemorrhagic stroke risk by 27% (OR, 1.27 [CI, 0.96 to 1.68]). Projected excess bleeding events with aspirin depend on baseline assumptions. Estimated excess major bleeding events were 1.39 (CI, 0.70 to 2.28) for GI bleeding and 0.32 (CI, -0.05 to 0.82) for hemorrhagic stroke per 1000 person-years of aspirin exposure using baseline bleeding rates from a community-based observational sample. Such events could be greater among older persons, men, and those with CVD risk factors that also increase bleeding risk. Power to detect effects on hemorrhagic stroke was limited. Harms other than serious bleeding were not examined. Consideration of the safety of primary prevention with aspirin requires an individualized assessment of aspirin's effects on bleeding risks and expected benefits because absolute bleeding risk may vary considerably by patient. Agency for Healthcare Research and Quality.

The research on 3D printing fingerboard and the initial application on cerebral stroke patient's hand spasm.

PubMed

Wang, Kai; Shi, Yiting; He, Wen; Yuan, Jing; Li, Yuan; Pan, Xiaolin; Zhao, Cuilian

2018-06-26

To research the possibility of designing customized 3D printing fingerboard to apply to the limb rehabilitation of cerebral stroke patients as well as the prevention and treatment of finger spasm, through 3D printing technology. Taking 18 hospitalized cerebral stroke patients for example, through scanning, molding and printing, to make and wear 3D printing fingerboard for them, and then observe the compliance, main complaint, muscular tension of affected hand and changes on range of motion after they wear the fingerboard for 3 weeks and 3 months. Have acquired completed data from 13 patients. The time of them wearing the fingerboard every day varied from 1 to 8 h, and most of them reflected that they felt comfortable and there was no feeling of worsened pain or finger skin allergy. In addition, the patients' grip strength, hand function and range of motion improved by varying degrees while their muscular tensions declined by varying degrees. The tension and bending resistance of the fingerboard all met the patients' treatment requirements. With the advantages of being accurate and customized, 3D printing fingerboard can benefit patients fixing and orthopedic treatment, and even prevent and treat cerebral stroke patient's finger spasm. Trial registration The research topic has been registered in Chinese Clinic Trial Registry. Registration time: January 15, 2016. Registration topic: The Use of 3D Printing Technology in the Orthotic of Extremity Rehabilitation of Stroke Patient. Registration Number: ChiCTR-INR-16007774.

Glyburide is associated with attenuated vasogenic edema in stroke patients.

PubMed

Kimberly, W Taylor; Battey, Thomas W K; Pham, Ly; Wu, Ona; Yoo, Albert J; Furie, Karen L; Singhal, Aneesh B; Elm, Jordan J; Stern, Barney J; Sheth, Kevin N

2014-04-01

Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known. Using a case-control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the glyburide advantage in malignant edema and stroke-pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 (MMP-9) plasma level in large hemispheric stroke. We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial.

An assessment of the cost-effectiveness of magnetic resonance, including diffusion-weighted imaging, in patients with transient ischaemic attack and minor stroke: a systematic review, meta-analysis and economic evaluation.

PubMed

Wardlaw, Joanna; Brazzelli, Miriam; Miranda, Hector; Chappell, Francesca; McNamee, Paul; Scotland, Graham; Quayyum, Zahid; Martin, Duncan; Shuler, Kirsten; Sandercock, Peter; Dennis, Martin

2014-04-01

Patients with transient ischaemic attack (TIA) or minor stroke need rapid treatment of risk factors to prevent recurrent stroke. ABCD2 score or magnetic resonance diffusion-weighted brain imaging (MR DWI) may help assessment and treatment. Is MR with DWI cost-effective in stroke prevention compared with computed tomography (CT) brain scanning in all patients, in specific subgroups or as 'one-stop' brain-carotid imaging? What is the current UK availability of services for stroke prevention? Published literature; stroke registries, audit and randomised clinical trials; national databases; survey of UK clinical and imaging services for stroke; expert opinion. Systematic reviews and meta-analyses of published/unpublished data. Decision-analytic model of stroke prevention including on a 20-year time horizon including nine representative imaging scenarios. The pooled recurrent stroke rate after TIA (53 studies, 30,558 patients) is 5.2% [95% confidence interval (CI) 3.9% to 5.9%] by 7 days, and 6.7% (5.2% to 8.7%) at 90 days. ABCD2 score does not identify patients with key stroke causes or identify mimics: 66% of specialist-diagnosed true TIAs and 35-41% of mimics had an ABCD2 score of ≥ 4; 20% of true TIAs with ABCD2 score of < 4 had key risk factors. MR DWI (45 studies, 9078 patients) showed an acute ischaemic lesion in 34.3% (95% CI 30.5% to 38.4%) of TIA, 69% of minor stroke patients, i.e. two-thirds of TIA patients are DWI negative. TIA mimics (16 studies, 14,542 patients) make up 40-45% of patients attending clinics. UK survey (45% response) showed most secondary prevention started prior to clinic, 85% of primary brain imaging was same-day CT; 51-54% of patients had MR, mostly additional to CT, on average 1 week later; 55% omitted blood-sensitive MR sequences. Compared with 'CT scan all patients' MR was more expensive and no more cost-effective, except for patients presenting at > 1 week after symptoms to diagnose haemorrhage; strategies that triaged patients with low ABCD2 scores for slow investigation or treated DWI-negative patients as non-TIA/minor stroke prevented fewer strokes and increased costs. 'One-stop' CT/MR angiographic-plus-brain imaging was not cost-effective. Data on sensitivity/specificity of MR in TIA/minor stroke, stroke costs, prognosis of TIA mimics and accuracy of ABCD2 score by non-specialists are sparse or absent; all analysis had substantial heterogeneity. Magnetic resonance with DWI is not cost-effective for secondary stroke prevention. MR was most helpful in patients presenting at > 1 week after symptoms if blood-sensitive sequences were used. ABCD2 score is unlikely to facilitate patient triage by non-stroke specialists. Rapid specialist assessment, CT brain scanning and identification of serious underlying stroke causes is the most cost-effective stroke prevention strategy. The National Institute for Health Research Health Technology Assessment programme.

Pre-Stroke Use of Beta-Blockers Does Not Lower Post-Stroke Infection Rate: An Exploratory Analysis of the Preventive Antibiotics in Stroke Study.

PubMed

Westendorp, Willeke F; Vermeij, Jan-Dirk; Brouwer, Matthijs C; Roos, Y B W E M; Nederkoorn, Paul J; van de Beek, Diederik

2016-01-01

Stroke-associated infections occur frequently and are associated with unfavorable outcome. Previous cohort studies suggest a protective effect of beta-blockers (BBs) against infections. A sympathetic drive may increase immune suppression and infections. This study is aimed at investigating the association between BB treatment at baseline and post-stroke infection in the Preventive Antibiotics in Stroke Study (PASS), a prospective clinical trial. We performed an exploratory analysis in PASS, 2,538 patients with acute phase of stroke (24 h after onset) were randomized to ceftriaxone (intravenous, 2 g per day for 4 days) in addition to stroke unit care, or standard stroke unit care without preventive antibiotic treatment. All clinical data, including use of BBs, was prospectively collected. Infection was diagnosed by the treating physician, and independently by an expert panel blinded for all other data. Multivariable analysis was performed to investigate the relation between BB treatment and infection rate. Infection, as defined by the physician, occurred in 348 of 2,538 patients (14%). Multivariable analysis showed that the use of BBs at baseline was associated with the development of infection during clinical course (adjusted OR (aOR) 1.61, 95% CI 1.19-2.18; p < 0.01). BB use at baseline was also associated with the development of pneumonia (aOR 1.56, 95% CI 1.05-2.30; p = 0.03). Baseline BB use was not associated with mortality (aOR 1.14, 95% CI 0.84-1.53; p = 0.41) or unfavorable outcome at 3 months (aOR 1.10, 95% CI 0.89-1.35; p = 0.39). Patients treated with BBs prior to stroke have a higher rate of infection and pneumonia. © 2016 S. Karger AG, Basel.

Poloxamer 188 (P188) as an Adjunct in Prolonged Hypotensive Resuscitation

DTIC Science & Technology

2009-06-01

formulated product is exceptionally stable if kept free of oxygen. The FDA has approved use of 5 year old clinical supplies for Phase III trials if...for use in new clinical trials assuming it continues to meet specifications. The agent is subject to slow oxidation. This can be retarded or prevented...management of many diseases, including sickle cell disease, vascular disease, stroke, and cancer; clinical trials , involving more than 4,000 patients

Carotid artery stenting versus no stenting assisting thrombectomy for acute ischaemic stroke: protocol for a systematic review of randomised clinical trials with meta-analyses and trial sequential analyses.

PubMed

Steglich-Arnholm, Henrik; Holtmannspötter, Markus; Gluud, Christian; Krieger, Derk Wolfgang

2016-12-01

In patients with intracranial large vessel arterial occlusion, ipsilateral extracranial carotid artery occlusions or near-occlusions pose a significant hurdle in endovascular management of acute ischaemic stroke. Stenting of the carotid lesion may be beneficial in this situation to provide a stable access for introducing catheters through the carotid lesion into the intracranial vasculature and the target occlusion. Furthermore, carotid stenting may ensure ample blood flow for wash-out of clot material and reperfusion of the ischaemic penumbral tissue. However, antiplatelet therapy administered to prevent stent thrombosis and sudden increase in blood flow after reopening of the carotid lesion may increase the risk for intracranial haemorrhagic complications. This review aims to assess the benefits and harms of carotid stenting vs. no stenting assisting thrombectomy for acute ischaemic stroke. International and regional electronic databases will be searched to identify eligible randomised clinical trials. To identify further published, unpublished, or on-going and planned trials searches of Google Scholar, Worldwide Food and Drug Administrations, Worldwide Medicines Agencies, company homepages, reference lists, conference proceedings, and the Science Citation Index cited reference search index will be conducted. Manufacturers of relevant interventional equipment, authors, colleagues, and researchers active in the field will be contacted. No language restrictions will be applied to these searches. Randomised clinical trials will be included for assessing benefits and harms and quasi-randomised studies, and observational studies will be included for assessing harms of the intervention. Meta-analyses will be performed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, and Trial Sequential Analyses will be conducted to control the risk of random errors and prevent premature statements of superiority of the experimental or control intervention or premature statement of futility. The quality of the evidence will be evaluated with the Grading of Recommendations Assessment, Development, and Evaluation. This systematic review of carotid stenting in endovascular management of acute ischaemic stroke in patients with concomitant extracranial carotid lesions and intracranial embolism will assess benefits and harms of this intervention and assesses whether carotid stenting should be encouraged or avoided in acute ischaemic stroke and identify targets for further research. PROSPERO CRD42016033346.

Arterial stiffness and stroke: de-stiffening strategy, a therapeutic target for stroke

PubMed Central

Chen, Yajing; Shen, Fanxia; Liu, Jianrong; Yang, Guo-Yuan

2017-01-01

Stroke is the second leading cause of mortality and morbidity worldwide. Early intervention is of great importance in reducing disease burden. Since the conventional risk factors cannot fully account for the pathogenesis of stroke, it is extremely important to detect useful biomarkers of the vascular disorder for appropriate intervention. Arterial stiffness, a newly recognised reliable feature of arterial structure and function, is demonstrated to be associated with stroke onset and serve as an independent predictor of stroke incidence and poststroke functional outcomes. In this review article, different measurements of arterial stiffness, especially pressure wave velocity, were discussed. We explained the association between arterial stiffness and stroke occurrence by discussing the secondary haemodynamic changes. We reviewed clinical data that support the prediction role of arterial stiffness on stroke. Despite the lack of long-term randomised double-blind controlled therapeutic trials, it is high potential to reduce stroke prevalence through a significant reduction of arterial stiffness (which is called de-stiffening therapy). Pharmacological interventions or lifestyle modification that can influence blood pressure, arterial function or structure in either the short or long term are promising de-stiffening therapies. Here, we summarised different de-stiffening strategies including antihypertension drugs, antihyperlipidaemic agents, chemicals that target arterial remodelling and exercise training. Large and well-designed clinical trials on de-stiffening strategy are needed to testify the prevention effect for stroke. Novel techniques such as modern microscopic imaging and reliable animal models would facilitate the mechanistic analyses in pathophysiology, pharmacology and therapeutics. PMID:28959494

ICARUSS, the Integrated Care for the Reduction of Secondary Stroke trial: rationale and design of a randomized controlled trial of a multimodal intervention to prevent recurrent stroke in patients with a recent cerebrovascular event, ACTRN = 12611000264987.

PubMed

Joubert, J; Davis, S M; Hankey, G J; Levi, C; Olver, J; Gonzales, G; Donnan, G A

2015-07-01

The majority of strokes, both ischaemic and haemorrhagic, are attributable to a relatively small number of risk factors which are readily manageable in primary care setting. Implementation of best-practice recommendations for risk factor management is calculated to reduce stroke recurrence by around 80%. However, risk factor management in stroke survivors has generally been poor at primary care level. A model of care that supports long-term effective risk factor management is needed. To determine whether the model of Integrated Care for the Reduction of Recurrent Stroke (ICARUSS) will, through promotion of implementation of best-practice recommendations for risk factor management reduce the combined incidence of stroke, myocardial infarction and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. A prospective, Australian, multicentre, randomized controlled trial. Academic stroke units in Melbourne, Perth and the John Hunter Hospital, New South Wales. 1000 stroke survivors recruited as from March 2007 with a recent (<3 months) stroke (ischaemic or haemorrhagic) or a TIA (brain or eye). Randomization and data collection are performed by means of a central computer generated telephone system (IVRS). Exposure to the ICARUSS model of integrated care or usual care. The composite of stroke, MI or death from any vascular cause, whichever occurs first. Risk factor management in the community, depression, quality of life, disability and dementia. With 1000 patients followed up for a median of one-year, with a recurrence rate of 7-10% per year in patients exposed to usual care, the study will have at least 80% power to detect a significant reduction in primary end-points The ICARUSS study aims to recruit and follow up patients between 2007 and 2013 and demonstrate the effectiveness of exposure to the ICARUSS model in stroke survivors to reduce recurrent stroke or vascular events and promote the implementation of best practice risk factor management at primary care level. © 2015 World Stroke Organization.

Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: the Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF Trial).

PubMed

Bansilal, Sameer; Bloomgarden, Zachary; Halperin, Jonathan L; Hellkamp, Anne S; Lokhnygina, Yuliya; Patel, Manesh R; Becker, Richard C; Breithardt, Günter; Hacke, Werner; Hankey, Graeme J; Nessel, Christopher C; Singer, Daniel E; Berkowitz, Scott D; Piccini, Jonathan P; Mahaffey, Kenneth W; Fox, Keith A A

2015-10-01

The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial. We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non-central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding. The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS2 score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio [HR] 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively; interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09; interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72; interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients. The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A randomized controlled trial of very early rehabilitation in speech after stroke.

PubMed

Godecke, Erin; Armstrong, Elizabeth A; Rai, Tapan; Middleton, Sandy; Ciccone, Natalie; Whitworth, Anne; Rose, Miranda; Holland, Audrey; Ellery, Fiona; Hankey, Graeme J; Cadilhac, Dominique A; Bernhardt, Julie

2016-07-01

The efficacy of rehabilitation therapy for aphasia caused by stroke is uncertain. The Very Early Rehabilitation of Speech (VERSE) trial aims to determine if intensive prescribed aphasia therapy (VERSE) is more effective and cost saving than non-prescribed, intensive (usual care-plus) and non-intensive usual care (UC) therapy when started within 15 days of stroke onset and continued daily over four weeks. We hypothesize that aphasia therapy when started very early after stroke and delivered daily could enhance recovery of communication compared with UC. A total of 246 participants (82 per arm) will provide 80% power to detect a 4.4% improvement on aphasia quotient between VERSE and UC plus at a significance level of α = 0.05. Acute-care hospitals and accompanying rehabilitation services throughout Australia, 2014-2017. Three-arm, prospective, randomized, parallel group, open-label, blinded endpoint assessment (PROBE) trial. Acute stroke in previous 14 days and aphasia diagnosed by aphasia quotient (AQ) of the Western Aphasia Battery (WAB). Computer-generated blocked randomization procedure stratified by aphasia severity according to Western Aphasia Battery, to one of three arms. All participants receive UC-usual ward-based aphasia therapy. Arm 1: UC-no additional therapy; Arm 2: UC-plus usual ward-based therapy; Arm 3: VERSE therapy-a prescribed and structured aphasia therapy program. Arms 2 and 3 receive a total of 20 additional sessions (45-60 min, provided daily) of aphasia therapy. The additional intervention must be provided before day 50 post stroke. The aphasia quotient of Western Aphasia Battery at 12 weeks post stroke. Secondary outcomes include discourse measures, the Stroke and Aphasia Quality of Life Scale-39 and the Aphasia Depression Rating Scale at 12 and 26 weeks. Incremental cost-effectiveness ratios at 26 weeks will be reported. This trial is designed to test whether the intensive and prescribed VERSE intervention is effective in promoting maximum recovery and preventing costly health complications in a vulnerable population of survivors of stroke. It will also provide novel, prospective, aphasia specific cost-effectiveness data to guide future policy development for this population. © 2016 World Stroke Organization.

Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot 'Prevention of Decline in Cognition after Stroke Trial' (PODCAST) Randomised Controlled Trial.

PubMed

Bath, Philip M; Scutt, Polly; Blackburn, Daniel J; Ankolekar, Sandeep; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M; Ford, Gary A

2017-01-01

Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125-170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0-8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke's Cognitive Examination-Revised (ACE-R). We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1-48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference -10·6/-5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference -0·54/-0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison. In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. ISRCTN ISRCTN85562386.

Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis.

PubMed

Rink, Cameron; Christoforidis, Greg; Khanna, Savita; Peterson, Laura; Patel, Yojan; Khanna, Suchin; Abduljalil, Amir; Irfanoglu, Okan; Machiraju, Raghu; Bergdall, Valerie K; Sen, Chandan K

2011-11-01

Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo (n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume (P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory (P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke.

A post hoc evaluation of a sample size re-estimation in the Secondary Prevention of Small Subcortical Strokes study.

PubMed

McClure, Leslie A; Szychowski, Jeff M; Benavente, Oscar; Hart, Robert G; Coffey, Christopher S

2016-10-01

The use of adaptive designs has been increasing in randomized clinical trials. Sample size re-estimation is a type of adaptation in which nuisance parameters are estimated at an interim point in the trial and the sample size re-computed based on these estimates. The Secondary Prevention of Small Subcortical Strokes study was a randomized clinical trial assessing the impact of single- versus dual-antiplatelet therapy and control of systolic blood pressure to a higher (130-149 mmHg) versus lower (<130 mmHg) target on recurrent stroke risk in a two-by-two factorial design. A sample size re-estimation was performed during the Secondary Prevention of Small Subcortical Strokes study resulting in an increase from the planned sample size of 2500-3020, and we sought to determine the impact of the sample size re-estimation on the study results. We assessed the results of the primary efficacy and safety analyses with the full 3020 patients and compared them to the results that would have been observed had randomization ended with 2500 patients. The primary efficacy outcome considered was recurrent stroke, and the primary safety outcomes were major bleeds and death. We computed incidence rates for the efficacy and safety outcomes and used Cox proportional hazards models to examine the hazard ratios for each of the two treatment interventions (i.e. the antiplatelet and blood pressure interventions). In the antiplatelet intervention, the hazard ratio was not materially modified by increasing the sample size, nor did the conclusions regarding the efficacy of mono versus dual-therapy change: there was no difference in the effect of dual- versus monotherapy on the risk of recurrent stroke hazard ratios (n = 3020 HR (95% confidence interval): 0.92 (0.72, 1.2), p = 0.48; n = 2500 HR (95% confidence interval): 1.0 (0.78, 1.3), p = 0.85). With respect to the blood pressure intervention, increasing the sample size resulted in less certainty in the results, as the hazard ratio for higher versus lower systolic blood pressure target approached, but did not achieve, statistical significance with the larger sample (n = 3020 HR (95% confidence interval): 0.81 (0.63, 1.0), p = 0.089; n = 2500 HR (95% confidence interval): 0.89 (0.68, 1.17), p = 0.40). The results from the safety analyses were similar to 3020 and 2500 patients for both study interventions. Other trial-related factors, such as contracts, finances, and study management, were impacted as well. Adaptive designs can have benefits in randomized clinical trials, but do not always result in significant findings. The impact of adaptive designs should be measured in terms of both trial results, as well as practical issues related to trial management. More post hoc analyses of study adaptations will lead to better understanding of the balance between the benefits and the costs. © The Author(s) 2016.

[Scope of the latest RE-LY substudies: clinical implications].

PubMed

Ruiz-Giménez Arrieta, N

2012-03-01

The approval of the use of dabiatran in stroke prevention in patients with nonvalvular atrial fibrilation (NVAF) is based on the results of the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, one of the largest studies to date in this entity. In this trial, dabigatran showed similar safety and efficacy to warfarin in primary and secondary prevention of stroke in patients with AF. At a dose of 150 mg twice daily, dabigatran was superior to warfarin in the prevention of stroke or systemic embolism and the 110 mg dose twice daily showed similar efficacy and greater safety, given the lower incidence of hemorrhage. These results were consistently found in the various subanalyses, with some slight differences of interest for clinical practice. The ideal candidates for dabiatran are patients with NVAF suitable for cardioversion, who require short periods of anticoagulation, patients in remote geographical areas with difficulty in achieving good anticoagulation control or good control with anti-vitamin K treatment due to IRN fluctuations, and patients with a low risk of hemorrhage and a CHADS score ≥ 3 and/or with prior stroke, whenever there are no contraindications. The choice of dabigatran dose should be evaluated according to the patient's individual characteristics (caution must be exercised when prescribing this drug in the elderly and in renal insufficiency) and embolic and/or hemorrhagic risk. Studies of the long-term safety of this drug, pharmacoeconomic analyses in Spain and post-commercialization pharmacovigilance data are required before the definitive uses of this drug can be established. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Perinatal thrombosis: implications for mothers and neonates.

PubMed

O'Brien, Sarah H

2015-01-01

Stroke is more likely to occur in the perinatal period than any other time in childhood, and these events can lead to a lifetime of intellectual and motor disabilities, epilepsy, and behavioral challenges. This review describes the epidemiology and natural history of perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT), risk factors for these complications, recent evidence regarding treatment strategies, and current gaps in knowledge. Existing evidence demonstrates the multifactorial etiology of symptomatic ischemic stroke in neonates, which includes a combination of maternal, delivery, and neonatal factors. The importance of inherited thrombophilia in the pathophysiology and long-term outcomes of perinatal stroke requires additional study. At this time, there is no evidence to support routine extensive thrombophilia screening outside of a research setting. Despite the frequency of perinatal stroke and its association with substantial morbidity, treatment strategies are currently limited, and prevention strategies are nonexistent. Anticoagulation is rarely indicated in PAIS, and more work needs to focus on neuroprotective prevention and alternate treatment strategies. Anticoagulation does appear to be safe in CSVT and may prevent thrombus progression but clinical equipoise remains, and clinical trials are needed to obtain evidence regarding short- and long-term efficacy outcomes. © 2015 by The American Society of Hematology. All rights reserved.

The Indian consensus guidance on stroke prevention in atrial fibrillation: An emphasis on practical use of nonvitamin K oral anticoagulants.

PubMed

Dalal, Jamshed; Bhave, Abhay; Oomman, Abraham; Vora, Amit; Saxena, Anil; Kahali, Dhiman; Poncha, Fali; Gambhir, D S; Chaudhuri, Jaydip Ray; Sinha, Nakul; Ray, Saumitra; Iyengar, S S; Banerjee, Suvro; Kaul, Upendra

2015-12-01

The last ten years have seen rapid strides in the evolution of nonvitamin K oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF). For the preparation of this consensus, a comprehensive literature search was performed and data on available trials, subpopulation analyses, and case reports were analyzed. This Indian consensus document intends to provide guidance on selecting the right NOAC for the right patients by formulating expert opinions based on the available trials and Asian/Indian subpopulation analyses of these trials. A section has been dedicated to the current evidence of NOACs in the Asian population. Practical suggestions have been formulated in the following clinical situations: (i) Dose recommendations of the NOACs in different clinical scenarios; (ii) NOACs in patients with rheumatic heart disease (RHD); (iii) Monitoring anticoagulant effect of the NOACs; (iv) Overdose of NOACs; (v) Antidotes to NOACs; (vi) Treatment of hypertrophic cardiomyopathy (HCM) with AF using NOACs; (vii) NOACs dose in elderly, (viii) Switching between NOACs and vitamin K antagonists (VKA); (ix) Cardioversion or ablation in NOAC-treated patients; (x) Planned/emergency surgical interventions in patients currently on NOACs; (xi) Management of bleeding complications of NOACs; (xii) Management of acute coronary syndrome (ACS) in AF with NOACs; (xiii) Management of acute ischemic stroke while on NOACs. Copyright © 2015. Published by Elsevier B.V.

More outcomes than trials: a call for consistent data collection across stroke rehabilitation trials.

PubMed

Ali, M; English, C; Bernhardt, J; Sunnerhagen, K S; Brady, M

2013-01-01

Stroke survivors experience complex combinations of impairments, activity limitations, and participation restrictions. The essential components of stroke rehabilitation remain elusive. Determining efficacy in randomized controlled trials (RCTs) is challenging; there is no commonly agreed primary outcome measure for rehabilitation trials. Clinical guidelines depend on proof of efficacy in RCTs and meta-analyses. However, diverse trial aims, differing methods, inconsistent data collection, and use of multiple assessment tools hinder comparability across trials. Consistent data collection in acute stroke trials has facilitated meta-analyses to inform trial design and clinical practice. With few exceptions, inconsistent data collection has hindered similar progress in stroke rehabilitation research. There is an urgent need for the routine collection of a core dataset of common variables in rehabilitation trials. The European Stroke Organisation Outcomes Working Group, the National Institutes of Neurological Disorders and Stroke Common Data Elements project, and the Collaborative Stroke Audit and Research project have called for consistency in data collection in stroke trials. Standardizing data collection can decrease study start up times, facilitate data sharing, and inform clinical guidelines. Although achieving consensus on which outcome measures to use in stroke rehabilitation trials is a considerable task, perhaps a feasible starting point is to achieve consistency in the collection of data on demography, stroke severity, and stroke onset to inclusion times. Longer term goals could include the development of a consensus process to establish the core dataset. This should be endorsed by researchers, funders, and journal editors in order to facilitate sustainable change. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Left atrial appendage occlusion for prevention of stroke in nonvalvular atrial fibrillation: a meta-analysis.

PubMed

Bode, Weeranun D; Patel, Nikhil; Gehi, Anil K

2015-06-01

When anticoagulation for stroke prevention is contraindicated, left atrial appendage occlusion (LAAO) may be performed. Studies of LAAO have been limited by their small size, disparate patient populations, and lack of control group. Our purpose was to perform a meta-analysis of the safety and efficacy of LAAO in comparison with standard therapy for stroke prevention in nonvalvular AF. Due to the lack of a control group in studies of LAAO, data on stroke prevention from multiple large outcomes studies were used to produce a hypothetical control group based on clinical variables in the individual studies. Results were stratified according to LAAO device type. We identified 16 studies with a total of 1759 patients receiving LAAO. Summary estimates demonstrate LAAO reduced risk of stroke in comparison with no therapy or aspirin therapy [relative risk (RR), 0.34; 95 % CI, 0.25-0.46] and in comparison with warfarin therapy (RR, 0.65; 95 % CI, 0.46-0.91). Summary estimates differed based on the study used to derive the hypothetical control group. Device deployment was unsuccessful in 6.1 % of patients, and overall complication rate was 7.1 %. Efficacy and safety were similar across LAAO device type although a majority of patients in the meta-analysis received a Watchman device. Our data suggest that LAAO is a reasonable option for stroke prophylaxis in AF when anticoagulation is not an option, and the risk for stroke outweighs the risk of procedural complications. Data were limited with the use of most available devices. To better establish the risk and benefit of LAAO in comparison with standard therapy, more randomized controlled trials are necessary.

A strategy to reduce cardiovascular disease by more than 80%

PubMed Central

Wald, N J; Law, M R

2003-01-01

Objectives To determine the combination of drugs and vitamins, and their doses, for use in a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects. The strategy was to simultaneously reduce four cardiovascular risk factors (low density lipoprotein cholesterol, blood pressure, serum homocysteine, and platelet function) regardless of pretreatment levels. Design We quantified the efficacy and adverse effects of the proposed formulation from published meta-analyses of randomised trials and cohort studies and a meta-analysis of 15 trials of low dose (50-125 mg/day) aspirin. Outcome measures Proportional reduction in ischaemic heart disease (IHD) events and strokes; life years gained; and prevalence of adverse effects. Results The formulation which met our objectives was: a statin (for example, atorvastatin (daily dose 10 mg) or simvastatin (40 mg)); three blood pressure lowering drugs (for example, a thiazide, a β blocker, and an angiotensin converting enzyme inhibitor), each at half standard dose; folic acid (0.8 mg); and aspirin (75 mg). We estimate that the combination (which we call the Polypill) reduces IHD events by 88% (95% confidence interval 84% to 91%) and stroke by 80% (71% to 87%). One third of people taking this pill from age 55 would benefit, gaining on average about 11 years of life free from an IHD event or stroke. Summing the adverse effects of the components observed in randomised trials shows that the Polypill would cause symptoms in 8-15% of people (depending on the precise formulation). Conclusion The Polypill strategy could largely prevent heart attacks and stroke if taken by everyone aged 55 and older and everyone with existing cardiovascular disease. It would be acceptably safe and with widespread use would have a greater impact on the prevention of disease in the Western world than any other single intervention. PMID:12829553

Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention: A meta-analysis.

PubMed

Wang, Juan; Chen, Dan; Li, Da-Bing; Yu, Xin; Shi, Guo-Bing

2016-09-01

Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P < 0.00001) and an 18% reduction in RR (RR 0.82, 95% CI [0.73, 0.93], P = 0.002) in the subgroup without renal transplant recipients and patients undergoing regular hemodialysis separately. For the fatal stroke incidences, intensive-dose statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences.

Efficacy of a Chronic Care-Based Intervention on Secondary Stroke Prevention Among Vulnerable Stroke Survivors: A Randomized Controlled Trial.

PubMed

Cheng, Eric M; Cunningham, William E; Towfighi, Amytis; Sanossian, Nerses; Bryg, Robert J; Anderson, Thomas L; Barry, Frances; Douglas, Susan M; Hudson, Lillie; Ayala-Rivera, Monica; Guterman, Jeffrey J; Gross-Schulman, Sandra; Beanes, Sylvia; Jones, Andrea S; Liu, Honghu; Vickrey, Barbara G

2018-01-01

Disparities of care among stroke survivors are well documented. Effective interventions to improve recurrent stroke preventative care in vulnerable populations are lacking. In a randomized controlled trial, we tested the efficacy of components of a chronic care model-based intervention versus usual care among 404 subjects having an ischemic stroke or transient ischemic attack within 90 days of enrollment and receiving care within the Los Angeles public healthcare system. Subjects had baseline systolic blood pressure (SBP) ≥120 mm Hg. The intervention included a nurse practitioner/physician assistant care manager, group clinics, self-management support, report cards, decision support, and ongoing care coordination. Outcomes were collected at 3, 8, and 12 months, analyzed as intention-to-treat, and used repeated-measures mixed-effects models. Change in SBP was the primary outcome. Low-density lipoprotein reduction, antithrombotic medication use, smoking cessation, and physical activity were secondary outcomes. Average age was 57 years; 18% were of black race; 69% were of Hispanic ethnicity. Mean baseline SBP was 150 mm Hg in both arms. SBP decreased to 17 mm Hg in the intervention arm and 14 mm Hg in the usual care arm; the between-arm difference was not significant (-3.6 mm Hg; 95% confidence interval, -9.2 to 2.2). Among secondary outcomes, the only significant difference was that persons in the intervention arm were more likely to lower their low-density lipoprotein <100 md/dL (2.0 odds ratio; 95% confidence interval, 1.1-3.5). This intervention did not improve SBP control beyond that attained in usual care among vulnerable stroke survivors. A community-centered component could strengthen the intervention impact. URL: https://clinicaltrials.gov. Unique identifier: NCT00861081. © 2017 American Heart Association, Inc.

Blood pressure and stroke: an overview of published reviews.

PubMed

Lawes, Carlene M M; Bennett, Derrick A; Feigin, Valery L; Rodgers, Anthony

2004-04-01

The last few years have seen a considerable increase in the amount of information available concerning blood pressure (BP) and stroke associations. This article provides an overview of published reviews of the effects on stroke seen in trials of BP-lowering drugs and compares these with the results available from cohort studies. We present a review of major overviews of prospective cohort studies and an updated meta-analysis of >40 randomized controlled trials of BP lowering, which included >188 000 participants and approximately 6800 stroke events. Cohort studies now indicate that in the Asia Pacific region as well as in North America and Western Europe, each 10 mm Hg lower systolic BP is associated with a decrease in risk of stroke of approximately one third in subjects aged 60 to 79 years. The association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, and stroke subtypes and for fatal and nonfatal events. The proportional association is age dependent but is still strong and positive in those aged 80 years. Data from randomized controlled trials, in which mean age at event was approximately 70 years, indicate that a 10 mm Hg reduction in systolic BP is associated with a reduction in risk of stroke of approximately one third. Per mm Hg systolic BP reduction, the relative benefits for stroke appear similar between agents, by baseline BP levels, and whether or not individuals have a past history of cardiovascular disease. There is, however, evidence of greater benefit with a larger BP reduction. The epidemiologically expected benefits of BP lowering for stroke risk reduction are broadly consistent across a range of different population subgroups. There are greater benefits from larger BP reductions, and initiating and maintaining BP reduction for stroke prevention is a more important issue than choice of initial agent.

Acupuncture treatment for ischaemic stroke in young adults: protocol for a randomised, sham-controlled clinical trial

PubMed Central

Chen, Lifang; Fang, Jianqiao; Jin, Xiaoming; Keeler, Crystal Lynn; Gao, Hong; Fang, Zhen; Chen, Qin

2016-01-01

Introduction Stroke in young adults is not uncommon. Although the overall incidence of stroke has been recently declining, the incidence of stroke in young adults is increasing. Traditional vascular risk factors are the main cause of young ischaemic stroke. Acupuncture has been shown to benefit stroke rehabilitation and ameliorate the risk factors for stroke. The aims of this study were to determine whether acupuncture treatment will be effective in improving the activities of daily living (ADL), motor function and quality of life (QOL) in patients of young ischaemic stroke, and in preventing stroke recurrence by controlling blood pressure, lipids and body weight. Methods and analysis In this randomised, sham-controlled, participant-blinded and assessor-blinded clinical trial, 120 patients between 18 and 45 years of age with a recent (within 1 month) ischaemic stroke will be randomised for an 8-week acupuncture or sham acupuncture treatment. The primary outcome will be the Barthel Index for ADL. The secondary outcomes will include the Fugl-Meyer Assessment for motor function; the World Health Organization Quality of Life BREF (WHOQOL-BREF) for QOL; and risk factors that are measured by ambulatory blood pressure, the fasting serum lipid, body mass index and waist circumference. Incidence of adverse events and long-term mortality and recurrence rate during a 10-year and 30-year follow-up will also be investigated. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University. Protocol V.3 was approved in June 2013. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone during follow-up calls enquiring on the patient's post-study health status. Trial registration number ChiCTR-TRC- 13003317; Pre-results. PMID:26739742

Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED).

PubMed

Towfighi, Amytis; Cheng, Eric M; Ayala-Rivera, Monica; McCreath, Heather; Sanossian, Nerses; Dutta, Tara; Mehta, Bijal; Bryg, Robert; Rao, Neal; Song, Shlee; Razmara, Ali; Ramirez, Magaly; Sivers-Teixeira, Theresa; Tran, Jamie; Mojarro-Huang, Elizabeth; Montoya, Ana; Corrales, Marilyn; Martinez, Beatrice; Willis, Phyllis; Macias, Mireya; Ibrahim, Nancy; Wu, Shinyi; Wacksman, Jeremy; Haber, Hilary; Richards, Adam; Barry, Frances; Hill, Valerie; Mittman, Brian; Cunningham, William; Liu, Honghu; Ganz, David A; Factor, Diane; Vickrey, Barbara G

2017-02-06

Recurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population. In this single-blind randomized controlled trial, 516 adults (≥40 years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90 days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP <130 mmHg) at 1 year. Secondary outcomes include: (1) mean change in systolic BP; (2) control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial infarction (MI), and (7) cost-effectiveness of the intervention versus usual care. If this multi-component interdisciplinary intervention is shown to be effective in improving risk factor control after stroke, it may serve as a model that can be used internationally to reduce race/ethnic and socioeconomic disparities in stroke in resource-constrained settings. ClinicalTrials.gov Identifier NCT01763203 .

Paediatric stroke: pressing issues and promising directions.

PubMed

Kirton, Adam; deVeber, Gabrielle

2015-01-01

Stroke occurs across the lifespan with unique issues in the fetus, neonate, and child. The past decade has seen substantial advances in paediatric stroke research and clinical care, but many unanswered questions and controversies remain. The pathobiology of perinatal stroke needs to be better understood if prevention strategies are to be realised. Similarly, enhanced understanding of the mechanisms underlying childhood stroke, including cerebral arteriopathies, could inform the development of mechanism-specific treatments. Emerging clinical trials, including studies of neonatal sinovenous thrombosis and childhood arterial stroke, offer the hope of evidence-based treatment options in the near future. Early recognition of stroke in children is a key educational target for both the public and health-care professionals, and has translational potential to advance the application of neuroprotective, thrombolytic, and antithrombotic interventions and rehabilitation strategies to the earliest possible timepoints after stroke onset, improving outcomes and quality of life for affected children and their families. Copyright © 2015 Elsevier Ltd. All rights reserved.

Indications and applications of arterial stents for stroke prevention in atherosclerotic intracranial stenosis.

PubMed

Fields, Jeremy D; Liu, Kenneth C; Barnwell, Stanley L; Clark, Wayne M; Lutsep, Helmi L

2010-01-01

Intracranial stenosis accounts for 8-10% of all ischemic strokes in North America, a frequency slightly less than that of extracranial carotid stenosis. Among patients presenting with transient ischemic attack or stroke due to intracranial stenosis, the risk of recurrent stroke in the first year after initial symptoms is about 14%. Those with high-risk features (recent stroke and severe stenosis) have up to a 23% rate of recurrent stroke in the year after their initial event. Angioplasty with stenting has emerged as a potential treatment strategy, particularly in high-risk patients, although evidence is currently limited to uncontrolled prospective trials and retrospective case series. In this article, we critically review the clinical results supporting the use of stenting and highlight some key considerations in the application of this technology, including patient selection, procedural management, technical issues, and risk factors for complications and in-stent restenosis.

A Surgeon's View on Endarterectomy and Stenting in 2011: Lest We Forget, It's All About Preventing Stroke

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naylor, A. Ross, E-mail: ross.naylor@uhl-tr.nhs.uk

2012-04-15

It has been nearly 60 years since Felix Eastcott published his seminal paper on carotid reconstruction, which paved the way for carotid endarterectomy (CEA) and then carotid artery stenting (CAS) to assume prominent roles in the prevention of stroke. Yet the ensuing 60 years has witnessed repeated cycles of challenges to practice, professional mistrust, conflicts of interest, dogmatic retention of traditional management strategies, inappropriate corporate interventions, and a general failure to adapt to new evidence. Even the performance of large-scale randomised trials has been associated with rancour and a lack of consensus. This article reviews the history of invasive interventionsmore » in the treatment of carotid disease and makes a plea to both the surgical and interventional communities that the fundamental priority must always be the prevention of stroke. It concludes with an appeal for colleagues to collaborate to determine how best to treat patients during the hyperacute period after the onset of symptoms and to identify a smaller cohort of asymptomatic patients who are truly at high risk for stroke in whom to target CAS or CEA.« less

Telemedicine-guided education on secondary stroke and fall prevention following inpatient rehabilitation for Texas patients with stroke and their caregivers: a feasibility pilot study.

PubMed

Jhaveri, Mansi M; Benjamin-Garner, Ruby; Rianon, Nahid; Sherer, Mark; Francisco, Gerard; Vahidy, Farhaan; Kobayashi, Kayta; Gaber, Mary; Shoemake, Paige; Vu, Kim; Trevino, Alyssa; Grotta, James; Savitz, Sean

2017-09-03

The aftermath of stroke leaves many consequences including cognitive deficits and falls due to imbalance. Stroke survivors and families struggle to navigate the complex healthcare system with little assistance posthospital discharge, often leading to early hospital readmission and worse stroke outcomes. Telemedicine Guided Education on Secondary Stroke and Fall Prevention Following Inpatient Rehabilitation feasibility study examines whether stroke survivors and their caregivers find value in telerehabilitation (TR) home visits that provide individualised care and education by a multidisciplinary team after discharge from inpatient rehabilitation. A prospective, single arm, pilot study is designed to evaluate the feasibility of weekly TR home visits initiated postdischarge from inpatient rehabilitation. Newly diagnosed patients with stroke are recruited from a Houston-based comprehensive stroke centre inpatient rehabilitation unit, loaned an iPad with data plan and trained to use information technology security-approved videoconferencing application. After hospital discharge, six weekly TR home visits are led by rotating specialists (pharmacist, physical/occupational therapist, speech therapist, rehabilitation physician, social worker, geriatrician specialised in fracture prevention) followed by satisfaction survey on week 7. Specialists visually assess patients in real time, educate them on secondary stroke and fall prevention and suggest ways to improve function including direct medical interventions when indicated. Primary outcomes are proportion of eligible patients consenting to the study, participation rate in all six TR home visits and satisfaction score. The study started 31 December 2015 with plan to enrol up to 50 patients over 24 months. Feasibility study results will inform us as to whether a randomised controlled trial is warranted to determine efficacy of TR home visit intervention in improving stroke outcomes. Ethics approval obtained by the Institutional Review Board (IRB), Committee for the Protection of Human Subjects, IRB number: HSC-MS-14-0994. Study results will be submitted for publication in a peer-reviewed journal. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Inherited and Uncommon Causes of Stroke.

PubMed

Majersik, Jennifer Juhl

2017-02-01

This article is a practical guide to identifying uncommon causes of stroke and offers guidance for evaluation and management, even when large controlled trials are lacking in these rarer forms of stroke. Fabry disease causes early-onset stroke, particularly of the vertebrobasilar system; enzyme replacement therapy should be considered in affected patients. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), often misdiagnosed as multiple sclerosis, causes migraines, early-onset lacunar strokes, and dementia. Moyamoya disease can cause either ischemic or hemorrhagic stroke; revascularization is recommended in some patients. Cerebral amyloid angiopathy causes both microhemorrhages and macrohemorrhages, resulting in typical stroke symptoms and progressive dementia. Pregnancy raises the risk of both ischemic and hemorrhagic stroke, particularly in women with preeclampsia/eclampsia. Pregnant women are also at risk for posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome, and cerebral venous sinus thrombosis. Experts recommend that pregnant women with acute ischemic stroke not be systematically denied the potential benefits of IV recombinant tissue plasminogen activator. Neurologists should become familiar with these uncommon causes of stroke to provide future risk assessment and family counseling and to implement appropriate treatment plans to prevent recurrence.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

PubMed

Bousser, M G; Amarenco, P; Chamorro, A; Fisher, M; Ford, I; Fox, K; Hennerici, M G; Mattle, H P; Rothwell, P M

2009-01-01

Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event. Copyright 2009 S. Karger AG, Basel.

A qualitative study exploring patients' experiences of standard care or cardiac rehabilitation post minor stroke and transient ischaemic attack.

PubMed

Hillsdon, Kaye M; Kersten, Paula; Kirk, Hayden J S

2013-09-01

To explore individuals' experiences of receiving either standard care or comprehensive cardiac rehabilitation post minor stroke or transient ischaemic attack. A qualitative study using semi-structured interviews, alongside a randomized controlled trial, exploring the effectiveness of comprehensive cardiac rehabilitation compared with standard care. Interviews were transcribed verbatim and subjected to thematic analysis. Individuals' homes. People who have experienced a minor stroke or transient ischaemic attack and who were partaking in a secondary prevention randomized controlled trial (6-7 months post the event, 17 males, five females; mean age 67 years). Not relevant. Not relevant. Four themes were identified: information delivery, comparing oneself with others, psychological impact, attitudes and actions regarding risk factor reduction. Participants indicated a need for improved information delivery, specific to their own risk factors and lifestyle changes. Many experienced psychological impact as a result of their minor stroke. Participants were found to make two types of social comparison; the comparison of self to another affected by stroke, and the comparison of self to cardiac patients. Comprehensive cardiac rehabilitation was reported to have positive effects on people's motivation to exercise. Following a minor stroke, many individuals do not recall information given or risk factors specific to them. Downward comparison with individuals who have had a cardiovascular event led to some underplaying the significance of their minor stroke.

Glyburide is associated with attenuated vasogenic edema in stroke patients

PubMed Central

Kimberly, W. Taylor; Battey, Thomas W. K.; Pham, Ly; Wu, Ona; Yoo, Albert J.; Furie, Karen L.; Singhal, Aneesh B.; Elm, Jordan J.; Stern, Barney J.; Sheth, Kevin N.

2016-01-01

Background and Purpose Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 (SUR1) and transient receptor potential cation channel subfamily M member 4 (TRPM4). However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known. Methods Using a case control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the Glyburide Advantage in Malignant Edema and Stroke-Pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 plasma level in large hemispheric stroke. Results We report that IV glyburide was associated with attenuated T2 fluid attenuated inversion recovery (FLAIR) signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood matrix metalloproteinase-9 (MMP-9) level. Conclusions Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial. PMID:24072459

Impact of SAMMPRIS on the future of intracranial atherosclerotic disease management: polling results from the ICAD symposium at the International Stroke Conference.

PubMed

Zaidat, Osama O; Castonguay, Alicia C; Nguyen, Thanh N; Becker, Kyra J; Derdeyn, Colin P; Nelson, Peter K; Amarenco, Pierre; Brott, Thomas G

2014-04-01

There are few data regarding the effect of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial results on the management of intracranial atherosclerotic disease (ICAD). We sought to understand the impact of the SAMMPRIS trial on current ICAD clinical practices and future trial design. During the ICAD symposium at the 2012 International Stroke Conference, electronic data were collected regarding attendees' clinical management of ICAD and opinions on the feasibility of future trials post-SAMMPRIS. 217 attendees from different specialties, including neurologists (57%), neurointerventionalists (9%) and neurosurgeons (5%), participated in the session. The majority of respondents (77%) indicated that the results of SAMMPRIS have impacted their consideration for intracranial stenting. Post-SAMMPRIS, 84% selected 'SAMMPRIS-style' medical management for the treatment of ICAD. For patients with ICAD who failed aggressive medical therapy, 82% would consider an alternative approach to continuing medical therapy (30% considered clinical trial enrollment, 28% suggested angioplasty and stenting and 24% angioplasty). The majority of participants (85%) were willing to randomize patients with symptomatic ICAD in future trials. For the next ICAD trial, 29% indicated that angioplasty alone should be compared with aggressive medical therapy. Our polling results suggest that the SAMMPRIS trial has had an impact on the current treatment of ICAD. Treatment of patients who failed medical therapy varied widely from aggressive medical therapy to balloon angioplasty, stenting or enrollment in future clinical trials. The willingness to continue clinical trials and randomize patients supports the need for future ICAD studies.

Percutaneous closure of patent foramen ovale in patients with cryptogenic embolism: a network meta-analysis.

PubMed

Stortecky, Stefan; da Costa, Bruno R; Mattle, Heinrich P; Carroll, John; Hornung, Marius; Sievert, Horst; Trelle, Sven; Windecker, Stephan; Meier, Bernhard; Jüni, Peter

2015-01-07

Up to 40% of ischaemic strokes are cryptogenic. A strong association between cryptogenic stroke and the prevalence of patent foramen ovale (PFO) suggests paradoxical embolism via PFO as a potential cause. Randomized trials failed to demonstrate superiority of PFO closure over medical therapy. Randomized trials comparing percutaneous PFO closure against medical therapy or devices head-to-head published or presented by March 2013 were identified through a systematic search. We performed a network meta-analysis to determine the effectiveness and safety of PFO closure with different devices when compared with medical therapy. We included four randomized trials (2963 patients with 9309 patient-years). Investigated devices were Amplatzer (AMP), STARFlex (STF), and HELEX (HLX). Patients allocated to PFO closure with AMP were less likely to experience a stroke than patients allocated to medical therapy [rate ratio (RR) 0.39; 95% CI: 0.17-0.84]. No significant differences were found for STF (RR 1.01; 95% CI: 0.44-2.41), and HLX (RR, 0.71; 95% CI: 0.17-2.78) when compared with medical therapy. The probability to be best in preventing strokes was 77.1% for AMP, 20.9% for HLX, 1.7% for STF, and 0.4% for medical therapy. No significant differences were found for transient ischaemic attack and death. The risk of new-onset atrial fibrillation was more pronounced for STF (RR 7.67; 95% CI: 3.25-19.63), than AMP (RR 2.14; 95% CI: 1.00-4.62) and HLX (RR 1.33; 95%-CI 0.33-4.50), when compared with medical therapy. The effectiveness of PFO closure depends on the device used. PFO closure with AMP appears superior to medical therapy in preventing strokes in patients with cryptogenic embolism. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Dual antiplatelet therapy in stroke and ICAS: Subgroup analysis of CHANCE.

PubMed

Liu, Liping; Wong, Ka Sing Lawrence; Leng, Xinyi; Pu, Yuehua; Wang, Yilong; Jing, Jing; Zou, Xinying; Pan, Yuesong; Wang, Anxin; Meng, Xia; Wang, Chunxue; Zhao, Xingquan; Soo, Yannie; Johnston, S Claiborne; Wang, Yongjun

2015-09-29

AB OBJECTIVE: We aimed to investigate whether the efficacy and safety of clopidogrel plus aspirin vs aspirin alone were consistent between patients with and without intracranial arterial stenosis (ICAS), in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the interaction of the treatment effects of the 2 antiplatelet therapies among patients with and without ICAS, identified by magnetic resonance angiography (MRA) in CHANCE (ClinicalTrials.gov identifier NCT00979589). Overall, 1,089 patients with MRA images available in CHANCE were included in this subanalysis, 608 patients (55.8%) with ICAS and 481 (44.2%) without. Patients with ICAS had higher rates of recurrent stroke (12.5% vs 5.4%; p<0.0001) at 90 days than those without. But there was no statistically significant treatment by presence of ICAS interaction on either the primary outcome of any stroke (hazard ratio for clopidogrel plus aspirin vs aspirin alone: 0.79 [0.47-1.32] vs 1.12 [0.56-2.25]; interaction p=0.522) or the safety outcome of any bleeding event (interaction p=0.277). The results indicated higher rate of recurrent stroke in minor stroke or high-risk TIA patients with ICAS than in those without. However, there was no significant difference in the response to the 2 antiplatelet therapies between patients with and without ICAS in the CHANCE trial. Classification of evidence: This study provides Class II evidence that for patients with acute minor stroke or TIA with and without ICAS identified by MRA, clopidogrel plus aspirin is not significantly different than aspirin alone in preventing recurrent stroke. © 2015 American Academy of Neurology.

Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population [ISRCTN89345269

PubMed Central

Mant, Jonathan WF; Richards, Suzanne H; Hobbs, FD Richard; Fitzmaurice, David; Lip, Gregory YH; Murray, Ellen; Banting, Miriam; Fletcher, Kate; Rahman, Joy; Allan, Teresa; Raftery, James; Bryan, Stirling

2003-01-01

Background Atrial fibrillation (AF) is an important independent risk factor for stroke. Randomised controlled trials have shown that this risk can be reduced substantially by treatment with warfarin or more modestly by treatment with aspirin. Existing trial data for the effectiveness of warfarin are drawn largely from studies in selected secondary care populations that under-represent the elderly. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study will provide evidence of the risks and benefits of warfarin versus aspirin for the prevention of stroke for older people with AF in a primary care setting. Study design A randomised controlled trial where older patients with AF are randomised to receive adjusted dose warfarin or aspirin. Patients will be followed up at three months post-randomisation, then at six monthly intervals there after for an average of three years by their general practitioner. Patients will also receive an annual health questionnaire. 1240 patients will be recruited from over 200 practices in England. Patients must be aged 75 years or over and have AF. Patients will be excluded if they have a history of any of the following conditions: rheumatic heart disease; major non-traumatic haemorrhage; intra-cranial haemorrhage; oesophageal varices; active endoscopically proven peptic ulcer disease; allergic hypersensitivity to warfarin or aspirin; or terminal illness. Patients will also be excluded if the GP considers that there are clinical reasons to treat a patient with warfarin in preference to aspirin (or vice versa). The primary end-point is fatal or non-fatal disabling stroke (ischaemic or haemorrhagic) or significant arterial embolism. Secondary outcomes include major extra-cranial haemorrhage, death (all cause, vascular), hospital admissions (all cause, vascular), cognition, quality of life, disability and compliance with study medication. PMID:12939169

Closure of patent foramen ovale versus medical therapy after cryptogenic stroke.

PubMed

Carroll, John D; Saver, Jeffrey L; Thaler, David E; Smalling, Richard W; Berry, Scott; MacDonald, Lee A; Marks, David S; Tirschwell, David L

2013-03-21

Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age. In this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated. We enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased. In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270.).

Blood pressure and stroke: an overview of published reviews.

PubMed

Lawes, Carlene M M; Bennett, Derrick A; Feigin, Valery L; Rodgers, Anthony

2004-03-01

The last few years have seen a considerable increase in the amount of information available concerning blood pressure (BP) and stroke associations. This article provides an overview of published reviews of the effects on stroke seen in trials of BP-lowering drugs and compares these with the results available from cohort studies. We present a review of major overviews of prospective cohort studies and an updated meta-analysis of >40 randomized controlled trials of BP lowering, which included >188 000 participants and approximately 6800 stroke events. Cohort studies now indicate that in the Asia Pacific region as well as in North America and Western Europe, each 10 mm Hg lower systolic BP is associated with a decrease in risk of approximately one third in subjects aged 60 to 79 years. The association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, and stroke subtypes and for fatal and nonfatal events. The proportional association is age dependent but is still a strong and positive association in those aged 80 years. Data from randomized controlled trials, in which mean age at event was approximately 70 years, indicate that a 10 mm Hg reduction in systolic BP is associated with a reduction in risk of stroke of approximately one third. Per mm Hg systolic BP reduction, the benefits for stroke appear similar between agents, by baseline BP levels, and whether or not individuals have a past history of cardiovascular disease. There is, however, evidence of greater benefit with a larger BP reduction. The epidemiologically expected benefits of BP lowering for stroke risk reduction are broadly consistent across a range of different population subgroups. There are greater benefits from larger BP reductions, and initiating and maintaining BP reduction for stroke prevention is a more important issue than choice of initial agent.

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke.

PubMed

Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; Vandermaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-09-18

Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.) 2008 Massachusetts Medical Society

Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis

PubMed Central

Rink, Cameron; Christoforidis, Greg; Khanna, Savita; Peterson, Laura; Patel, Yojan; Khanna, Suchin; Abduljalil, Amir; Irfanoglu, Okan; Machiraju, Raghu; Bergdall, Valerie K; Sen, Chandan K

2011-01-01

Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo (n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume (P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory (P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke. PMID:21673716

PREVENTION OF CONVERSION TO ABNORMAL TCD WITH HYDROXYUREA IN SICKLE CELL ANEMIA: A PHASE III INTERNATIONAL RANDOMIZED CLINICAL TRIAL

PubMed Central

Hankins, Jane S.; McCarville, M. Beth; Rankine-Mullings, Angela; Reid, Marvin E.; Lobo, Clarisse L.C.; Moura, Patricia G.; Ali, Susanna; Soares, Deanne; Aldred, Karen; Jay, Dennis W.; Aygun, Banu; Bennett, John; Kang, Guolian; Goldsmith, Jonathan C.; Smeltzer, Matthew P.; Boyett, James M.; Ware, Russell E.

2015-01-01

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was an NHLBI-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ0-thalassemia (1), and HbSD (1), median age 5.4 years (range, 2.7-9.8)]. Due to slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI 0 to 35%) in the hydroxyurea arm and 47% (95% CI 6 to 81%) in observation arm at 15 months (p=0.16). In post-hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities, compared to observation (0% versus 50%, p=0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (−15.5 versus +10.2 cm/sec, p=0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. PMID:26414435

Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial.

PubMed

Hankins, Jane S; McCarville, Mary Beth; Rankine-Mullings, Angela; Reid, Marvin E; Lobo, Clarisse L C; Moura, Patricia G; Ali, Susanna; Soares, Deanne P; Aldred, Karen; Jay, Dennis W; Aygun, Banu; Bennett, John; Kang, Guolian; Goldsmith, Jonathan C; Smeltzer, Matthew P; Boyett, James M; Ware, Russell E

2015-12-01

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ(0) -thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7-9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0-35%) in the hydroxyurea arm and 47% (95% CI = 6-81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (-15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. © 2015 Wiley Periodicals, Inc.

Trends in Recruitment Rates for Acute Stroke Trials, 1990-2014.

PubMed

Feldman, William B; Kim, Anthony S; Chiong, Winston

2017-03-01

Slow recruitment in acute stroke trials hampers the evaluation of new therapies and delays the adoption of effective therapies into clinical practice. This systematic review evaluates whether recruitment efficiency and rates have increased in acute stroke trials from 1990 to 2014. Acute stroke trials from 2010 to 2014 were identified by a search of PubMed, Medline, the Cochrane Database of Research in Stroke, and the Stroke Trials Registry. These trials were compared to a previously published data set of trials conducted from 1990 to 2004. The median recruitment efficiency of trials from 1990 to 2004 was 0.41 participants/site/month compared with 0.26 participants/site/month from 2010 to 2014 ( P =0.14). The median recruitment rate of trials from 1990 to 2004 was 26.8 participants/month compared with 19.0 participants/month from 2010 to 2014 ( P =0.13). For acute stroke trials, neither recruitment efficiency nor recruitment rates have increased over the past 25 years and, if anything, have declined. © 2017 American Heart Association, Inc.

Increased work and social engagement is associated with increased stroke specific quality of life in stroke survivors at 3 months and 12 months post-stroke: a longitudinal study of an Australian stroke cohort.

PubMed

Tse, Tamara; Binte Yusoff, Siti Zubaidah; Churilov, Leonid; Ma, Henry; Davis, Stephen; Donnan, Geoffrey Alan; Carey, Leeanne M

2017-09-01

There is a relative lack of longitudinal studies investigating stroke-specific outcomes and quality of life (QOL). This study aimed to identify which factors (level of disability, cognitive functioning, depressive symptoms, physical activity, and work and social engagement) were independently associated with each stroke-specific domain of QOL, adjusting for age and gender, at 3 months and 12 months post-stroke in an Australian cohort. Survivors of ischemic stroke were recruited from 18 sites of the STroke imAging pRevention and Treatment (START) longitudinal cohort study. Survivors were assessed at 3 months (n = 185) and 12 months (n = 170) post-stroke using the Stroke Impact Scale (SIS), modified Rankin Scale (mRS), Montreal Cognitive Assessment (MoCA), Montgomery-Asberg Depression Rating Scale, Rapid Assessment of Physical Activity, and Work and Social Adjustment Scale (WSAS). WSAS was independently associated with the SIS domains of: Physical Composite function; Participation; and Perceived Recovery at 3 months and 12 months and SIS domain of Emotion at 12 months post-stroke. The presence of depressive symptoms was independently associated with the SIS domains of: Memory and Thinking; and Emotion at 3 months. At 12 months post-stroke, mRS was independently associated with SIS domain of Physical Composite function and MoCA with SIS domain of Communication. Engaging in work and social activities is an important factor associated with stroke-specific domains of QOL over time. It is recommended that services focus on improving work and social engagement given their importance related to QOL in the first year of recovery post-stroke. Identifying and treating those with depressive symptoms may enhance QOL in the early months post-stroke. START-PrePARE Australian New Zealand Clinical Trials, www.anzctr.org.au , Registry number: ACTRN12610000987066. EXTEND ClinicalTrial.gov identifier: NCT00887328.

30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial.

PubMed

Ringleb, P A; Allenberg, J; Brückmann, H; Eckstein, H-H; Fraedrich, G; Hartmann, M; Hennerici, M; Jansen, O; Klein, G; Kunze, A; Marx, P; Niederkorn, K; Schmiedt, W; Solymosi, L; Stingele, R; Zeumer, H; Hacke, W

2006-10-07

Carotid endarterectomy is effective in stroke prevention for patients with severe symptomatic carotid-artery stenosis, and carotid-artery stenting has been widely used as alternative treatment. Since equivalence or superiority has not been convincingly shown for either treatment, we aimed to compare the two. 1200 patients with symptomatic carotid-artery stenosis were randomly assigned within 180 days of transient ischaemic attack or moderate stroke (modified Rankin scale score of < or =3) carotid-artery stenting (n=605) or carotid endarterectomy (n=595). The primary endpoint of this hospital-based study was ipsilateral ischaemic stroke or death from time of randomisation to 30 days after the procedure. The non-inferiority margin was defined as less than 2.5% on the basis of an expected event rate of 5%. Analyses were on an intention-to-treat basis. This trial is registered at Current Controlled Trials with the international standard randomised controlled trial number ISRCTN57874028. 1183 patients were included in the analysis. The rate of death or ipsilateral ischaemic stroke from randomisation to 30 days after the procedure was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy (absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for non-inferiority is 0.09. SPACE failed to prove non-inferiority of carotid-artery stenting compared with carotid endarterectomy for the periprocedural complication rate. The results of this trial do not justify the widespread use in the short-term of carotid-artery stenting for treatment of carotid-artery stenoses. Results at 6-24 months are awaited.

Transition of patients from blinded study drug to open-label anticoagulation: the ENGAGE AF-TIMI 48 trial.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Mercuri, Michele; Curt, Valentin; Betcher, Joshua; Grip, Laura; Cange, Abby L; Crompton, Andrea E; Murphy, Sabina A; Deenadayalu, Naveen; Antman, Elliott M

2014-08-12

At the end of 2 previous trials, an excess of stroke and bleeding was observed in patients with AF randomized to a new oral anticoagulant (NOAC) who transitioned to a vitamin K antagonist (VKA). The ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial compared once-daily edoxaban to warfarin for stroke prevention in patients with AF. An end-of-trial transition plan was developed to minimize the risks of stroke due to inadequate anticoagulation and bleeding from excessive anticoagulation during this critical period. All patients on the blinded study drug at the trial's conclusion were included in this analysis. In pre-specified analyses, stroke, bleeding, and death that occurred through 30 days after the end-of-trial visit were stratified by randomized treatment allocation and open-label anticoagulant selected post-trial. Of the 13,642 patients taking the blinded study drug at the end of the trial, 9,304 (68.2%) were transitioned to open-label VKA and 4,258 patients (31.2%) to an NOAC. There were 21 strokes evenly distributed across the 3 randomized treatment arms: warfarin 7 (1.90%/year), edoxaban high dose 7 (1.89%/year), edoxaban low dose 7 (1.85%/year). Major bleeding was also similar across the 3 treatment arms: warfarin 11 (2.98%/year), edoxaban high dose 10 (2.69%/year), edoxaban low dose 18 (4.76%/year). In patients transitioned to VKA, 85% of patients had at least 1 INR ≥ 2 by day 14 after the transition and 99% by day 30. The ENGAGE AF-TIMI 48 transition plan protected patients from an excess of thrombotic and bleeding events and should be helpful in clinical practice when patients are transitioned between oral anticoagulants. (Global Study to Assess the Safety and Effectiveness of Edoxaban [DU-176b] vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation [EngageAFTIMI48]; NCT00781391). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: An updated systematic review and meta-analysis of randomized controlled trials.

PubMed

Ntaios, George; Papavasileiou, Vasileios; Diener, Hans-Chris; Makaritsis, Konstantinos; Michel, Patrik

2017-08-01

Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: "atrial fibrillation" and "anticoagulation" and "warfarin" and "previous stroke or transient ischemic attack." Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed to treat: 113) over 1.8-2.8 years. Conclusions This updated meta-analysis in 20,500 atrial fibrillation patients with previous stroke or transient ischemic attack shows that compared to warfarin non-vitamin-K antagonist oral anticoagulants are associated with a significant reduction of stroke, stroke or systemic embolism, hemorrhagic stroke, and intracranial bleeding.

Blood pressure as a prognostic factor after acute stroke.

PubMed

Tikhonoff, Valérie; Zhang, Haifeng; Richart, Tom; Staessen, Jan A

2009-10-01

Stroke is the second most common cause of death worldwide and is the complication of hypertension that is most directly linked to blood pressure. Hypertension affects nearly 30% of the world's population; therefore, reducing blood pressure is key for the prevention of stroke. Unlike the established role of hypertension as a risk factor for stroke, the prognostic importance of blood pressure in determining outcome after acute stroke is unclear. The acute hypertensive response occurs in more than 50% of all patients with acute stroke and is associated with poor prognosis. The relation between the outcome of acute stroke and blood pressure is U-shaped, with the best outcome at systolic blood-pressure levels ranging from about 140 to 180 mm Hg. The evidence that decreasing blood pressure in hypertensive patients with acute ischaemic or haemorrhagic stroke improves prognosis needs further confirmation. Whether raising blood pressure to improve perfusion of ischaemic brain areas is beneficial remains even more uncertain. Present guidelines for the management of blood pressure in patients with acute stroke are not evidence-based, but results from ongoing trials might provide more informed recommendations for the future.

Chinese medicines and bioactive compounds for treatment of stroke.

PubMed

Jayakumar, Thanasekaran; Elizebeth, Antoinet Ramola; Yen, Ting-lin; Sheu, Joen-rong

2015-02-01

Stroke is an important cause of mortality and morbidity worldwide but effective therapeutic strategy for the prevention of brain injury in patients with cerebral ischemia is lacking. Although tissue plasminogen activator has been used to treat stroke patients, this therapeutic strategy is confronted with ill side effects and is limited to patients within 3 h of a stroke. Due to the complexity of the events and the disappointing results from single agent trials, the combination of thrombolytic therapy and effective neural protection therapy may be an alternative strategy for patients with cerebral ischemia. Chinese medicine (CM) is the most widely practiced form of herbalism worldwide, as it is a sophisticated system of medical theory and practice that is specifically different from Western medicine. Most traditional therapeutic formulations consist of a combination of several drugs. The combination of multiple drugs is thought to maximize therapeutic efficacy by facilitating synergistic actions and preventing possible adverse effects while at the same time marking at multiple targets. CM has been labeled in ancient medicine systems as a treatment for various diseases associated with stroke. This review summarizes various CMs, bioactive compounds and their effects on cerebral ischemia.

A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial.

PubMed

Man-Son-Hing, M; Laupacis, A; O'Connor, A M; Biggs, J; Drake, E; Yetisir, E; Hart, R G

1999-08-25

Decision aids are tools designed to help patients participate in the clinical decision-making process. To determine whether use of an audiobooklet (AB) decision aid explaining the results of a clinical trial affected the decision-making process of study participants. Randomized controlled trial conducted from May 1997 to April 1998. Fourteen centers that participated in the Stroke Prevention in Atrial Fibrillation (SPAF) III trial. A total of 287 patients from the SPAF III aspirin cohort study, in which patients with atrial fibrillation and a relatively low risk of stroke received 325 mg/d of aspirin and were followed up for a mean of 2 years. At the end of SPAF III, participants were randomized to be informed of the study results with usual care plus use of an AB (AB group) vs usual care alone (control group). The AB included pertinent information to help patients decide whether to continue taking aspirin or switch to warfarin. Patients' ability to make choices regarding antithrombotic therapy, and 6-month adherence to these decisions. Their knowledge, expectations, decisional conflict (the amount of uncertainty about the course of action to take), and satisfaction with the decision-making process were also measured. More patients in the AB group made a choice about antithrombotic therapy than in the control group (99% vs 94%; P = .02). Patients in the AB group were more knowledgeable and had more realistic expectations about the risk of stroke and hemorrhage (in the AB group, 53%-80% correctly estimated different risks; in the control group, 16%-28% gave correct estimates). Decisional conflict and satisfaction were similar for the 2 groups. After 6 months, a similar percentage of patients were still taking their initial choice of antithrombotic therapy (95% vs 93%; P = .44). For patients with atrial fibrillation who had participated in a major clinical trial, the use of an AB decision aid improved their understanding of the benefits and risks associated with different treatment options and helped them make definitive choices about which therapy to take. Further studies are necessary to evaluate the acceptability and impact of decision aids in other clinical settings.

The early use of botulinum toxin in post-stroke spasticity: study protocol for a randomised controlled trial.

PubMed

Lindsay, Cameron; Simpson, Julie; Ispoglou, Sissi; Sturman, Steve G; Pandyan, Anand D

2014-01-08

Patients surviving stroke but who have significant impairment of function in the affected arm are at more risk of developing pain, stiffness and contractures. The abnormal muscle activity, associated with post-stroke spasticity, is thought to be causally associated with the development of these complications. Treatment of spasticity is currently delayed until a patient develops signs of these complications. This protocol is for a phase II study that aims to identify whether using OnabotulinumtoxinA (BoNT-A) in combination with physiotherapy early post stroke when initial abnormal muscle activity is neurophysiologically identified can prevent loss of range at joints and improve functional outcomes.The trial uses a screening phase to identify which people are appropriate to be included in a double blind randomised placebo-controlled trial. All patients admitted to Sandwell and West Birmingham NHS Trust Hospitals with a diagnosis of stroke will be screened to identify functional activity in the arm. Those who have no function will be appropriate for further screening. Patients who are screened and have abnormal muscle activity identified on EMG will be given electrical stimulation to forearm extensors for 3 months and randomised to have either injections of BoNT-A or normal saline. The primary outcome measure is the action research arm test - a measure of arm function. Further measures include spasticity, stiffness, muscle strength and fatigue as well as measures of quality of life, participation and caregiver strain. ISRCTN57435427, EudraCT2010-021257-39, NCT01882556.

The spot sign and tranexamic acid on preventing ICH growth--AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial.

PubMed

Meretoja, Atte; Churilov, Leonid; Campbell, Bruce C V; Aviv, Richard I; Yassi, Nawaf; Barras, Christen; Mitchell, Peter; Yan, Bernard; Nandurkar, Harshal; Bladin, Christopher; Wijeratne, Tissa; Spratt, Neil J; Jannes, Jim; Sturm, Jonathan; Rupasinghe, Jayantha; Zavala, Jorge; Lee, Andrew; Kleinig, Timothy; Markus, Romesh; Delcourt, Candice; Mahant, Neil; Parsons, Mark W; Levi, Christopher; Anderson, Craig S; Donnan, Geoffrey A; Davis, Stephen M

2014-06-01

No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation 'spot sign' will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4.5-hours of stroke onset compared with placebo. The Spot sign and Tranexamic acid On Preventing ICH growth--AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale >7, intracerebral hemorrhage volume <70 ml, no identified secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery) and demonstrating contrast extravasation on computed tomography angiography will receive either intravenous tranexamic acid 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo. A second computed tomography will be performed at 24 ± 3 hours to evaluate intracerebral hemorrhage growth and patients followed up for three-months. The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either >33% or >6 ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Diet and primary prevention of stroke: Systematic review and dietary recommendations by the ad hoc Working Group of the Italian Society of Human Nutrition.

PubMed

Iacoviello, L; Bonaccio, M; Cairella, G; Catani, M V; Costanzo, S; D'Elia, L; Giacco, R; Rendina, D; Sabino, P; Savini, I; Strazzullo, P

2018-04-01

To systematically review the latest evidence on established and emerging nutrition-related risk factors for incidence of and mortality from total, ischemic and haemorrhagic strokes. The present review was conducted in the framework of the work carried out through 2015 and 2016 for the preparation of the Italian Guidelines for the Prevention and Treatment of Stroke, 8th Edition, by ISO-SPREAD (Italian Stroke Organization and the Stroke Prevention and Educational Awareness Diffusion). Systematic review of articles focused on primary prevention of stroke published between January 2013 to May 2016 through an extensive search of the literature using MEDLINE/PUBMED, EMBASE and the Cochrane Library. Articles were ranked according to the SIGN methodology while the GRADE system was used to establish the strength of recommendations. As a result of our literature search, we examined 87 meta-analyses overall (mainly of prospective studies), a few isolated more recent prospective studies not included in the meta-analyses, and a smaller number of available randomized controlled trials and case-control studies. Based on the analysis of the above articles, 36 Syntheses of the available evidence and 36 Recommendations were eventually prepared. The present document was developed by organizing the available evidence into three individual areas (nutrients, food groups and dietary patterns) to provide a systematic and user-friendly overview of the available evidence on the relationship between nutrition and primary prevention of stroke. Yet analysis of foods and food patterns allowed translating the information about nutrients in a tool more amenable to use in daily life also in the light of the argument that people eat foods rather than nutrients. The present literature review and dietary recommendations provide healthcare professionals and all interested readers with a useful overview for the reduction of the risk of total, ischemic and haemorrhagic stroke through dietary modifications. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot ‘Prevention of Decline in Cognition after Stroke Trial’ (PODCAST) Randomised Controlled Trial

PubMed Central

Scutt, Polly; Blackburn, Daniel J.; Ankolekar, Sandeep; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M.; Ford, Gary A.

2017-01-01

Background Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. Methods In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125–170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0–8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke’s Cognitive Examination-Revised (ACE-R). Results We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1–48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference –10·6/–5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference –0·54/–0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison. Conclusion In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. Trial Registration ISRCTN ISRCTN85562386 PMID:28095412

Stroke Trials Registry

MedlinePlus

... Trials News About Neurology Image Library Search The Internet Stroke Center Trials Registry Clinical Trials Interventions Conditions ... UT Southwestern Medical Center. Copyright © 1997-2011 - The Internet Stroke Center. All rights reserved. The information contained ...

Cognitive rehabilitation for memory deficits following stroke.

PubMed

Majid, M J; Lincoln, N B; Weyman, N

2000-01-01

Memory problems occur following stroke. Cognitive rehabilitation programmes are provided to retrain memory function or to teach patients strategies to cope despite memory impairment. To determine the effects of cognitive rehabilitation for memory problems following stroke. We searched the Cochrane Stroke Group Trials Register, Medline, EMBASE, CINHAL and CLIN PSYCH databases and reference lists from relevant articles. Date of most recent searches: December 1998. Controlled trials of memory retraining in stroke. Studies with mixed aetiology groups were excluded unless they had more than 75% of stroke patients or separate data were available for the stroke patients. Two reviewers extracted trial data and assessed trial quality. Reviewers contacted investigators for further details of trials. One trial was identified with 12 participants. This showed memory strategy training had no significant effect on memory impairment or subjective memory complaints. There is insufficient evidence to support or refute the effectiveness of cognitive rehabilitation for memory problems after stroke.

Apixaban versus warfarin in patients with atrial fibrillation.

PubMed

Granger, Christopher B; Alexander, John H; McMurray, John J V; Lopes, Renato D; Hylek, Elaine M; Hanna, Michael; Al-Khalidi, Hussein R; Ansell, Jack; Atar, Dan; Avezum, Alvaro; Bahit, M Cecilia; Diaz, Rafael; Easton, J Donald; Ezekowitz, Justin A; Flaker, Greg; Garcia, David; Geraldes, Margarida; Gersh, Bernard J; Golitsyn, Sergey; Goto, Shinya; Hermosillo, Antonio G; Hohnloser, Stefan H; Horowitz, John; Mohan, Puneet; Jansky, Petr; Lewis, Basil S; Lopez-Sendon, Jose Luis; Pais, Prem; Parkhomenko, Alexander; Verheugt, Freek W A; Zhu, Jun; Wallentin, Lars

2011-09-15

Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).

Strokes with minor symptoms: an exploratory analysis of the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials.

PubMed

Khatri, Pooja; Kleindorfer, Dawn O; Yeatts, Sharon D; Saver, Jeffrey L; Levine, Steven R; Lyden, Patrick D; Moomaw, Charles J; Palesch, Yuko Y; Jauch, Edward C; Broderick, Joseph P

2010-11-01

The pivotal National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials excluded patients with ischemic stroke with specific minor presentations or rapidly improving symptoms. The recombinant tissue plasminogen activator product label notes that its use for minor neurological deficit or rapidly improving stroke symptoms has not been evaluated. As a result, patients with low National Institutes of Health Stroke Scale scores are not commonly treated in clinical practice. We sought to further characterize the patients with minor stroke who were included in the National Institute of Neurological Disorders and Stroke trials. Minor strokes were defined as National Institutes of Health Stroke Scale score ≤ 5 at baseline for this retrospective analysis, because this subgroup is most commonly excluded from treatment in clinical practice and trials. Clinical stroke syndromes were defined based on prespecified National Institutes of Health Stroke Scale item score clusters. Clinical outcomes were reviewed generally and within these cluster subgroups. Only 58 cases had National Institutes of Health Stroke Scale scores of 0 to 5 in the National Institute of Neurological Disorders and Stroke trials (42 recombinant tissue plasminogen activator and 16 placebo), and 2971 patients were excluded from the trials due to "rapidly improving" or "minor symptoms" as the primary reason. No patients were enrolled with isolated motor symptoms, isolated facial droop, isolated ataxia, dysarthria, isolated sensory symptoms, or with only symptoms/signs not captured by the National Institutes of Health Stroke Scale score (ie, National Institutes of Health Stroke Scale=0). There were ≤ 3 patients with each of the other isolated deficits enrolled in the trial. The National Institute of Neurological Disorders and Stroke trials excluded a substantial number of strokes with minor presentations, those that were included were small in number, and conclusions about outcomes based on specific syndromes cannot be drawn. Further prospective, systematic study of this subgroup is needed.

Novel oral anticoagulants for stroke prevention in patients with atrial fibrillation: dawn of a new era.

PubMed

Contractor, Tahmeed; Levin, Vadim; Martinez, Matthew W; Marchlinski, Francis E

2013-01-01

Atrial fibrillation (AF) is an important cause of ischemic stroke and is the underlying cause of > 20% of all strokes, with increasing age being a risk factor. Until recently, warfarin was the only available oral anticoagulant used to decrease this risk in patients with AF. However, there are several disadvantages of warfarin use, such as the requirement for monitoring the international normalized ratio, its wide range of drug-food interactions, and its narrow therapeutic index. Thus, there has been a strong impetus for the development of newer oral anticoagulants with predictable pharmacokinetics that obviate the need for monitoring the international normalized ratio. The US Food and Drug Administration has approved a direct thrombin inhibitor (dabigatran) and 2 factor Xa inhibitors (rivaroxaban and apixaban) for stroke prevention in patients with nonvalvular AF. There are several other new oral anticoagulant agents on the horizon, including the factor Xa inhibitor edoxaban. This review article discusses the pharmacological properties, clinical trial data, and practical issues associated with the use of these novel oral anticoagulants.

Stenting versus aggressive medical therapy for intracranial arterial stenosis.

PubMed

Chimowitz, Marc I; Lynn, Michael J; Derdeyn, Colin P; Turan, Tanya N; Fiorella, David; Lane, Bethany F; Janis, L Scott; Lutsep, Helmi L; Barnwell, Stanley L; Waters, Michael F; Hoh, Brian L; Hourihane, J Maurice; Levy, Elad I; Alexandrov, Andrei V; Harrigan, Mark R; Chiu, David; Klucznik, Richard P; Clark, Joni M; McDougall, Cameron G; Johnson, Mark D; Pride, G Lee; Torbey, Michel T; Zaidat, Osama O; Rumboldt, Zoran; Cloft, Harry J

2011-09-15

Atherosclerotic intracranial arterial stenosis is an important cause of stroke that is increasingly being treated with percutaneous transluminal angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has not been compared with medical management in a randomized trial. We randomly assigned patients who had a recent transient ischemic attack or stroke attributed to stenosis of 70 to 99% of the diameter of a major intracranial artery to aggressive medical management alone or aggressive medical management plus PTAS with the use of the Wingspan stent system. The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days. Enrollment was stopped after 451 patients underwent randomization, because the 30-day rate of stroke or death was 14.7% in the PTAS group (nonfatal stroke, 12.5%; fatal stroke, 2.2%) and 5.8% in the medical-management group (nonfatal stroke, 5.3%; non-stroke-related death, 0.4%) (P=0.002). Beyond 30 days, stroke in the same territory occurred in 13 patients in each group. Currently, the mean duration of follow-up, which is ongoing, is 11.9 months. The probability of the occurrence of a primary end-point event over time differed significantly between the two treatment groups (P=0.009), with 1-year rates of the primary end point of 20.0% in the PTAS group and 12.2% in the medical-management group. In patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected. (Funded by the National Institute of Neurological Disorders and Stroke and others; SAMMPRIS ClinicalTrials.gov number, NCT00576693.).

Mortality and morbidity during and after Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: results by sex.

PubMed

Oparil, Suzanne; Davis, Barry R; Cushman, William C; Ford, Charles E; Furberg, Curt D; Habib, Gabriel B; Haywood, L Julian; Margolis, Karen; Probstfield, Jeffrey L; Whelton, Paul K; Wright, Jackson T

2013-05-01

To determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in sex subgroups, we carried out a prespecified subgroup analysis of 15 638 women and 17 719 men in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Total follow-up (active treatment + passive surveillance using national administrative databases to ascertain deaths and hospitalizations) was 8 to 13 years. The primary outcome was fatal coronary heart disease or nonfatal myocardial infarction. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (coronary heart disease death, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. In-trial rates of HF, stroke, and combined cardiovascular disease were significantly higher for lisinopril compared with chlorthalidone, and rates of HF were significantly higher for amlodipine compared with chlorthalidone in both men and women. There were no significant treatment sex interactions. These findings did not persist through the extension period with the exception of the HF result for amlodipine versus chlorthalidone, which did not differ significantly by sex. For both women and men, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary coronary heart disease outcome or any other cardiovascular disease outcome, and chlorthalidone-based treatment resulted in the lowest risk of HF. Neither lisinopril nor amlodipine is superior to chlorthalidone for initial treatment of hypertension in either women or men. Clinical Trial Registration- clinicaltrials.gov; Identifier: NCT00000542.

ASPREE-NEURO study protocol: A randomized controlled trial to determine the effect of low-dose aspirin on cerebral microbleeds, white matter hyperintensities, cognition, and stroke in the healthy elderly.

PubMed

Ward, Stephanie A; Raniga, Parnesh; Ferris, Nicholas J; Woods, Robyn L; Storey, Elsdon; Bailey, Michael J; Brodtmann, Amy; Yates, Paul A; Donnan, Geoffrey A; Trevaks, Ruth E; Wolfe, Rory; Egan, Gary F; McNeil, John J

2017-01-01

Rationale Cerebral microbleeds seen on brain magnetic resonance imaging are markers of small vessel disease, linked to cognitive dysfunction and increased ischemic and hemorrhagic stroke risk. Observational studies suggest that aspirin use may induce cerebral microbleeds, and associated overt intracranial hemorrhage, but this has not been definitively resolved. Aims ASPREE-NEURO will determine the effect of aspirin on cerebral microbleed development over three years in healthy adults aged 70 years and over, participating in the larger 'ASPirin in Reducing Events in the Elderly (ASPREE)' primary prevention study of aspirin. Sample size Five hundred and fifty-nine participants provide 75% power (two-sided p value of 0.05) to determine an average difference of 0.5 cerebral microbleed per person after three years. Methods and design A multi-center, randomized placebo-controlled trial of 100 mg daily aspirin in participants who have brain magnetic resonance imaging at study entry, one and three years after randomization and who undergo cognitive testing at the same time points. Study outcomes The primary outcome is the number of new cerebral microbleeds on magnetic resonance imaging after three years. Secondary outcomes are the number of new cerebral microbleeds after one year, change in volume of white matter hyperintensity, cognitive function, and stroke. Discussion ASPREE-NEURO will resolve whether aspirin affects the presence and number of cerebral microbleeds, their relationship with cognitive performance, and indicate whether consideration of cerebral microbleeds alters the risk-benefit profile of aspirin in primary prevention for older people. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001313729.

Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force.

PubMed

Guirguis-Blake, Janelle M; Evans, Corinne V; Senger, Caitlyn A; O'Connor, Elizabeth A; Whitlock, Evelyn P

2016-06-21

Cardiovascular disease (CVD) is the leading cause of death in the United States. To update a systematic review about the benefits of aspirin for the primary prevention of cardiovascular events in adults aged 40 years or older and to evaluate effect modification in subpopulations. MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (January 2008 to January 2015), and Cochrane Database of Systematic Reviews. Two investigators independently reviewed 3396 abstracts and 65 articles according to prespecified criteria. All included trials evaluated aspirin for the primary prevention of cardiovascular events. Two investigators assessed study quality; data were abstracted by 1 reviewer and checked by a second. Two good-quality and 9 fair-quality randomized, controlled trials were identified. In analyses of all doses, aspirin reduced the risk for nonfatal myocardial infarction (MI) (relative risk [RR], 0.78 [95% CI, 0.71 to 0.87]) but not nonfatal stroke; aspirin showed little or no benefit for all-cause or cardiovascular mortality. Benefits began within the first 5 years. Older adults achieved greater relative MI reduction, but no other effect modifications were found in analyzed subpopulations. In trials with aspirin doses of 100 mg or less per day, the reduction in nonfatal MI benefit persisted (absolute risk reduction, 0.15 to 1.43 events per 1000 person-years) and a 14% reduction in nonfatal stroke benefit was noted, but no benefit was found for all-cause mortality (RR, 0.95 [CI, 0.89 to 1.01]) or cardiovascular mortality (RR, 0.97 [CI, 0.85 to 1.10]). Evidence for aspirin in primary prevention is heterogeneous and limited by rare events and few credible subgroup analyses. The beneficial effect of aspirin for the primary prevention of CVD is modest and occurs at doses of 100 mg or less per day. Older adults seem to achieve a greater relative MI benefit. Agency for Healthcare Research and Quality.

Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

PubMed

Fink, Howard A; Jutkowitz, Eric; McCarten, J Riley; Hemmy, Laura S; Butler, Mary; Davila, Heather; Ratner, Edward; Calvert, Collin; Barclay, Terry R; Brasure, Michelle; Nelson, Victoria A; Kane, Robert L

2018-01-02

Optimal treatment to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia is uncertain. To summarize current evidence on the efficacy and harms of pharmacologic interventions to prevent or delay cognitive decline, MCI, or dementia in adults with normal cognition or MCI. Several electronic databases from January 2009 to July 2017, bibliographies, and expert recommendations. English-language trials of at least 6 months' duration enrolling adults without dementia and comparing pharmacologic interventions with placebo, usual care, or active control on cognitive outcomes. Two reviewers independently rated risk of bias and strength of evidence; 1 extracted data, and a second checked accuracy. Fifty-one unique trials were rated as having low to moderate risk of bias (including 3 that studied dementia medications, 16 antihypertensives, 4 diabetes medications, 2 nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin, 17 hormones, and 7 lipid-lowering agents). In persons with normal cognition, estrogen and estrogen-progestin increased risk for dementia or a combined outcome of MCI or dementia (1 trial, low strength of evidence); high-dose raloxifene decreased risk for MCI but not for dementia (1 trial, low strength of evidence); and antihypertensives (4 trials), NSAIDs (1 trial), and statins (1 trial) did not alter dementia risk (low to insufficient strength of evidence). In persons with MCI, cholinesterase inhibitors did not reduce dementia risk (1 trial, low strength of evidence). In persons with normal cognition and those with MCI, these pharmacologic treatments neither improved nor slowed decline in cognitive test performance (low to insufficient strength of evidence). Adverse events were inconsistently reported but were increased for estrogen (stroke), estrogen-progestin (stroke, coronary heart disease, invasive breast cancer, and pulmonary embolism), and raloxifene (venous thromboembolism). High attrition, short follow-up, inconsistent cognitive outcomes, and possible selective reporting and publication. Evidence does not support use of the studied pharmacologic treatments for cognitive protection in persons with normal cognition or MCI. Agency for Healthcare Research and Quality.

Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?

PubMed

Go, Alan S; Hylek, Elaine M; Chang, Yuchiao; Phillips, Kathleen A; Henault, Lori E; Capra, Angela M; Jensvold, Nancy G; Selby, Joe V; Singer, Daniel E

2003-11-26

Warfarin has been shown to be highly efficacious for preventing thromboembolism in atrial fibrillation in randomized trials, but its effectiveness and safety in clinical practice is less clear. To evaluate the effect of warfarin on risk of thromboembolism, hemorrhage, and death in atrial fibrillation within a usual care setting. Cohort study assembled between July 1, 1996, and December 31, 1997, and followed up through August 31, 1999. Large integrated health care system in Northern California. Of 13,559 adults with nonvalvular atrial fibrillation, 11,526 were studied, 43% of whom were women, mean age 71 years, with no known contraindications to anticoagulation at baseline. Ischemic stroke, peripheral embolism, hemorrhage, and death according to warfarin use and comorbidity status, as determined by automated databases, review of medical records, and state mortality files. Among 11,526 patients, 397 incident thromboembolic events (372 ischemic strokes, 25 peripheral embolism) occurred during 25,341 person-years of follow-up, and warfarin therapy was associated with a 51% (95% confidence interval [CI], 39%-60%) lower risk of thromboembolism compared with no warfarin therapy (either no antithrombotic therapy or aspirin) after adjusting for potential confounders and likelihood of receiving warfarin. Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke. A nested case-control analysis estimated a 64% reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy. Warfarin was also associated with a reduced risk of all-cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial hemorrhage was uncommon, but the rate was moderately higher among those taking vs those not taking warfarin (0.46 vs 0.23 per 100 person-years, respectively; P =.003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However, warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage. The effects of warfarin were similar when patients with contraindications at baseline were analyzed separately or combined with those without contraindications (total cohort of 13,559). Warfarin is very effective for preventing ischemic stroke in patients with atrial fibrillation in clinical practice while the absolute increase in the risk of intracranial hemorrhage is small. Results of randomized trials of anticoagulation translate well into clinical care for patients with atrial fibrillation.

Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.

PubMed

Johnston, S Claiborne; Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Jonasson, Jenny; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence

2016-07-07

Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia. We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days. During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%. In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials.

PubMed

1994-07-11

Atrial fibrillation is associated with an increased risk of ischemic stroke. Data on individual patients were pooled from five recently completed randomized trials comparing warfarin (all studies) or aspirin (the Atrial Fibrillation, Aspirin, Anticoagulation Study and the Stroke Prevention in Atrial Fibrillation Study) with control in patients with atrial fibrillation. The purpose of the analysis was to (1) identify patient features predictive of a high or low risk of stroke, (2) assess the efficacy of antithrombotic therapy in major patient subgroups (eg, women), and (3) obtain the most precise estimate of the efficacy and risks of antithrombotic therapy in atrial fibrillation. For the warfarin-control comparison there were 1889 patient-years receiving warfarin and 1802 in the control group. For the aspirin-placebo comparison there were 1132 patient-years receiving aspirin and 1133 receiving placebo. The daily dose of aspirin was 75 mg in the Atrial Fibrillation, Aspirin, Anticoagulation Study and 325 mg in the Stroke Prevention in Atrial Fibrillation Study. To monitor warfarin dosage, three studies used prothrombin time ratios and two used international normalized ratios. The lowest target intensity was a prothrombin time ratio of 1.2 to 1.5 and the highest target intensity was an international normalized ratio of 2.8 to 4.2. The primary end points were ischemic stroke and major hemorrhage, as assessed by each study. At the time of randomization the mean age was 69 years and the mean blood pressure was 142/82 mm Hg. Forty-six percent of the patients had a history of hypertension, 6% had a previous transient ischemic attack or stroke, and 14% had diabetes. Risk factors that predicted stroke on multivariate analyses in control patients were increasing age, history of hypertension, previous transient ischemic attack or stroke, and diabetes. Patients younger than 65 years who had none of the other predictive factors (15% of all patients) had an annual rate of stroke of 1.0%, 95% confidence interval (CI) 0.3% to 3.0%. The annual rate of stroke was 4.5% for the control group and 1.4% for the warfarin group (risk reduction, 68%; 95% CI, 50% to 79%). The efficacy of warfarin was consistent across all studies and subgroups of patients. In women, warfarin decreased the risk of stroke by 84% (95% CI, 55% to 95%) compared with 60% (95% CI, 35% to 76%) in men. The efficacy of aspirin was not as consistent. The risk reduction with 75 mg of aspirin in the Atrial Fibrillation, Aspirin, Anticoagulation Study was 18% (95% CI, 60% to 58%), and with 325 mg of aspirin in the Stroke Prevention in Atrial Fibrillation Study the risk reduction was 44% (95% CI, 7% to 66%). When both studies were combined the risk reduction was 36% (95% CI, 4% to 57%). The annual rate of major hemorrhage (intracranial bleeding or a bleed requiring hospitalization or 2 units of blood) was 1.0% for the control group, 1.0% for the aspirin group, and 1.3% for the warfarin group. In these five randomized trials warfarin consistently decreased the risk of stroke in patients with atrial fibrillation (a 68% reduction in risk) with virtually no increase in the frequency of major bleeding. Patients with atrial fibrillation younger than 65 years without a history of hypertension, previous stroke or transient ischemic attack, or diabetes were at very low risk of stroke even when not treated. The efficacy of aspirin was less consistent. Further studies are needed to clarify the role of aspirin in atrial fibrillation.

Cost effectiveness of left atrial appendage closure with the Watchman device for atrial fibrillation patients with absolute contraindications to warfarin

PubMed Central

Reddy, Vivek Y.; Akehurst, Ronald L.; Armstrong, Shannon O.; Amorosi, Stacey L.; Brereton, Nic; Hertz, Deanna S.; Holmes, David R.

2016-01-01

Abstract Aims Atrial fibrillation (AF) patients with contraindications to oral anticoagulation have had few options for stroke prevention. Recently, a novel oral anticoagulant, apixaban, and percutaneous left atrial appendage closure (LAAC) have emerged as safe and effective therapies for stroke risk reduction in these patients. This analysis assessed the cost effectiveness of LAAC with the Watchman device relative to apixaban and aspirin therapy in patients with non-valvular AF and contraindications to warfarin therapy. Methods and results A cost-effectiveness model was constructed using data from three studies on stroke prevention in patients with contraindications: the ASAP study evaluating the Watchman device, the ACTIVE A trial of aspirin and clopidogrel, and the AVERROES trial evaluating apixaban. The cost-effectiveness analysis was conducted from a German healthcare payer perspective over a 20-year time horizon. Left atrial appendage closure yielded more quality-adjusted life years (QALYs) than aspirin and apixaban by 2 and 4 years, respectively. At 5 years, LAAC was cost effective compared with aspirin with an incremental cost-effectiveness ratio (ICER) of €16 971. Left atrial appendage closure was cost effective compared with apixaban at 7 years with an ICER of €9040. Left atrial appendage closure was cost saving and more effective than aspirin and apixaban at 8 years and remained so throughout the 20-year time horizon. Conclusions This analysis demonstrates that LAAC with the Watchman device is a cost-effective and cost-saving solution for stroke risk reduction in patients with non-valvular AF who are at risk for stroke but have contraindications to warfarin. PMID:26838691

Ischemic stroke classification and risk of embolism in patients with Chagas disease.

PubMed

Montanaro, Vinícius Viana Abreu; da Silva, Creuza Maria; de Viana Santos, Carla Verônica; Lima, Maria Inacia Ruas; Negrão, Edson Marcio; de Freitas, Gabriel R

2016-12-01

Ischemic stroke (IS) and Chagas disease are strongly related. Nevertheless, little attention has been paid to this association and its natural history. The current guidelines concerning the management and secondary prevention of IS are largely based on the incomplete information or extrapolation of knowledge from other stroke etiologies. We performed a retrospective study which compared stroke etiologies among a cohort of hospitalized patients with IS and Chagas disease. The Instituto de Pesquisa Evandro Chagas/Fundação Oswaldo Cruz (IPEC/FIOCRUZ) embolic score was also used to identify and evaluate the risk of embolism in this population. A total of 86 patients were included in the analysis. The mean age of the study population was 58 years, and 60 % were men. According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification, 45 % of the strokes were of undetermined etiology and 45 % of cardioembolic origin, while the Stop Stroke Study/Causative Classification System (SSS/CCS) TOAST indicated that 34 % were undetermined and 50 % cardioembolic (p < 0.01); 44 % of these patients were classified as having a high embolic risk according to the IPEC/FIOCRUZ score. Among the undetermined causes, 83.3 % fulfilled the criteria for embolic stroke of undetermined source (ESUS). The SSS/CCS TOAST etiological classification system was superior to the classical TOAST criteria in identifying a cardioembolic etiology in patients with ischemic stroke and Chagas disease. The IPEC/FIOCRUZ score did not correlate with the number of patients who were determined to have cardioembolic stroke etiologies. The current guidelines for stroke prevention should be reviewed in this population.

Thrombolytic Treatment for Ischaemic Stroke: Could the Crisis of Confidence Have Been Avoided by Better Analysis of Trial Data?

PubMed

Barer, David; Berge, Eivind

2017-02-01

In many countries, thrombolysis with intravenous alteplase has become a central part of acute stroke care in recent years, requiring radical restructuring of services. However, a significant minority of emergency and stroke physicians have always had serious doubts about the safety and efficacy of thrombolytic treatment, and in 2015 these prompted a major review of the licensing status of alteplase by the UK regulatory authorities. Subsequent dramatic headlines and media stories have called into question the integrity of researchers and clinicians and undermined public faith in medical research. How did this situation arise and what should be done to prevent a repetition as we enter the era of intra-arterial treatment for stroke?Early intravenous alteplase increases the chances both of good recovery and of severe haemorrhage, so the risk/benefit balance must be assessed for individual patients according to stroke severity. For older patients and those with bigger strokes, the 'good recovery' criterion is an inefficient way of assessing treatment effects since few achieve full independence and differences between levels of functional impairment are ignored. This waste of information can be reduced by applying different criteria for 'good' and 'poor' outcomes in different prognostic groups (as clinicians do intuitively), hence increasing the number of patients contributing useful data. Such 'three-way prognosis-based outcome' analysis of existing and future trials could greatly increase the amount of relevant evidence to guide clinical decisions for individual patients across the range of stroke severity.

Economic Evaluation of Apixaban for the Prevention of Stroke in Non-Valvular Atrial Fibrillation in the Netherlands

PubMed Central

Stevanović, Jelena; Pompen, Marjolein; Le, Hoa H.; Rozenbaum, Mark H.; Tieleman, Robert G.; Postma, Maarten J.

2014-01-01

Background Stroke prevention is the main goal of treating patients with atrial fibrillation (AF). Vitamin-K antagonists (VKAs) present an effective treatment in stroke prevention, however, the risk of bleeding and the requirement for regular coagulation monitoring are limiting their use. Apixaban is a novel oral anticoagulant associated with significantly lower hazard rates for stroke, major bleedings and treatment discontinuations, compared to VKAs. Objective To estimate the cost-effectiveness of apixaban compared to VKAs in non-valvular AF patients in the Netherlands. Methods Previously published lifetime Markov model using efficacy data from the ARISTOTLE and the AVERROES trial was modified to reflect the use of oral anticoagulants in the Netherlands. Dutch specific costs, baseline population stroke risk and coagulation monitoring levels were incorporated. Univariate, probabilistic sensitivity and scenario analyses on the impact of different coagulation monitoring levels were performed on the incremental cost-effectiveness ratio (ICER). Results Treatment with apixaban compared to VKAs resulted in an ICER of €10,576 per quality adjusted life year (QALY). Those findings correspond with lower number of strokes and bleedings associated with the use of apixaban compared to VKAs. Univariate sensitivity analyses revealed model sensitivity to the absolute stroke risk with apixaban and treatment discontinuations risks with apixaban and VKAs. The probability that apixaban is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 68%. Results of the scenario analyses on the impact of different coagulation monitoring levels were quite robust. Conclusions In patients with non-valvular AF, apixaban is likely to be a cost-effective alternative to VKAs in the Netherlands. PMID:25093723

Royal College of Physicians Intercollegiate Stroke Working Party evidence-based guidelines for the secondary prevention of stroke through nutritional or dietary modification.

PubMed

Hookway, C; Gomes, F; Weekes, C E

2015-04-01

Each year, 15 million people worldwide and 110,000 people in England have a stroke. Having a stroke increases the risk of having another. There are a number of additional known risk factors that can be modified by diet. The present study aimed to systematically review key nutrients and diets and their role in secondary prevention, as well as provide evidence-based guidelines for use in clinical practice. The work was conducted as part of the process to develop the 4th edition of the Royal College of Physicians' (RCP) National Clinical Guideline (NCG) for Stroke. Questions were generated by the research team, in consultation with the Virtual Stroke Group, an online professional interest group, and the RCP Intercollegiate Stroke Working Party Guideline Development Group. Nine questions covering several individual nutrients and diet combinations were defined and searches conducted up until 31 October 2011 using five electronic databases (Embase, Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library and Web of Science). All included studies were assessed for quality and risk of bias using van Tulder criteria for randomised controlled trials (RCTs) and Quality of Reporting of Meta-analyses (QUORUM) criteria for systematic reviews. Of 4287 abstracts were identified, 79 papers were reviewed and 29 systematic reviews and RCTs were included to provide evidence for the secondary prevention components of the guidelines. For each question, evidence statements, recommendations and practical considerations were developed. This systematic review process has resulted in the development of evidence-based guidelines for use in clinical practice and has identified areas for further research. © 2014 The British Dietetic Association Ltd.

Clinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent-protected angioplasty: a subanalysis of the SPACE study.

PubMed

Stingele, Robert; Berger, Jürgen; Alfke, Karsten; Eckstein, Hans-Henning; Fraedrich, Gustav; Allenberg, Jens; Hartmann, Marius; Ringleb, Peter A; Fiehler, Jens; Bruckmann, H; Hennerici, M; Jansen, O; Klein, G; Kunze, A; Marx, P; Niederkorn, K; Schmiedt, W; Solymosi, L; Zeumer, H; Hacke, W

2008-03-01

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are used to prevent ischaemic stroke in patients with stenosis of the internal carotid artery. Better knowledge of risk factors could improve assignment of patients to these procedures and reduce overall risk. We aimed to assess the risk of stroke or death associated with CEA and CAS in patients with different risk factors. We analysed data from 1196 patients randomised to CAS or CEA in the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE) trial. The primary outcome event was death or ipsilateral stroke (ischaemic or haemorrhagic) with symptoms that lasted more than 24 h between randomisation and 30 days after therapy. Six predefined variables were assessed as potential risk factors for this outcome: age, sex, type of qualifying event, side of intervention, degree of stenosis, and presence of high-grade contralateral stenosis or occlusion. The SPACE trial is registered at Current Controlled Trials, with the international standard randomised controlled trial number ISRCTN57874028. Risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0.001) but not in the CEA group (p=0.534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2.7% (8/293) in patients who were 68 years old or younger and 10.8% (34/314) in older patients. Other variables did not differ between the CEA and CAS groups. Of the predefined covariates, only age was significantly associated with the risk of stroke and death. The lower risk after CAS versus CEA in patients up to 68 years of age was not detectable in older patients. This finding should be interpreted with caution because of the drawbacks of post-hoc analyses.

Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).

PubMed

Halperin, Jonathan L; Hankey, Graeme J; Wojdyla, Daniel M; Piccini, Jonathan P; Lokhnygina, Yuliya; Patel, Manesh R; Breithardt, Günter; Singer, Daniel E; Becker, Richard C; Hacke, Werner; Paolini, John F; Nessel, Christopher C; Mahaffey, Kenneth W; Califf, Robert M; Fox, Keith A A

2014-07-08

Nonvalvular atrial fibrillation is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). This prespecified secondary analysis compares outcomes in older and younger patients. There were 6229 patients (44%) aged ≥75 years with atrial fibrillation and ≥2 stroke risk factors randomized to warfarin (target international normalized ratio=2.0-3.0) or rivaroxaban (20 mg daily; 15 mg if creatinine clearance <50 mL/min), double blind. The primary end point was stroke and systemic embolism by intention to treat. Over 10 866 patient-years, older participants had more primary events (2.57% versus 2.05%/100 patient-years; P=0.0068) and major bleeding (4.63% versus 2.74%/100 patient-years; P<0.0001). Stroke/systemic embolism rates were consistent among older (2.29% rivaroxaban versus 2.85% warfarin per 100 patient-years; hazard ratio=0.80; 95% confidence interval, 0.63-1.02) and younger patients (2.00% versus 2.10%/100 patient-years; hazard ratio=0.95; 95% confidence interval, 0.76-1.19; interaction P=0.313), as were major bleeding rates (≥75 years: 4.86% rivaroxaban versus 4.40% warfarin per 100 patient-years; hazard ratio=1.11; 95% confidence interval, 0.92-1.34; <75 years: 2.69% versus 2.79%/100 patient-years; hazard ratio=0.96; 95% confidence interval, 0.78-1.19; interaction P=0.336). Hemorrhagic stroke rates were similar in both age groups; there was no interaction between age and rivaroxaban response. Elderly patients had higher stroke and major bleeding rates than younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly. © 2014 American Heart Association, Inc.

Stroke subtyping for genetic association studies? A comparison of the CCS and TOAST classifications.

PubMed

Lanfranconi, Silvia; Markus, Hugh S

2013-12-01

A reliable and reproducible classification system of stroke subtype is essential for epidemiological and genetic studies. The Causative Classification of Stroke system is an evidence-based computerized algorithm with excellent inter-rater reliability. It has been suggested that, compared to the Trial of ORG 10172 in Acute Stroke Treatment classification, it increases the proportion of cases with defined subtype that may increase power in genetic association studies. We compared Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system classifications in a large cohort of well-phenotyped stroke patients. Six hundred ninety consecutively recruited patients with first-ever ischemic stroke were classified, using review of clinical data and original imaging, according to the Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system classifications. There was excellent agreement subtype assigned by between Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system (kappa = 0·85). The agreement was excellent for the major individual subtypes: large artery atherosclerosis kappa = 0·888, small-artery occlusion kappa = 0·869, cardiac embolism kappa = 0·89, and undetermined category kappa = 0·884. There was only moderate agreement (kappa = 0·41) for the subjects with at least two competing underlying mechanism. Thirty-five (5·8%) patients classified as undetermined by Trial of ORG 10172 in Acute Stroke Treatment were assigned to a definite subtype by Causative Classification of Stroke system. Thirty-two subjects assigned to a definite subtype by Trial of ORG 10172 in Acute Stroke Treatment were classified as undetermined by Causative Classification of Stroke system. There is excellent agreement between classification using Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke systems but no evidence that Causative Classification of Stroke system reduced the proportion of patients classified to undetermined subtypes. The excellent inter-rater reproducibility and web-based semiautomated nature make Causative Classification of Stroke system suitable for multicenter studies, but the benefit of reclassifying cases already classified using the Trial of ORG 10172 in Acute Stroke Treatment system on existing databases is likely to be small. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial

PubMed Central

Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Breithardt, Günter; Hankey, Graeme J.; Becker, Richard C.; Singer, Daniel E.; Halperin, Jonathan L.; Hacke, Werner; Nessel, Christopher C.; Berkowitz, Scott D.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

2015-01-01

Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Methods and results Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. PMID:25209598

Multicenter experience on eversion versus conventional carotid endarterectomy in symptomatic carotid artery stenosis: observations from the Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE-1) trial.

PubMed

Demirel, Serdar; Attigah, Nicolas; Bruijnen, Hans; Ringleb, Peter; Eckstein, Hans-Henning; Fraedrich, Gustav; Böckler, Dittmar

2012-07-01

Carotid endarterectomy (CEA) is beneficial in patients with symptomatic carotid artery stenosis. However, randomized trials have not provided evidence concerning the optimal CEA technique, conventional or eversion. The outcome of 563 patients within the surgical randomization arm of the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE-1) trial was analyzed by surgical technique subgroups: eversion endarterectomy versus conventional endarterectomy with patch angioplasty. The primary end point was ipsilateral stroke or death within 30 days after surgery. Secondary outcome events included perioperative adverse events and the 2-year risk of restenosis, stroke, and death. Both groups were similar in terms of demographic and other baseline clinical variables. Shunt frequency was higher in the conventional CEA group (65% versus 17%; P<0.0001). The risk of ipsilateral stroke or death within 30 days after surgery was significantly greater with eversion CEA (9% versus 3%; P=0.005). There were no statistically significant differences in the rate of perioperative secondary outcome events with the exception of a significantly higher risk of intraoperative ipsilateral stroke rate in the eversion CEA group (4% versus 0.3%; P=0.0035). The 2-year risk of ipsilateral stroke occurring after 30 days was significantly higher in the conventional CEA group (2.9% versus 0%; P=0.017). In patients with symptomatic carotid artery stenosis, conventional CEA appears to be associated with better periprocedural neurological outcome than eversion CEA. Eversion CEA, however, may be more effective for long-term prevention of ipsilateral stroke. These findings should be interpreted with caution noting the limitations of the post hoc, nonrandomized nature of the analysis.

Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention

PubMed Central

Wang, Juan; Chen, Dan; Li, Da-Bing; Yu, Xin; Shi, Guo-Bing

2016-01-01

Abstract Background: Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. Methods: A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. Results: For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P < 0.00001) and an 18% reduction in RR (RR 0.82, 95% CI [0.73, 0.93], P = 0.002) in the subgroup without renal transplant recipients and patients undergoing regular hemodialysis separately. For the fatal stroke incidences, intensive-dose statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. Conclusion: The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences. PMID:27684837

Can blood pressure be lowered safely in older adults with lacunar stroke? The Secondary Prevention of Small Subcortical Strokes study experience.

PubMed

White, Carole L; Szychowski, Jeff M; Pergola, Pablo E; Field, Thalia S; Talbert, Robert; Lau, Helena; Peri, Kalyani; Benavente, Oscar R

2015-04-01

To determine safety and tolerability of lowering blood pressure in older adults with lacunar stroke. Cohort study. The Secondary Prevention of Small Subcortical Strokes (SPS3) Trial, which compared the efficacy of two systolic blood pressure (SBP) targets (<130 mmHg and 130-149 mmHg) for secondary stroke prevention. Of 3,020 SPS3 participants, 494 aged 75 and older at baseline were used in these analyses. Rates of side effects related to lowering SBP and clinical outcomes, including stroke recurrence and vascular death, were examined. Older participants achieved SBP levels similar to those of younger participants (mean SBP of 125 mmHg and 137 mmHg in lower and higher SBP target groups, respectively). At least once during the approximately 3.5 years of follow-up, 21% reported dizziness, and 15% reported lightheadedness when standing; the only significant difference between the younger and older groups was unsteadiness when standing (23% vs 32% respectively, P < .001). There was no difference according to treatment group. In younger adults, recurrent stroke was less likely in the lower than the higher SBP group (hazard ratio (HR) = 0.77, 95% confidence interval (CI) = 0.59-1.01) but not in older participants (HR = 1.01, 95% CI = 0.59-1.73), although the interaction was not significant (P = .39). The lower SBP target was associated with a significant reduction in vascular death in older participants (HR = 0.42, 95% CI = 0.18-0.98), with a significant interaction between age and SBP group (P = .049). Except for unsteadiness when standing, there was no difference according to age in individuals with lacunar stroke with respect to side effects potentially related to lowering blood pressure. Although the lower SBP target was not associated with lower likelihood of recurrent stroke, these exploratory analyses suggested a possible benefit related to vascular death. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Telmisartan to prevent recurrent stroke and cardiovascular events.

PubMed

Yusuf, Salim; Diener, Hans-Christoph; Sacco, Ralph L; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-09-18

Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10). Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.) 2008 Massachusetts Medical Society

Severity of CIND and MCI predict incidence of dementia in an ischemic stroke cohort

PubMed Central

Narasimhalu, K; Ang, S; De Silva, D A.; Wong, M -C.; Chang, H -M.; Chia, K -S.; Auchus, A P.; Chen, C

2009-01-01

Background: The utility of poststroke cognitive status, namely dementia, cognitive impairment no dementia (CIND), mild cognitive impairment (MCI), and no cognitive impairment (NCI), in predicting dementia has been previously examined. However, no studies to date have compared the ability of subtypes of MCI and CIND to predict dementia in a poststroke population. Methods: A cohort of ischemic stroke patients underwent neuropsychological assessment annually for up to 5 years. Dementia was defined using the DSM-IV criteria. Univariate and multivariable Cox proportional regression was performed to determine the ability of MCI subtypes, CIND severity, and individual domains of impairment to predict dementia. Results: A total of 362 patients without dementia were followed up for a mean of 3.4 years (17% drop out), with 24 developing incident dementia. Older age, previous and recurrent stroke, and CIND and MCI subtypes were significant predictors of dementia. In multivariable analysis controlling for treatment allocation, patients who were older, had previous or recurrent stroke, and had either CIND moderate or multiple domain MCI with amnestic component were at elevated risk for dementia. In multivariable domain analysis, recurrent strokes, age, and previous strokes, verbal memory, and visual memory were significant predictors of dementia. Receiver operating characteristic curve analysis showed that CIND moderate (area under the curve: 0.893) and multiple domain MCI with amnestic component (area under the curve: 0.832) were significant predictors of conversion to dementia. All other classifications of cognitive impairment had areas under the curve less than 0.7. Conclusion: Stroke patients with cognitive impairment no dementia (CIND) moderate are at higher risk of developing dementia, while CIND mild patients are not at increased risk of developing dementia. GLOSSARY AD = Alzheimer disease; AUC = area under the curve; CI = confidence interval; CIND = cognitive impairment no dementia; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; ESPRIT = European Australasian Stroke Prevention in Reversible Ischemia Trial; ESPRIT-Cog = European Australasian Stroke Prevention in Reversible Ischemia Trial, cognitive substudy; HR = hazard ratio; LACI = lacunar infarct; MCI = mild cognitive impairment; mRS = modified Rankin scale; NCI = no cognitive impairment; OCSP = Oxfordshire Community Stroke Project; PACI = partial anterior circulation infarct; POCI = posterior circulation infarct; ROC = receiver operating curve; TACI = total anterior circulation infarct; VaD = vascular dementia; WAIS-R = Wechsler Adult Intelligence Scale–Revised; WMS-R = Wechsler Memory Scale–Revised. PMID:19949033

Cluster randomized trials utilizing primary care electronic health records: methodological issues in design, conduct, and analysis (eCRT Study)

PubMed Central

2014-01-01

Background There is growing interest in conducting clinical and cluster randomized trials through electronic health records. This paper reports on the methodological issues identified during the implementation of two cluster randomized trials using the electronic health records of the Clinical Practice Research Datalink (CPRD). Methods Two trials were completed in primary care: one aimed to reduce inappropriate antibiotic prescribing for acute respiratory infection; the other aimed to increase physician adherence with secondary prevention interventions after first stroke. The paper draws on documentary records and trial datasets to report on the methodological experience with respect to research ethics and research governance approval, general practice recruitment and allocation, sample size calculation and power, intervention implementation, and trial analysis. Results We obtained research governance approvals from more than 150 primary care organizations in England, Wales, and Scotland. There were 104 CPRD general practices recruited to the antibiotic trial and 106 to the stroke trial, with the target number of practices being recruited within six months. Interventions were installed into practice information systems remotely over the internet. The mean number of participants per practice was 5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures showed substantial correlations between the 12 months before, and after intervention, with coefficients ranging from 0.42 for diastolic blood pressure to 0.91 for proportion of consultations with antibiotics prescribed, defining practice and participant eligibility for analysis requires careful consideration. Conclusions Cluster randomized trials may be performed efficiently in large samples from UK general practices using the electronic health records of a primary care database. The geographical dispersal of trial sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans. Trial registration Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010). PMID:24919485

Effect of addition of clopidogrel to aspirin on subdural hematoma: meta-analysis of randomized clinical trials.

PubMed

Bakheet, Majid F; Pearce, Lesly A; Hart, Robert G

2015-06-01

Clopidogrel combined with aspirin is routinely prescribed after coronary artery stenting, in patients with acute coronary syndromes, and recently to prevent stroke in patients with acute minor ischemic stroke and TIA. Subdural hematomas are an important complication of antithrombotic treatment, but the risk associated with clopidogrel plus aspirin has not been previously defined. To quantify the risk of subdural hematoma associated with dual antiplatelet therapy with clopidogrel plus aspirin. Randomized clinical trials comparing clopidogrel plus aspirin with aspirin alone were identified by searching the Cochrane Central Register of Controlled Trials from 1990 to 2014, and restricted to those with more than 7 days of treatment. Two reviewers independently extracted data about subdural hematomas. Of 24 randomized trials testing clopidogrel added to aspirin, results for subdural hematoma were available for 11 trials, of which eight did not identify any subdural hematomas. The three trials reporting subdural hematomas were double-blind and included patients with recent lacunar stroke, acute coronary syndromes or atrial fibrillation with a total of 23,136 patients (mean age 66 years) and reported 39 subdural hematomas during a mean follow-up 2.1 years per patient. Clopidogrel plus aspirin was associated with a significantly increased risk of subdural hematoma compared with aspirin alone (risk ratio 2.0, 95% CI 1.0, 3.8; P = 0.04; fixed effects model; I2 for heterogeneity of 0%, P = 0.51). The average absolute incidence of subdural hematoma averaged 1.1 (95% CI 0.7,1.6) per 1000 patient - years among those assigned clopidogrel plus aspirin in 11 randomized trials. The absolute rate of subdural hematoma during dual antiplatelet therapy is low, averaging 1.1 per 1000 patient-years. Chronic treatment with clopidogrel plus aspirin significantly increases the risk of subdural hematoma compared with aspirin alone. © 2014 World Stroke Organization.

Decline in physical performance among women with a recent transient ischemic attack or ischemic stroke: opportunities for functional preservation a report of the Women's Estrogen Stroke Trial.

PubMed

Kernan, Walter N; Viscoli, Catherine M; Brass, Lawrence M; Gill, Thomas M; Sarrel, Philip M; Horwitz, Ralph I

2005-03-01

Physical performance for walking, reaching, turning, and other common tasks is a major determinant of functional independence after stroke. Current strategies to preserve physical performance focus on prevention of recurrent stroke. Loss of physical performance, however, may occur in the absence of recurrence. To examine this possibility, we measured change in physical performance, independent of subsequent stroke, among women with a recent ischemic stroke or transient ischemic attack (TIA). Among 664 postmenopausal women who participated in a clinical trial of estrogen therapy after stroke or TIA, we administered the Physical Performance Test (PPT) at baseline (mean 58 days from the cerebrovascular event) and annually. Women who died or had a stroke during follow-up were censored. Decline or improvement in physical performance was defined as a change in the PPT score from baseline of at least 3 points. Sustained decline or improvement was defined as 2 consecutive years during which the score had declined or improved, respectively, relative to the baseline score. With each year of follow-up, a smaller proportion of the cohort demonstrated improvement (16% in year 1, 6% in year 5) and a larger proportion demonstrated decline (15% in year 1, 35% in year 5). In an analysis restricted to 259 women with 3 years of follow-up, 46 (18%) experienced a nonsustained decline in physical performance, and 39 (15%) experienced a sustained decline. Decline in physical performance is common after an ischemic stroke or TIA even in the absence of a recurrent neurological event. Our findings suggest that specific interventions to maintain and improve physical performance may be important for reducing long-term disability.

Early Initiation of Anticoagulation with Direct Oral Anticoagulants in Patients after Transient Ischemic Attack or Ischemic Stroke.

PubMed

Macha, Kosmas; Volbers, Bastian; Bobinger, Tobias; Kurka, Natalia; Breuer, Lorenz; Huttner, Hagen B; Schwab, Stefan; Köhrmann, Martin

2016-09-01

Direct oral anticoagulants (DOACs) are increasingly used for secondary prevention of cardioembolic stroke. While DOACs are associated with a long-term reduced risk of intracranial hemorrhage compared to vitamin K antagonists, pivotal trials avoided the very early period after stroke and few data exist on early initiation of DOAC therapy post stroke. We retrospectively analyzed data from our prospective database of all consecutive transient ischemic attack (TIA) or ischemic stroke patients with atrial fibrillation treated with DOACs during hospital stay. As per our institutional treatment algorithm for patients with cardioembolic ischemia DOACs are started immediately in TIA and minor stroke (group 1), within days 3-5 in patients with infarcts affecting one third or less of the middle cerebral artery, the anterior cerebral artery, or the posterior cerebral artery territories (group 2) as well as in infratentorial stroke (group 3) and after 1-2 weeks in patients with large infarcts (>⅓MCA territory, group 4). We investigated baseline characteristics, time to initiation of DOAC therapy after symptom onset, and hemorrhagic complications. In 243 included patients, administration of DOAC was initiated 40.5 hours (interquartile range [IQR] 23.0-65.5) after stroke onset in group 1 (n = 41) and after 76.7 hours (IQR 48.0-134.0), 108.4 hours (IQR 67.3-176.4), and 161.8 hours (IQR 153.9-593.8) in groups 2-4 (n = 170, 28, and 4), respectively. Two cases of asymptomatic intracranial hemorrhage (.8%) and 1 case of symptomatic intracranial hemorrhage (.4%) were observed, both in group 2. No severe safety issues were observed in early initiation of DOACs for secondary prevention after acute stroke in our in-patient cohort. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Cluster randomized trials utilizing primary care electronic health records: methodological issues in design, conduct, and analysis (eCRT Study).

PubMed

Gulliford, Martin C; van Staa, Tjeerd P; McDermott, Lisa; McCann, Gerard; Charlton, Judith; Dregan, Alex

2014-06-11

There is growing interest in conducting clinical and cluster randomized trials through electronic health records. This paper reports on the methodological issues identified during the implementation of two cluster randomized trials using the electronic health records of the Clinical Practice Research Datalink (CPRD). Two trials were completed in primary care: one aimed to reduce inappropriate antibiotic prescribing for acute respiratory infection; the other aimed to increase physician adherence with secondary prevention interventions after first stroke. The paper draws on documentary records and trial datasets to report on the methodological experience with respect to research ethics and research governance approval, general practice recruitment and allocation, sample size calculation and power, intervention implementation, and trial analysis. We obtained research governance approvals from more than 150 primary care organizations in England, Wales, and Scotland. There were 104 CPRD general practices recruited to the antibiotic trial and 106 to the stroke trial, with the target number of practices being recruited within six months. Interventions were installed into practice information systems remotely over the internet. The mean number of participants per practice was 5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures showed substantial correlations between the 12 months before, and after intervention, with coefficients ranging from 0.42 for diastolic blood pressure to 0.91 for proportion of consultations with antibiotics prescribed, defining practice and participant eligibility for analysis requires careful consideration. Cluster randomized trials may be performed efficiently in large samples from UK general practices using the electronic health records of a primary care database. The geographical dispersal of trial sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans. Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010).

Sunlight exposure is important for preventing hip fractures in patients with Alzheimer's disease, Parkinson's disease, or stroke.

PubMed

Iwamoto, J; Takeda, T; Matsumoto, H

2012-04-01

Hypovitaminosis D as a result of malnutrition or sunlight deprivation, increased bone resorption, low bone mineral density (BMD), or an increased risk of falls may contribute to an increased risk of hip fractures in patients with neurological diseases, including Alzheimer's disease, Parkinson's disease, and stroke. The purpose of this study was to clarify the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with such neurological diseases. The English literature was searched using PubMed, and randomized controlled trials evaluating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer's disease, Parkinson's disease, and stroke were identified. The relative risk and the 95% confidence interval were calculated for individual randomized controlled trials, and a pooled data analysis (meta-analysis) was performed. Three randomized controlled trials were identified. Sunlight exposure improved hypovitaminosis D and increased the BMD. The relative risk (95% confidence interval) of hip fractures was 0.22 (0.05, 1.01) for Alzheimer's disease, 0.27 (0.08, 0.96) for Parkinson's disease, and 0.17 (0.02, 1.36) for stroke. The relative risk (95% confidence interval) calculated for the pooled data analysis was 0.23 (0.10, 0.56) (P = 0.0012), suggesting a significant risk reduction rate of 77%. The present meta-analysis added additional evidence indicating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer's disease, Parkinson's disease, and stroke. © 2011 John Wiley & Sons A/S.

Pathophysiology, treatment, and animal and cellular models of human ischemic stroke

PubMed Central

2011-01-01

Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to intensify efforts to ameliorate suffering and death from this common health catastrophe. This review aims to summarize both the present experimental and clinical state-of-the art, and to guide future research directions. PMID:21266064

Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable.

PubMed

Fisher, Marc; Albers, Gregory W; Donnan, Geoffrey A; Furlan, Anthony J; Grotta, James C; Kidwell, Chelsea S; Sacco, Ralph L; Wechsler, Lawrence R

2005-08-01

Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval. The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed. The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.

Role of Positive Airway Pressure Therapy for Obstructive Sleep Apnea in Patients With Stroke: A Randomized Controlled Trial

PubMed Central

Gupta, Anupama; Shukla, Garima; Afsar, Mohammed; Poornima, Shivani; Pandey, Ravindra M.; Goyal, Vinay; Srivastava, Achal; Vibha, Deepti; Behari, Madhuri

2018-01-01

Study Objectives: Obstructive sleep apnea (OSA) is an independent risk factor for stroke. The objective of this study was to assess the effect of continuous positive airway pressure (CPAP) treatment on prevention of new vascular events among patients with stroke and OSA. Methods: Consecutive conscious patients presenting with first imaging-confirmed arterial stroke were included, 6 weeks or more after ictus. All patients underwent clinical and polysomnography (PSG) testing. Patients with an apnea-hypopnea index (AHI) of > 15 events/h were randomized to posttitration nightly CPAP treatment and non-CPAP (received best medical treatment) groups. On follow-up at 3, 6, and 12 months from randomization, evaluation was carried out for any new vascular events as the primary outcome measure, and for clinical stroke outcomes (using the Barthel Index and modified Rankin scale) and neuropsychological parameters as the secondary outcome measures. Results: Among the 679 patients with stroke who were screened, 116 reported for PSG, 83 had AHI > 15 events/h, and 70 (34 in CPAP and 36 in non-CPAP) were randomized. Thirteen patients could not be randomized because of a lack of CPAP devices. Four patients crossed over from the CPAP to the non-CPAP group. Age (mean age 53.41 ± 9.85 in CPAP versus 52.69 ± 13.23 years in non-CPAP, P = .81) and sex distribution (24 males in CPAP versus 33 males in non-CPAP, P = .79) were similar in both groups. At 12-month follow-up, there was 1 vascular event (3.33%) in the CPAP group and 6 events (15%) in the non-CPAP group (P = .23). Modified Rankin scale score improvement by ≥ 1 at 12-month follow-up was found in significantly more patients in the CPAP group than in the non-CPAP group (53% versus 27%). Conclusions: These findings suggest significantly better stroke outcomes and statistically nonsignificant favorable outcomes in terms of recurrence of vascular events for patients with stroke and OSA who use CPAP treatment. Clinical Trial Registration: Registry: Clinical Trials Registry - India, CTRI Registration No: CTRI/2016/07.007104, Title: Sleep Disordered Breathing in stroke patients: Effect of treatment trial, URL: http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=8682&EncHid=&userName=sleep%20disordered%20breathing Citation: Gupta A, Shukla G, Afsar M, Poornima S, Pandey RM, Goyal V, Srivastava A, Vibha D, Behari M. Role of positive airway pressure therapy for obstructive sleep apnea in patients with stroke: a randomized controlled trial. J Clin Sleep Med. 2018;14(4):511–521. PMID:29609704

Maximizing Patient Recruitment and Retention in a Secondary Stroke Prevention Clinical Trial: Lessons Learned from the STAND FIRM Study.

PubMed

Thayabaranathan, Tharshanah; Cadilhac, Dominique A; Srikanth, Velandai K; Fitzgerald, Sharyn M; Evans, Roger G; Kim, Joosup; Gerraty, Richard P; Phan, Thanh G; Bladin, Christopher F; Nelson, Mark R; Frayne, Judith H; Thrift, Amanda G

2016-06-01

Recruitment and retention of patients in a clinical trial is important for generalizability and robustness of findings. We aimed to investigate features of a study design that were associated with recruitment and retention in a Phase II and Phase III trial of a secondary prevention program for stroke. Following informed consent in hospital, Phase II participants were randomized to intervention or usual care. Baseline clinical assessments were conducted at home approximately 3 months after discharge. In Phase III study, informed consent was obtained at home. We compared the characteristics of participants recruited and retained to 12 months for both phases. Interviews with study nurses were undertaken in order to ascertain their opinions of features of study design. Triangulation was used to identify the features of study design that nurses thought had improved recruitment and retention. All 24 eligible participants were recruited to the Phase II pilot study (100% recruitment), with 67% retention at 12 months. In Phase III study, 570 participants were recruited, and 93% of these participants had reached their 12-month assessment (n = 532) and were still participating. Consistent with the greater patient retention in Phase III study, nurses reported that patients' willingness to participate was greater when consent was obtained at home. Following a change in the consent process from hospital to home, more participants continued participation to 12 months. Pilot studies can provide important data to improve study design and better understand potential barriers to recruitment and retention. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Preventing Stroke Deaths

MedlinePlus

... Kit Read the MMWR Science Clips Preventing Stroke Deaths Progress Stalled Language: English (US) Español (Spanish) Recommend ... states. 80% of strokes are preventable. Problem Stroke deaths have stopped declining. Strokes are common and preventable. ...

Ximelagatran (AstraZeneca).

PubMed

Hopfner, Rob

2002-02-01

AstraZeneca (formerly Astra) is developing ximelagatran, an orally active thrombin inhibitor and prodrug of melagatran, for the potential prevention and treatment of venous thromboembolism (VTE) in hip and knee replacement, for prevention of stroke in atrialfibrillation (AF) and for post acute coronary syndrome. As of December 1999, the compound was undergoing phase III trials for the prevention of VTE [349551]; these were ongoing in December 2001. By December 2000, ximelagatran had entered phase III trials for the prevention of stroke in atrial fibrillation [395212]. In September 2000, the company expected global NDA filing for this indication to take place in the middle of 2001 [383469]; however, in December 2000 this was revised to the second half of 2002 [395212], and in March 2001, to the second quarter of 2003 [402040], [416882], [431673]. By December 2000, a phase II trial was underway of ximelagatran as a potential treatment following myocardial infarction [395237]. In December 2001, early phase clinical trials were ongoing for post acute coronary syndrome [431673]. By December 2001, EU and US filings for VTE prevention were anticipated in the third quarter of 2002 and the second quarter of 2003, respectively [3144721, [350050], [431673]. Exanta is the trade name for both melagatran and ximelagatran. In 1998, marketing of ximelagatran in the US was to be assigned to the Astra/Merek joint marketing venture, prior to the merger [276577]. In April 1999, ABN predicted sales of 4 pounds million in 2003 [328676], [394606]. In December 2000, Lehman Brothers estimated peak sales to be $1.4 billion [394606]. At the same time, ABN-AMRO predicted peak sales of more than $1 billion [395237]. In June 2000, Deutsche Bank predicted sales of $70 million in 2002, rising to $245 million in 2003 [374500]. In September 2000, Merrill Lynch predicted sales of 125 pounds million in 2002, rising to 625 pounds million in 2004 [383742]. In February 2001, Merrill Lynch estimated that peak sales would reach $924 million in 2005 [429697].

Cost-effectiveness of apixaban vs. current standard of care for stroke prevention in patients with atrial fibrillation

PubMed Central

Dorian, Paul; Kongnakorn, Thitima; Phatak, Hemant; Rublee, Dale A.; Kuznik, Andreas; Lanitis, Tereza; Liu, Larry Z.; Iloeje, Uchenna; Hernandez, Luis; Lip, Gregory Y.H.

2014-01-01

Aims Warfarin, a vitamin K antagonist (VKA), has been the standard of care for stroke prevention in patients with atrial fibrillation (AF). Aspirin is recommended for low-risk patients and those unsuitable for warfarin. Apixaban is an oral anticoagulant that has demonstrated better efficacy than warfarin and aspirin in the ARISTOTLE and AVERROES studies, respectively, and causes less bleeding than warfarin. We evaluated the potential cost-effectiveness of apixaban against warfarin and aspirin from the perspective of the UK payer perspective. Results and methods A lifetime Markov model was developed to evaluate the pharmacoeconomic impact of apixaban compared with warfarin and aspirin in VKA suitable and VKA unsuitable patients, respectively. Clinical events considered in the model include ischaemic stroke, haemorrhagic stroke, intracranial haemorrhage, other major bleed, clinically relevant non-major bleed, myocardial infarction, cardiovascular hospitalization and treatment discontinuations; data from the ARISTOTLE and AVERROES trials and published mortality rates and event-related utility rates were used in the model. Apixaban was projected to increase life expectancy and quality-adjusted life years (QALYs) compared with warfarin and aspirin. These gains were expected to be achieved at a drug acquisition-related cost increase over lifetime. The estimated incremental cost-effectiveness ratio was £11 909 and £7196 per QALY gained with apixaban compared with warfarin and aspirin, respectively. Sensitivity analyses indicated that results were robust to a wide range of inputs. Conclusions Based on randomized trial data, apixaban is a cost-effective alternative to warfarin and aspirin, in VKA suitable and VKA unsuitable patients with AF, respectively. PMID:24513791

Prevention of EP Migratory Contamination in a Cluster Randomized Trial to Increase tPA Use in Stroke (The INSTINCT Trial)

PubMed Central

Weston, Victoria C.; Meurer, William J.; Frederiksen, Shirley M.; Fox, Allison K.; Scott, Phillip A.

2016-01-01

Objectives Cluster randomized trials (CRTs) are increasingly utilized to evaluate quality improvement interventions aimed at healthcare providers. In trials testing emergency department interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating emergency departments would prevent migratory contamination in a CRT designed to increase ED delivery of tPA in stroke (The INSTINCT Trial). Methods INSTINCT was a prospective, cluster randomized, controlled trial. 24 Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as >10% of EPs affected. Non-adherence, total crossover (contamination + non-adherence), migration distance and characteristics were determined. Results 307 emergency physicians were identified at all sites. Overall, 7 (2.3%) changed study sites. 1 moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination) and 4 (1.3%) moved from control to intervention (non-adherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites. Conclusion The mobile nature of emergency physicians should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design. PMID:25440230

Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial.

PubMed

Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D; Hellkamp, Anne S; Piccini, Jonathan P; Stevens, Susanna R; Lokhnygina, Yuliya; Patel, Manesh R; Halperin, Jonathan L; Singer, Daniel E; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M

2014-12-14

We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55-1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75-1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05-1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94-1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Many patients with 'non-valvular atrial fibrillation' have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial

PubMed Central

Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D.; Hellkamp, Anne S.; Piccini, Jonathan P.; Stevens, Susanna R.; Lokhnygina, Yuliya; Patel, Manesh R.; Halperin, Jonathan L.; Singer, Daniel E.; Hankey, Graeme J.; Hacke, Werner; Becker, Richard C.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

2014-01-01

Aims We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. Methods and results ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55–1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75–1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05–1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94–1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Conclusions Many patients with ‘non-valvular atrial fibrillation’ have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. PMID:25148838

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

PubMed

Zanchetti, Alberto; Liu, Lisheng; Mancia, Giuseppe; Parati, Gianfranco; Grassi, Guido; Stramba-Badiale, Marco; Silani, Vincenzo; Bilo, Grzegorz; Corrao, Giovanni; Zambon, Antonella; Scotti, Lorenza; Zhang, Xinhua; Wang, HayYan; Zhang, Yuqing; Zhang, Xuezhong; Guan, Ting Rui; Berge, Eivind; Redon, Josep; Narkiewicz, Krzysztof; Dominiczak, Anna; Nilsson, Peter; Viigimaa, Margus; Laurent, Stéphane; Agabiti-Rosei, Enrico; Wu, Zhaosu; Zhu, Dingliang; Rodicio, José Luis; Ruilope, Luis Miguel; Martell-Claros, Nieves; Pinto, Fernando; Schmieder, Roland E; Burnier, Michel; Banach, Maciej; Cifkova, Renata; Farsang, Csaba; Konradi, Alexandra; Lazareva, Irina; Sirenko, Yuriy; Dorobantu, Maria; Postadzhiyan, Arman; Accetto, Rok; Jelakovic, Bojan; Lovic, Dragan; Manolis, Athanasios J; Stylianou, Philippos; Erdine, Serap; Dicker, Dror; Wei, Gangzhi; Xu, Chengbin; Xie, Hengge; Coca, Antonio; O'Brien, John; Ford, Gary

2014-09-01

The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125  mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8  mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.

Biomarkers and perfusion – training-induced changes after stroke (BAPTISe): protocol of an observational study accompanying a randomized controlled trial

PubMed Central

2013-01-01

Background Physical activity is believed to exert a beneficial effect on functional and cognitive rehabilitation of patients with stroke. Although studies have addressed the impact of physical exercise in cerebrovascular prevention and rehabilitation, the underlying mechanisms leading to improvement are poorly understood. Training-induced increase of cerebral perfusion is a possible mediating mechanism. Our exploratory study aims to investigate training-induced changes in blood biomarker levels and magnetic resonance imaging in patients with subacute ischemic stroke. Methods/design This biomarker-driven study uses an observational design to examine a subgroup of patients in the randomized, controlled PHYS-STROKE trial. In PHYS-STROKE, 215 patients with subacute stroke (hemorrhagic and ischemic) receive either 4 weeks of physical training (aerobic training, 5 times a week, for 50 minutes) or 4 weeks of relaxation sessions (5 times a week, for 50 minutes). A convenience sample of 100 of these patients with ischemic stroke will be included in BAPTISe and will receive magnetic resonance imaging (MRI) scans and an additional blood draw before and after the PHYS-STROKE intervention. Imaging scans will address parameters of cerebral perfusion, vessel size imaging, and microvessel density (the Q factor) to estimate the degree of neovascularization in the brain. Blood tests will determine several parameters of immunity, inflammation, endothelial function, and lipometabolism. Primary objective of this study is to evaluate differential changes in MRI and blood-derived biomarkers between groups. Other endpoints are next cerebrovascular events and functional status of the patient after the intervention and after 3 months assessed by functional scores, in particular walking speed and Barthel index (co-primary endpoints of PHYS-STROKE). Additionally, we will assess the association between functional outcomes and biomarkers including imaging results. For all endpoints we will compare changes between patients who received physical fitness training and patients who had relaxation sessions. Discussion This exploratory study will be the first to investigate the effects of physical fitness training in patients with ischemic stroke on MRI-based cerebral perfusion, pertinent blood biomarker levels, and functional outcome. The study may have an impact on current patient rehabilitation strategies and reveal important information about the roles of MRI and blood-derived biomarkers in ischemic stroke. Trial registration NCT01954797. PMID:24330706

Telerehabilitation to improve outcomes for people with stroke: study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background In New Zealand, around 45,000 people live with stroke and many studies have reported that benefits gained during initial rehabilitation are not sustained. Evidence indicates that participation in physical interventions can prevent the functional decline that frequently occurs after discharge from acute care facilities. However, on-going stroke services provision following discharge from acute care is often related to non-medical factors such as availability of resources and geographical location. Currently most people receive no treatment beyond three months post stroke. The study aims to determine if the Augmented Community Telerehabilitation Intervention (ACTIV) results in better physical function for people with stroke than usual care, as measured by the Stroke Impact Scale, physical subcomponent. Methods/design This study will use a multi-site, two-arm, assessor blinded, parallel randomised controlled trial design. People will be eligible if they have had their first ever stroke, are over 20 and have some physical impairment in either arm or leg, or both. Following discharge from formal physiotherapy services (inpatient, outpatient or community), participants will be randomised into ACTIV or usual care. ACTIV uses readily available technology, telephone and mobile phones, combined with face-to-face visits from a physiotherapist over a six-month period, to help people with stroke resume activities they enjoyed before the stroke. The impact of stroke on physical function and quality of life will be assessed, measures of cost will be collected and a discrete choice survey will be used to measure preferences for rehabilitation options. These outcomes will be collected at baseline, six months and 12 months. In-depth interviews will be used to explore the experiences of people participating in the intervention arm of the study. Discussion The lack of on-going rehabilitation for people with stroke diminishes the chance of their best possible outcome and may contribute to a functional decline following discharge from formal rehabilitation. Best practice guidelines recommend a prolonged period of rehabilitation, however this is expensive and therefore not undertaken in most publicly funded centres. An effective, cost-effective, and preference-sensitive therapy using basic technology to assist programme delivery may improve patient autonomy as they leave formal rehabilitation and return home. Trial registration ACTRN12612000464864 PMID:23216861

Intracranial Atherosclerotic Disease

PubMed Central

Khan, Maria; Naqvi, Imama; Bansari, Asha; Kamal, Ayeesha Kamran

2011-01-01

Intracranial atherosclerotic disease (ICAD) is the most common proximate mechanism of ischemic stroke worldwide. Approximately half of those affected are Asians. For diagnosis of ICAD, intra-arterial angiography is the gold standard to identify extent of stenosis. However, noninvasive techniques including transcranial ultrasound and MRA are now emerging as reliable modalities to exclude moderate to severe (50%–99%) stenosis. Little is known about measures for primary prevention of the disease. In terms of secondary prevention of stroke due to intracranial atherosclerotic stenosis, aspirin continues to be the preferred antiplatelet agent although clopidogrel along with aspirin has shown promise in the acute phase. Among Asians, cilostazol has shown a favorable effect on symptomatic stenosis and is of benefit in terms of fewer bleeds. Moreover, aggressive risk factor management alone and in combination with dual antiplatelets been shown to be most effective in this group of patients. Interventional trials on intracranial atherosclerotic stenosis have so far only been carried out among Caucasians and have not yielded consistent results. Since the Asian population is known to be preferentially effected, focused trials need to be performed to establish treatment modalities that are most effective in this population. PMID:21772967

Efficacy and safety of apixaban compared with aspirin in the elderly: a subgroup analysis from the AVERROES trial.

PubMed

Ng, Kuan H; Shestakovska, Olga; Connolly, Stuart J; Eikelboom, John W; Avezum, Alvaro; Diaz, Rafael; Lanas, Fernando; Yusuf, Salim; Hart, Robert G

2016-01-01

increasing age is associated with a higher prevalence of atrial fibrillation (AF), and higher risks of stroke and bleeding. We report the effects of apixaban versus acetylsalicylic acid (ASA) in older patients (≥75 years and ≥85 years) compared with younger patients with AF unsuitable for vitamin K antagonists. AVERROES (Apixaban Versus ASA to Prevent Stroke In AF Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) trial (n = 5,599) included 1,898 patients ≥75 years and 366 patients ≥85 years. We compared the baseline characteristics and effects of apixaban compared with aspirin on clinical outcomes by age. compared with aspirin, apixaban was more efficacious for preventing strokes and systemic embolism in patients ≥85 years (absolute rate [AR] 1%/year on apixaban versus 7.5%/year on aspirin; hazard ratio [HR] 0.14, 95% confidence interval [CI] 0.02-0.48) compared with younger patients (AR 1.7%/year on apixaban versus 3.4%/year on aspirin; HR 0.50, 95% CI 0.35-0.69) (P-value for interaction = 0.05). Major haemorrhage was higher in patients ≥85 years compared with younger patients but similar with apixaban versus aspirin in both young and older individuals (4.9%/year versus 1.0%/year on aspirin and 4.7%/year versus 1.2%/year on apixaban) with no significant treatment-by-age interaction (P-value = 0.65). older patients with AF are at particularly high risk of stroke if given aspirin and have substantially greater relative and absolute benefits from apixaban compared with younger patients with no greater risk of haemorrhage. ClinicalTrials.gov number: NCT00496769. URL: https://clinicaltrials.gov/ct2/show/NCT00496769. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reduction in early stroke risk in carotid stenosis with transient ischemic attack associated with statin treatment

PubMed Central

Merwick, Áine; Albers, Gregory W; Arsava, Ethem M; Ay, Hakan; Calvet, David; Coutts, Shelagh B; Cucchiara, Brett L; Demchuk, Andrew M; Giles, Matthew F; Mas, Jean-Louis; Olivot, Jean Marc; Purroy, Francisco; Rothwell, Peter M; Saver, Jeffrey L; Sharma, Vijay K; Tsivgoulis, Georgios; Kelly, Peter J

2013-01-01

Background and Purpose Statins reduce stroke risk when initiated months after TIA/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque-stabilisation. Few data exist regarding acute statin use in TIA. We aimed to determine if statin pre-treatment at TIA onset modified early stroke risk in carotid stenosis. Methods We analyzed data from 2770 TIA patients from 11 centres, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal DWI, medication pre-treatment, and early stroke were recorded. Results In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI] 5.7–11.1) compared with 2.7% [CI 2.0–3.4%] without stenosis (p<0.0001) (90-day risks 17.8% and 5.7% [p<0.0001]). Among carotid stenosis patients, non-procedural 7-day stroke risk was 3.8% [CI 1.2–9.7%] with statin treatment at TIA onset, compared to 13.2% [CI 8.5–19.8%] in those not statin pre-treated (p=0.01) (90-day risks 8.9% versus 20.8% [p=0.01]). Statin pre-treatment was associated with reduced stroke risk in carotid stenosis patients (OR for 90-day stroke 0.37, CI 0.17–0.82), but not non-stenosis patients (OR 1.3, CI 0.8–2.24) (p for interaction 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and DWI hyperintensity (adjusted p for interaction 0.054). Conclusion In acute symptomatic carotid stenosis, statin pre-treatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required. PMID:23908061

Improving Adherence to Secondary Stroke Prevention Strategies Through Motivational Interviewing: Randomized Controlled Trial.

PubMed

Barker-Collo, Suzanne; Krishnamurthi, Rita; Witt, Emma; Feigin, Valery; Jones, Amy; McPherson, Kathryn; Starkey, Nicola; Parag, Varsha; Jiang, Yannan; Barber, P Alan; Rush, Elaine; Bennett, Derrick; Aroll, Bruce

2015-12-01

Stroke recurrence rates are high (20%-25%) and have not declined over past 3 decades. This study tested effectiveness of motivational interviewing (MI) for reducing stroke recurrence, measured by improving adherence to recommended medication and lifestyle changes compared with usual care. Single-blind, prospective phase III randomized controlled trial of 386 people with stroke assigned to either MI treatment (4 sessions at 28 days, 3, 6, and 9 months post stroke) or usual care; with outcomes assessed at 28 days, 3, 6, 9, and 12 months post stroke. Primary outcomes were change in systolic blood pressure and low-density lipoprotein cholesterol levels as indicators of adherence at 12 months. Secondary outcomes included self-reported adherence, new stroke, or coronary heart disease events (both fatal and nonfatal); quality of life (Short Form-36); and mood (Hospital Anxiety and Depression Scale). MI did not significantly change measures of blood pressure (mean difference in change, -0.2.35 [95% confidence interval, -6.16 to 1.47]) or cholesterol (mean difference in change, -0.0.12 [95% confidence interval, -0.30 to 0.06]). However, it had positive effects on self-reported medication adherence at 6 months (1.979; 95% confidence interval, 0.98-3.98; P=0.0557) and 9 months (4.295; 95% confidence interval, 1.56-11.84; P=0.0049) post stroke. Improvement across other measures was also observed, but the differences between MI and usual care groups were not statistically significant. MI improved self-reported medication adherence. All other effects were nonsignificant, though in the direction of a treatment effect. Further study is required to determine whether MI leads to improvement in other important areas of functioning (eg, caregiver burden). URL: http://www.anzctr.org.au. Unique identifier: ACTRN-12610000715077. © 2015 American Heart Association, Inc.

Liver Cirrhosis in Patients With Atrial Fibrillation: Would Oral Anticoagulation Have a Net Clinical Benefit for Stroke Prevention?

PubMed

Kuo, Ling; Chao, Tze-Fan; Liu, Chia-Jen; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Lip, Gregory Y H; Chen, Shih-Ann

2017-06-23

Patients with liver cirrhosis have been excluded from randomized clinical trials of oral anticoagulation therapy for stroke prevention in atrial fibrillation. We hypothesized that patients with liver cirrhosis would have a positive net clinical benefit for oral anticoagulation when used for stroke prevention in atrial fibrillation. This study used the National Health Insurance Research Database in Taiwan. Among 289 559 atrial fibrillation patients aged ≥20 years, there were 10 336 with liver cirrhosis, and 9056 of them having a CHA 2 DS 2 -VASc score ≥2 were divided into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Patients with liver cirrhosis had a higher risk of ischemic stroke (hazard ratio=1.10, P =0.046) and intracranial hemorrhage (hazard ratio=1.20, P =0.043) compared with those without. Among patients with liver cirrhosis, patients taking antiplatelet therapy had a similar risk of ischemic stroke (hazard ratio=1.02, 95%CI=0.88-1.18) compared to those without antithrombotic therapies, but the risk was significantly lowered among warfarin users (hazard ratio=0.76, 95%CI=0.58-0.99). For intracranial hemorrhage, there were no significant differences between those untreated and those taking antiplatelet therapy or warfarin. The use of warfarin was associated with a positive net clinical benefit compared with being untreated or receiving only antiplatelet therapy. For atrial fibrillation patients with liver cirrhosis in the current analysis of an observational study, warfarin use was associated with a lower risk of ischemic stroke and a positive net clinical benefit compared with nontreatment, and thus, thromboprophylaxis should be considered for such patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Cost-effectiveness Analysis of Apixaban against Warfarin for Stroke Prevention in Patients with Nonvalvular Atrial Fibrillation in Japan.

PubMed

Kamae, Isao; Hashimoto, Yoichiro; Koretsune, Yukihiro; Tanahashi, Norio; Murata, Tatsunori; Phatak, Hemant; Liu, Larry Z; Tang, Ann C; Feng Wang, Peter; Okumura, Ken

2015-12-01

The aim of this study was to evaluate the cost-effectiveness of apixaban compared with to warfarin, current standard of care, for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan. A previously published lifetime Markov model was adapted to evaluate the cost-effectiveness of apixaban compared with warfarin in patients with NVAF in Japan. In the same model, the costs associated with each clinical event and background mortality were replaced with Japanese data. Whenever available, some of the utility parameters were derived from Japanese published literature. Lifetime horizon was selected to evaluate the value of the treatment benefit (stroke prevention) against potential risks (such as major bleedings) among patients with NVAF. Direct medical cost, long-term care cost, and quality-adjusted life years (QALYs) were calculated from the payers' perspective. Compared with warfarin, treatment with apixaban was estimated to increase life expectancy by 0.231 year or 0.240 QALYs while treatment cost increased by ¥511,692 (US $5117 at an exchange rate of US $1 = ¥100). The incremental cost-effectiveness ratio was ¥2,135,743 per QALY (US $21,357 per QALY). On the basis of the results of the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set at approximately ≥¥2,250,000 (US $22,500) per QALY, the probability of apixaban being cost-effective was ≥50%. Assuming a willingness-to-pay threshold of ¥5,000,000 (US $50,000) and ¥6,700,000 (US $67,000) in Japan, the probability of apixaban being cost-effective was 85% and 91%, respectively. Although most participants in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial used for the efficacy data of apixaban in the model were non-Japanese patients, the impact of the limitations on our results was considered small, and our results were deemed robust because of the additional effect in Japanese patients compared with that in the global population according to the subanalysis of Japanese patients in the trial. Therefore, based on an adaptation of a published Markov model, apixaban is a cost-effective alternative to warfarin in Japan for stroke prevention among patients with NVAF. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

PubMed

Hemphill, J Claude; Greenberg, Steven M; Anderson, Craig S; Becker, Kyra; Bendok, Bernard R; Cushman, Mary; Fung, Gordon L; Goldstein, Joshua N; Macdonald, R Loch; Mitchell, Pamela H; Scott, Phillip A; Selim, Magdy H; Woo, Daniel

2015-07-01

The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of spontaneous intracerebral hemorrhage. A formal literature search of PubMed was performed through the end of August 2013. The writing committee met by teleconference to discuss narrative text and recommendations. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee. Evidence-based guidelines are presented for the care of patients with acute intracerebral hemorrhage. Topics focused on diagnosis, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, outcome prediction, rehabilitation, secondary prevention, and future considerations. Results of new phase 3 trials were incorporated. Intracerebral hemorrhage remains a serious condition for which early aggressive care is warranted. These guidelines provide a framework for goal-directed treatment of the patient with intracerebral hemorrhage. © 2015 American Heart Association, Inc.

Case management reduces global vascular risk after stroke: secondary results from the The preventing recurrent vascular events and neurological worsening through intensive organized case-management randomized controlled trial.

PubMed

McAlister, Finlay A; Grover, Steven; Padwal, Raj S; Youngson, Erik; Fradette, Miriam; Thompson, Ann; Buck, Brian; Dean, Naeem; Tsuyuki, Ross T; Shuaib, Ashfaq; Majumdar, Sumit R

2014-12-01

Survivors of ischemic stroke/transient ischemic attack (TIA) are at high risk for other vascular events. We evaluated the impact of 2 types of case management (hard touch with pharmacist or soft touch with nurse) added to usual care on global vascular risk. This is a prespecified secondary analysis of a 6-month trial conducted in outpatients with recent stroke/TIA who received usual care and were randomized to additional monthly visits with either nurse case managers (who counseled patients, monitored risk factors, and communicated results to primary care physicians) or pharmacist case managers (who were also able to independently prescribe according to treatment algorithms). The Framingham Risk Score [FRS]) and the Cardiovascular Disease Life Expectancy Model (CDLEM) were used to estimate 10-year risk of any vascular event at baseline, 6 months (trial conclusion), and 12 months (6 months after last trial visit). Mean age of the 275 evaluable patients was 67.6 years. Both study arms were well balanced at baseline and exhibited reductions in absolute global vascular risk estimates at 6 months: median 4.8% (Interquartile range (IQR) 0.3%-11.3%) for the pharmacist arm versus 5.1% (IQR 1.9%-12.5%) for the nurse arm on the FRS (P = .44 between arms) and median 10.0% (0.1%-31.6%) versus 12.5% (2.1%-30.5%) on the CDLEM (P = .37). These reductions persisted at 12 months: median 6.4% (1.2%-11.6%) versus 5.5% (2.0%-12.0%) for the FRS (P = .83) and median 8.4% (0.1%-28.3%) versus 13.1% (1.6%-31.6%) on the CDLEM (P = .20). Case management by nonphysician providers is associated with improved global vascular risk in patients with recent stroke/TIA. Reductions achieved during the active phase of the trial persisted after trial conclusion. Copyright © 2014 Mosby, Inc. All rights reserved.

Critical early thrombolytic and endovascular reperfusion therapy for acute ischemic stroke victims: a call for adjunct neuroprotection.

PubMed

Lapchak, Paul A

2015-10-01

Today, there is an enormous amount of excitement in the field of stroke victim care due to the recent success of MR. CLEAN, SWIFT PRIME, ESCAPE, EXTEND-IA, and REVASCAT endovascular trials. Successful intravenous (IV) recombinant tissue plasminogen activator (rt-PA) clinical trials [i.e., National Institute of Neurological Disorders and Stroke (NINDS) rt-PA trial, Third European Cooperative Acute Stroke Study (ECASSIII), and Third International Stroke study (IST-3)] also need to be emphasized. In the recent endovascular and thrombolytic trials, there is statistically significant improvement using both the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Score (mRS) scale, but neither approach promotes complete recovery in patients enrolled within any particular NIHSS or mRS score tier. Absolute improvement (mRS 0-2 at 90 days) with endovascular therapy is 13.5-31 %, whereas thrombolytics alone also significantly improve patient functional independence, but to a lesser degree (NINDS rt-PA trial 13 %). This article has 3 main goals: (1) first to emphasize the utility and cost-effectiveness of rt-PA to treat stroke; (2) second to review the recent endovascular trials with respect to efficacy, safety, and cost-effectiveness as a stroke treatment; and (3) to further consider and evaluate strategies to develop novel neuroprotective drugs. A thesis will be put forth so that future stroke trials and therapy development can optimally promote recovery so that stroke victims can return to "normal" life.

Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin.

PubMed

Lanitis, T; Cotté, F E; Gaudin, A F; Kachaner, I; Kongnakorn, T; Durand-Zaleski, I

2014-08-01

To conduct an economic evaluation of the currently prescribed treatments for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) including warfarin, aspirin, and novel oral anticoagulants (NOACs) from a French payer perspective. A previously published Markov model was adapted in accordance to the new French guidelines of the Commission for Economic Evaluation and Public Health (CEESP), to adopt the recommended efficiency frontier approach. A cohort of patients with NVAF eligible for stroke preventive treatment was simulated over lifetime. Clinical events modeled included strokes, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds, and myocardial infarction. Efficacy and bleeding data for warfarin, apixaban, and aspirin were obtained from ARISTOTLE and AVERROES trials, whilst efficacy data for other NOACs were from published indirect comparisons. Acute medical costs were obtained from a dedicated analysis of the French national hospitalization database (PMSI). Long-term medical costs and utility data were derived from the literature. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model projections. Warfarin and apixaban were the two optimal treatment choices, as the other five treatment strategies including aspirin, dabigatran 110 mg, dabigatran in sequential dosages, dabigatran 150 mg, and rivaroxaban were strictly dominated on the efficiency frontier. Further, apixaban was a cost-effective alternative vs warfarin with an incremental cost of €2314 and an incremental quality-adjusted life year (QALY) of 0.189, corresponding to an incremental cost-effectiveness ratio (ICER) of €12,227/QALY. Apixaban may be the most economically efficient alternative to warfarin in NVAF patients eligible for stroke prevention in France. All other strategies were dominated, yielding apixaban as a less costly yet more effective treatment alternative. As formally requested by the CEESP, these results need to be verified in a French clinical setting using stroke reduction and bleeding safety observed in real-life patient cohorts using these anticoagulants.

Effects of clopidogrel added to aspirin in patients with recent lacunar stroke.

PubMed

Benavente, Oscar R; Hart, Robert G; McClure, Leslie A; Szychowski, Jeffrey M; Coffey, Christopher S; Pearce, Lesly A

2012-08-30

Lacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined. We conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage. The participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P=0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone). Among patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.).

Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial.

PubMed

1996-09-07

Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation (AF). However, this treatment carries a risk of bleeding and the need for frequent medical monitoring. We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism. 1044 patients with AF and with at least one thromboembolic risk factor (congestive heart failure or left ventricular fractional shortening < or = 25%, previous thromboembolism, systolic blood pressure of more than 160 mm Hg at study enrollment, or being a woman aged over 75 years) were randomly assigned either a combination of low-intensity, fixed-dose warfarin (international normalised ratio [INR] 1.2-1.5 for initial dose adjustment) and aspirin (325 mg/day) or adjusted-dose warfarin (INR 2.0-3.0). Drugs were given open-labelled. The mean INR during follow-up of patients taking combination therapy (n = 521) was 1.3, compared with 2.4 for those taking adjusted-dose warfarin (n = 523). During follow-up, 54% of INRs in patients taking combination therapy were 1.2-1.5 and 34% were less than 1.2. The trial was stopped after a mean, follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism (primary events) in patients given combination therapy (7.9% per year) was significantly higher than in those given adjusted-dose warfarin (1.9% per year) at an interim analysis (p < 0.0001), an absolute reduction of 6.0% per year (95% Cl 3.4, 8.6) by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p = 0.0007) and of primary event or vascular death (11.8% vs 6.4%, p = 0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups. Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-dose warfarin (target INR 2.0-3.0) importantly reduces stroke for high-risk patients.

Meta-Analysis of Effectiveness and Safety of Oral Anticoagulants in Atrial Fibrillation With Focus on Apixaban.

PubMed

Bai, Ying; Shi, Xu-Bo; Ma, Chang-Sheng; Lip, Gregory Y H

2017-11-01

We performed a meta-analysis of data on the effectiveness and safety of apixaban compared with other oral anticoagulants (warfarin or rivaroxaban or dabigatran or edoxaban) for stroke prevention in atrial fibrillation (AF) in different settings of randomized controlled trials, real-world studies, and radiofrequency ablation (RFA). Thirty studies were searched in PubMed, the Cochrane Library, and Clinicaltrials.gov databases reporting comparative effectiveness and safety of apixaban with warfarin (n = 23), rivaroxaban (n = 12), dabigatran (n = 13), or edoxaban (n = 2) for stroke prevention in AF. In real-world estimates, apixaban was similar to warfarin for the prevention of stroke or systematic thromboembolism (hazard ratio 0.93, 95% CI 0.71 to 1.14, I 2  = 82.9%, N = 7), and safer than warfarin in the risks of major bleeding (hazard ratio 0.62, 95% CI 0.54 to 0.70, I 2  = 18.7%, N = 9) in patients with AF. The risk of stroke or thromboembolism with apixaban was similar to rivaroxaban, dabigatran, and edoxaban in the settings of real-world studies and RFA. Major bleeding with apixaban was generally lower than rivaroxaban (relative risks 0.45, 95% CI 0.38 to 0.53, I 2  = 0%, N = 5) and similar to dabigatran in real-world studies (relative risks 1.44, 95% CI 0.33 to 6.30, I 2  = 97.7%, N = 5), but similar to rivaroxaban, dabigatran, and edoxaban in RFA. In conclusion, our meta-analysis provides a comprehensive estimate of the effectiveness and safety of apixaban compared with other oral anticoagulants (warfarin, rivaroxaban, dabigatran, and edoxaban) in patients with AF in different settings of randomized controlled trial, real-world studies, and RFA. Copyright © 2017 Elsevier Inc. All rights reserved.

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial.

PubMed

Saito, Yoshihiko; Okada, Sadanori; Ogawa, Hisao; Soejima, Hirofumi; Sakuma, Mio; Nakayama, Masafumi; Doi, Naofumi; Jinnouchi, Hideaki; Waki, Masako; Masuda, Izuru; Morimoto, Takeshi

2017-02-14

The long-term efficacy and safety of low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus are still inconclusive. The JPAD trial (Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes) was a randomized, open-label, standard care-controlled trial examining whether low-dose aspirin affected cardiovascular events in 2539 Japanese patients with type 2 diabetes mellitus and without preexisting cardiovascular disease. Patients were randomly allocated to receive aspirin (81 or 100 mg daily; aspirin group) or no aspirin (no-aspirin group) in the JPAD trial. After that trial ended in 2008, we followed up with the patients until 2015, with no attempt to change the previously assigned therapy. Primary end points were cardiovascular events, including sudden death, fatal or nonfatal coronary artery disease, fatal or nonfatal stroke, and peripheral vascular disease. For the safety analysis, hemorrhagic events, consisting of gastrointestinal bleeding, hemorrhagic stroke, and bleeding from any other sites, were also analyzed. The primary analysis was conducted for cardiovascular events among patients who retained their original allocation (a per-protocol cohort). Analyses on an intention-to-treat cohort were conducted for hemorrhagic events and statistical sensitivity. The median follow-up period was 10.3 years; 1621 patients (64%) were followed up throughout the study; and 2160 patients (85%) retained their original allocation. Low-dose aspirin did not reduce cardiovascular events in the per-protocol cohort (hazard ratio, 1.14; 95% confidence interval, 0.91-1.42). Multivariable Cox proportional hazard model adjusted for age, sex, glycemic control, kidney function, smoking status, hypertension, and dyslipidemia showed similar results (hazard ratio, 1.04; 95% confidence interval, 0.83-1.30), with no heterogeneity of efficacy in subgroup analyses stratified by each of these factors (all interaction P >0.05). Sensitivity analyses on the intention-to-treat cohort yielded consistent results (hazard ratio, 1.01; 95% confidence interval, 0.82-1.25). Gastrointestinal bleeding occurred in 25 patients (2%) in the aspirin group and 12 (0.9%) in the no-aspirin group ( P =0.03), and the incidence of hemorrhagic stroke was not different between groups. Low-dose aspirin did not affect the risk for cardiovascular events but increased risk for gastrointestinal bleeding in patients with type 2 diabetes mellitus in a primary prevention setting. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00110448. © 2016 American Heart Association, Inc.

Study protocol of the YOU CALL--WE CALL TRIAL: impact of a multimodal support intervention after a "mild" stroke.

PubMed

Rochette, Annie; Korner-Bitensky, Nicol; Bishop, Duane; Teasell, Robert; White, Carole; Bravo, Gina; Côté, Robert; Lachaine, Jean; Green, Teri; Lebrun, Louise-Hélène; Lanthier, Sylvain; Kapral, Moira; Wood-Dauphinee, Sharon

2010-01-06

More than 60% of new strokes each year are "mild" in severity and this proportion is expected to rise in the years to come. Within our current health care system those with "mild" stroke are typically discharged home within days, without further referral to health or rehabilitation services other than advice to see their family physician. Those with mild stroke often have limited access to support from health professionals with stroke-specific knowledge who would typically provide critical information on topics such as secondary stroke prevention, community reintegration, medication counselling and problem solving with regard to specific concerns that arise. Isolation and lack of knowledge may lead to a worsening of health problems including stroke recurrence and unnecessary and costly health care utilization.The purpose of this study is to assess the effectiveness, for individuals who experience a first "mild" stroke, of a sustainable, low cost, multimodal support intervention (comprising information, education and telephone support)--"WE CALL" compared to a passive intervention (providing the name and phone number of a resource person available if they feel the need to)--"YOU CALL", on two primary outcomes: unplanned-use of health services for negative events and quality of life. We will recruit 384 adults who meet inclusion criteria for a first mild stroke across six Canadian sites. Baseline measures will be taken within the first month after stroke onset. Participants will be stratified according to comorbidity level and randomised to one of two groups: YOU CALL or WE CALL. Both interventions will be offered over a six months period. Primary outcomes include unplanned use of heath services for negative event (frequency calendar) and quality of life (EQ-5D and Quality of Life Index). Secondary outcomes include participation level (LIFE-H), depression (Beck Depression Inventory II) and use of health services for health promotion or prevention (frequency calendar). Blind assessors will gather data at mid-intervention, end of intervention and one year follow up. If effective, this multimodal intervention could be delivered in both urban and rural environments. For example, existing infrastructure such as regional stroke centers and existing secondary stroke prevention clinics, make this intervention, if effective, deliverable and sustainable. ISRCTN95662526.

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

PubMed

Kernan, Walter N; Viscoli, Catherine M; Furie, Karen L; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Guarino, Peter D; Lovejoy, Anne M; Peduzzi, Peter N; Conwit, Robin; Brass, Lawrence M; Schwartz, Gregory G; Adams, Harold P; Berger, Leo; Carolei, Antonio; Clark, Wayne; Coull, Bruce; Ford, Gary A; Kleindorfer, Dawn; O'Leary, John R; Parsons, Mark W; Ringleb, Peter; Sen, Souvik; Spence, J David; Tanne, David; Wang, David; Winder, Toni R

2016-04-07

Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003). In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

Effect of prophylactic amiodarone on clinical and economic outcomes after cardiothoracic surgery: a meta-analysis.

PubMed

Gillespie, Effie L; Coleman, Craig I; Sander, Stephen; Kluger, Jeffrey; Gryskiewicz, Kristen A; White, C Michael

2005-09-01

Two previous meta-analyses of amiodarone for prevention of postoperative atrial fibrillation (POAF) after cardiothoracic surgery did not evaluate total hospital cost, concluded that data on stroke are incomplete, and did not evaluate the effect of clinical heterogeneity between trials. To conduct a meta-analysis examining amiodarone's prophylactic impact on cardiothoracic surgery POAF, length of stay (LOS), stroke, and total costs. Three reviewers conducted a systematic literature search of MEDLINE, EMBASE, CINAHL, and the Cochrane Library (1966-SEPTEMBER 2004). Studies were included if they met the following criteria: (1) randomized controlled trial versus placebo/routine treatment, (2) coronary artery bypass graft and/or valvular surgery, (3) Jadad score > or = 3, (4) reported data on incidence of POAF or stroke, LOS, or total costs, (5) used electrocardiographic/Holter monitoring, and (6) monitored subjects for > or = 2 days. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. Fifteen trials were identified, including 1512 and 1429 patients in the amiodarone and control groups, respectively. Amiodarone reduced POAF (OR 0.50; 95% CI 0.42 to 0.60) and decreased stroke (n = 8 studies), LOS (n = 10), and total costs (n = 6) (OR 0.47; 95% CI 0.23 to 0.96; -0.73 days, 95% CI -0.95 to -0.51; and -dollar 1619, 95% CI -3395 to 156, respectively). Surgery type, beta-blocker use, route of administration, use of a fixed-effects model, or exclusion of unblinded/unpublished studies did not affect the overall results. No statistical heterogeneity was observed for any endpoint evaluated (p > 0.22 for all comparisons). Prophylactic treatment with amiodarone decreases patients' risk of POAF and stroke while reducing LOS.

[New technology for prevention of embolic events in atrial fibrillation: a systematic review on percutaneous endovascular left atrial appendage closure].

PubMed

Danna, Paolo; Sagone, Antonio; Proietti, Riccardo; Arensi, Andrea; Viecca, Maurizio; Santangeli, Pasquale; Di Biase, Luigi; Natale, Andrea

2012-09-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The mortality rate of patients with AF is doubled as compared to non-fibrillating controls. The most relevant complication of AF is a major increase in the risk of stroke. The gold standard in reducing cerebrovascular events in AF is warfarin therapy, which is not free from contraindications and limitations. The left atrial appendage (LAA) is the main source of emboli causing stroke in AF. LAA closure is a seducing approach to stroke risk reduction in AF without anticoagulation. Since 1949, heart surgeons have performed LAA closure or amputation in patients with AF. Percutaneous endovascular LAA closure is a new, less invasive, technique to reach the goal. Several devices have been used to perform this intervention, and the results of published trials are encouraging in terms of effectiveness and relative safety of this attractive technique. In this review we examine the published trials and data on percutaneous LAA closure, with particular attention to the risks and benefits of this procedure.

A systematic review of the effectiveness of secondary prevention lifestyle interventions designed to change lifestyle behaviour following stroke.

PubMed

Lawrence, Maggie; Kerr, Susan; McVey, Ms Caroline; Godwin, Jon

Background Each year, approximately 15 million people worldwide have a stroke; of these, five million die and another five million are chronically disabled. Stroke recurs in approximately 25% of patients during the first five years post-stroke; recurrence may result in death, increased disability or institutionalisation. Modifiable risk factors for recurrent stroke have been identified, and may be addressed by means of behavioural health promotion interventions.Objectives This systematic review sought to establish the effectiveness of secondary prevention behavioural interventions, which address one or more modifiable lifestyle risk factors for recurrent stroke i.e. tobacco use, unhealthy diet, physical inactivity and excessive alcohol consumption. Types of participants The review included studies that had recruited adults (aged ≥18 years) who had had a stroke, minor stroke or transient ischaemic attack.Types of intervention The review considered studies that evaluated behavioural lifestyle interventions, designed to address the prevention of recurrent stroke.Types of outcomes Primary outcomes were concerned with lifestyle behaviour change i.e. tobacco use, diet, physical activity and alcohol consumption, and with change in physiological measures e.g. blood pressure, total cholesterol, and Body Mass Index. Secondary outcome measures included psychological outcomes, learning outcomes and incidence of stroke recurrence.Types of studies Experimental and non-experimental quantitative studies were considered.Search strategy In August 2009, we searched All EMB Reviews, AMED, ASSIA, British Nursing Index and Archive, CINAHL, Conference Proceedings Citation Index - Science, ProQuest dissertation and theses, EMBASE, MEDLINE, PsycINFO, and bibliographies of retrieved papers.Methodological quality and data extraction Two review authors independently assessed methodological quality using standardised critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument, and extracted data using a review-specific data extraction form.Data analysis Where possible, results from the review papers were pooled in statistical meta-analysis using bespoke software based on the system used by the Early Breast Cancer Trialists Collaborative Group. Where statistical pooling was not possible, findings are presented in narrative form.Results Three studies, two RCTs and one quasi-experimental study, involving 581 participants (baseline) were included in the review. Two models of service delivery were reported: shared care and nurse-led. Interventions were delivered to groups or in one-to-one consultations.Meta-analyses of the pooled lifestyle data favoured the interventions (2p=0.02; Note: here and throughout, 2p represents the two-tailed probability). In terms of physiological outcomes, the pooled data favoured the interventions (2p=0.05), particularly those aiming to reduce blood pressure and cholesterol levels. The pooled secondary outcomes, including perceived health status and stroke knowledge favoured the interventions (2p<0.00001), however, the test for heterogeneity was also highly significant.Conclusions Stroke secondary prevention lifestyle interventions are effective in terms of affecting positive change in relation to lifestyle behaviours, physiological and secondary outcomes. However, there was insufficient evidence to determine the effect of intervention on incidence of stroke recurrence.Implications for practice Clinicians should implement stroke secondary prevention interventions which address lifestyle behaviours, physiological factors, psychological outcomes and stroke knowledge.Implications for research Further large-scale, well-designed trials are needed to determine the factors that impact on the effectiveness of secondary prevention interventions.

Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial.

PubMed

Powers, William J; Clarke, William R; Grubb, Robert L; Videen, Tom O; Adams, Harold P; Derdeyn, Colin P

2011-11-09

Patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) and hemodynamic cerebral ischemia are at high risk for subsequent stroke when treated medically. To test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia. Parallel-group, randomized, open-label, blinded-adjudication clinical treatment trial conducted from 2002 to 2010. Forty-nine clinical centers and 18 positron emission tomography (PET) centers in the United States and Canada. The majority were academic medical centers. Patients with arteriographically confirmed AICAO causing hemispheric symptoms within 120 days and hemodynamic cerebral ischemia identified by ipsilateral increased oxygen extraction fraction measured by PET. Of 195 patients who were randomized, 97 were randomized to receive surgery and 98 to no surgery. Follow-up for the primary end point until occurrence, 2 years, or termination of trial was 99% complete. No participant withdrew because of adverse events. Anastomosis of superficial temporal artery branch to a middle cerebral artery cortical branch for the surgical group. Antithrombotic therapy and risk factor intervention were recommended for all participants. For all participants who were assigned to surgery and received surgery, the combination of (1) all stroke and death from surgery through 30 days after surgery and (2) ipsilateral ischemic stroke within 2 years of randomization. For the nonsurgical group and participants assigned to surgery who did not receive surgery, the combination of (1) all stroke and death from randomization to randomization plus 30 days and (2) ipsilateral ischemic stroke within 2 years of randomization. The trial was terminated early for futility. Two-year rates for the primary end point were 21.0% (95% CI, 12.8% to 29.2%; 20 events) for the surgical group and 22.7% (95% CI, 13.9% to 31.6%; 20 events) for the nonsurgical group (P = .78, Z test), a difference of 1.7% (95% CI, -10.4% to 13.8%). Thirty-day rates for ipsilateral ischemic stroke were 14.4% (14/97) in the surgical group and 2.0% (2/98) in the nonsurgical group, a difference of 12.4% (95% CI, 4.9% to 19.9%). Among participants with recently symptomatic AICAO and hemodynamic cerebral ischemia, EC-IC bypass surgery plus medical therapy compared with medical therapy alone did not reduce the risk of recurrent ipsilateral ischemic stroke at 2 years. clinicaltrials.gov Identifier: NCT00029146.

Independent and Joint Effect of Brachial-Ankle Pulse Wave Velocity and Blood Pressure Control on Incident Stroke in Hypertensive Adults.

PubMed

Song, Yun; Xu, Benjamin; Xu, Richard; Tung, Renee; Frank, Eric; Tromble, Wayne; Fu, Tong; Zhang, Weiyi; Yu, Tao; Zhang, Chunyan; Fan, Fangfang; Zhang, Yan; Li, Jianping; Bao, Huihui; Cheng, Xiaoshu; Qin, Xianhui; Tang, Genfu; Chen, Yundai; Yang, Tianlun; Sun, Ningling; Li, Xiaoying; Zhao, Lianyou; Hou, Fan Fan; Ge, Junbo; Dong, Qiang; Wang, Binyan; Xu, Xiping; Huo, Yong

2016-07-01

Pulse wave velocity (PWV) has been shown to influence the effects of antihypertensive drugs in the prevention of cardiovascular diseases. Data are limited on whether PWV is an independent predictor of stroke above and beyond hypertension control. This longitudinal analysis examined the independent and joint effect of brachial-ankle PWV (baPWV) with hypertension control on the risk of first stroke. This report included 3310 hypertensive adults, a subset of the China Stroke Primary Prevention Trial (CSPPT) with baseline measurements for baPWV. During a median follow-up of 4.5 years, 111 participants developed first stroke. The risk of stroke was higher among participants with baPWV in the highest quartile than among those in the lower quartiles (6.3% versus 2.4%; hazard ratio, 1.66; 95% confidence interval, 1.06-2.60). Similarly, the participants with inadequate hypertension control had a higher risk of stroke than those with adequate control (5.1% versus 1.8%; hazard ratio, 2.32; 95% confidence interval, 1.49-3.61). When baPWV and hypertension control were examined jointly, participants in the highest baPWV quartile and with inadequate hypertension control had the highest risk of stroke compared with their counterparts (7.5% versus 1.3%; hazard ratio, 3.57; 95% confidence interval, 1.88-6.77). There was a significant and independent effect of high baPWV on stroke as shown among participants with adequate hypertension control (4.2% versus 1.3%; hazard ratio, 2.29, 95% confidence interval, 1.09-4.81). In summary, among hypertensive patients, baPWV and hypertension control were found to independently and jointly affect the risk of first stroke. Participants with high baPWV and inadequate hypertension control had the highest risk of stroke compared with other groups. © 2016 American Heart Association, Inc.

Effect of lipid-lowering therapy on the progression of intracranial arterial stenosis.

PubMed

Tan, Teng-Yeow; Kuo, Yeh-Lin; Lin, Wei-Che; Chen, Ting-Yao

2009-02-01

Intracranial arterial stenosis (IAS) is a severe disease with a high recurrent stroke rate even under the best medical treatment. Statins have been demonstrated to prevent stroke and to slow or halt atherosclerosis progression. This study was performed to observe the effect of atorvastatin on the progression of IAS, explore the factors associated with atherosclerosis regression and the recurrent rate of stroke. A hospital-base observation study enrolled 40 stroke patients with middle cerebral artery (MCA) or/and basilar artery (BA) stenosis. All participants had hyperlipidemia and were given atorvastatin 40 mg per day for at least six months. IAS was assessed by magnetic resonance angiogram (MRA) at the time of enrollment and then at least six months later. The primary outcome was the progression of IAS. All patients were also given antiplatelet agents for stroke prevention. At the end of the study, 23 (58 %), 15 (38 %) and 2 (4 %) patients had regressed, stationary and progressed IAS, respectively. Females were likely to have regressed IAS. The recurrent stroke rate was 18 %. Among the 54 stenotic vessels, 29 (54 %) vessels were assessed as improvement in stenosis. Compared with other studies, more regressed, stationary IAS and less progressed IAS were found in our study. Female gender was likely to have regressed IAS after statin treatment. Further clinical outcome trials are required to assess the effects of such therapy on morbidity and mortality in this particular group of patients.

Progress in reducing the burden of stroke.

PubMed

Chalmers, J; Chapman, N

2001-12-01

1. The burden of stroke worldwide is growing rapidly, driven by an ageing population and by the rapid rate of urbanization and industrialization in the developing world. There are approximately 5 million fatal and 15 million non-fatal strokes each year and over 50 million survivors of stroke alive, worldwide, today. 2. The most important determinant of stroke risk is blood pressure, with a strong, continuous relationship between the level of the systolic and diastolic pressures and the risk of initial and recurrent stroke, in both Western and Asian populations. 3. Randomized clinical trials have clearly demonstrated that blood pressure lowering reduces the risk of initial stroke by 35-40% in hypertensive patients; but, until recently, there was no conclusive evidence that blood pressure lowering was effective in the secondary prevention of stroke. 4. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) has provided definitive evidence that blood pressure lowering in patients with previous stroke or transient ischaemic attack (TIA) reduces the incidence of secondary stroke by 28%, of major vascular events by 26% and of major coronary events by 26%. These reductions were all magnified by approximately 50% in a subgroup of patients in whom the angiotensin-converting enzyme inhibitor perindopril was routinely combined with the diuretic indapamide. 5. Successful global implementation of a treatment with perindopril and indapamide in patients with a history of stroke or TIA would markedly reduce the burden of stroke and could avert between 0.5 and one million strokes each year, worldwide.

78 FR 42529 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-16

... Stroke Special Emphasis Panel Stroke Trials Network NCCC SEP. Date: August 15, 2013. Time: 8:00 a.m. to...: National Institute of Neurological Disorders and Stroke Special Emphasis Panel Stroke Trial Network Sites... Related to Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences, National...

Vinpocetine for acute ischaemic stroke.

PubMed

Bereczki, D; Fekete, I

2008-01-23

Vasoactive and neuroprotective drugs such as vinpocetine are used to treat stroke in some countries. To assess the effect of vinpocetine in acute ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched February 2007), MEDLINE (1966 to February 2007) and Scopus (1960 to February 2007). We also searched the Internet Stroke Center Stroke Trials Registry, Google Scholar, the science-specific search engine Scirus and Wanfang Data, the leading information provider in China. We contacted researchers in the field and four pharmaceutical companies that manufacture vinpocetine. Searches were complete to February 2007. Unconfounded randomised trials of vinpocetine compared with placebo, or any other reference treatment, in people with acute ischaemic stroke. We included trials if treatment started no later than 14 days after stroke onset. Two review authors independently applied the inclusion criteria. One review author extracted the data, which was then checked by the second review author. We assessed trial quality. The primary outcome measure was death or dependency. We included two trials, involving a total of 70 participants. Data for 63 participants were reported in the two trials combined. The rate of death or dependency did not differ between the treatment and placebo groups at one and three months. The 95% confidence intervals for the outcome measures were wide and included the possibility of both significant benefit and significant harm. No adverse effects were reported. There is not enough evidence to evaluate the effect of vinpocetine on survival or dependency in patients with acute ischaemic stroke.

Blood pressure measurement reliability among different racial-ethnic groups in a stroke prevention study.

PubMed

Estol, Conrado J; Bath, Philip M W; Gorelick, Philip B; Cotton, Daniel; Martin, Renee H; Weber, Michael A; Dahlof, Bjorn

2014-10-01

High blood pressure (BP) is commonly not diagnosed, and patients do not achieve target values when treated. Among 20,000 patients encompassing most races-ethnicities, we evaluated BP measurements and treatment response in a stroke prevention trial. Our goal was to identify BP measurement differences between clinical trial and patient determinations and among the racial-ethnic groups. A total of 20,332 patients with ischemic stroke were randomized to receive antiplatelet treatment and 80 mg of telmisartan versus placebo. BP measurements were obtained at the first clinic visit and then 1 and 3 months later and every 6 months thereafter. One week after the first clinic visit, patients were requested to report a BP measurement obtained elsewhere. Measurements at the trial clinics were obtained with the same electronic device. Statistical analysis was used to detect significant differences. The mean patient age was 66 years; 36% were women, and race-ethnicity comprised 58% Whites, 33% Asian, 4.9% Hispanic, and 4% Black. Overall, 74% of patients were hypertensive. BP varied between the race-ethnicity groups, being highest in Hispanics (145/85) and lowest in Blacks (144/82). BP at visits clinic 1, nonclinic 1A, and clinic 2 were, respectively, 144/84, 137/80, and 139/81 mmHg, with the difference between visits 1-2 and visit 1A being significant. BPs were normal in 42% of the cases at visit 1A, and of these, only 44% were normal at visit 1 and 57.6% were normal on visit 2. Similar findings were noted for all race-ethnicity groups. BP values varied among race-ethnicities and showed differences between clinic and patient measurements. This finding questions the reliability of self-reported BP and has implications for BP management in daily clinical practice.

Efficacy and safety of rivaroxaban compared with warfarin in patients with carotid artery disease and nonvalvular atrial fibrillation: Insights from the ROCKET AF trial.

PubMed

Kochar, Ajar; Hellkamp, Anne S; Lokhnygina, Yuliya; Jones, W Schuyler; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Singer, Daniel E; Piccini, Jonathan P; Patel, Manesh R

2018-01-01

Atrial fibrillation (AF) increases risk of stroke 5-fold. Carotid artery disease (CD) also augments the risk of stroke, yet there are limited data about the interplay of these 2 diseases and clinical outcomes in patients with comorbid AF and CD. Among patients with both AF and CD, use of rivaroxaban when compared with warfarin is associated with a lower risk of stroke. This post hoc analysis from ROCKET AF aimed to determine absolute rates of stroke/systemic embolism (SE) and bleeding, and the efficacy and safety of rivaroxaban compared with warfarin in patients with AF and CD (defined as history of carotid occlusive disease or carotid revascularization [endarterectomy and/or stenting]). A total of 593 (4.2%) patients had CD at enrollment. Patients with and without CD had similar rates of stroke or SE (adjusted hazard ratio [HR]: 0.99, 95% confidence interval [CI]: 0.66-1.48, P = 0.96), and there was no difference in major or nonmajor clinically relevant bleeding (adjusted HR: 1.04, 95% CI: 0.88-1.24, P = 0.62). The efficacy of rivaroxaban compared with warfarin for the prevention of stroke/SE was not statistically significant in patients with vs those without CD (interaction P = 0.25). The safety of rivaroxaban vs warfarin for major or nonmajor clinically relevant bleeding was similar in patients with and without CD (interaction P = 0.64). Patients with CD in ROCKET AF had similar risk of stroke/SE compared with patients without CD. Additionally, there was no interaction between CD and the treatment effect of rivaroxaban or warfarin for stroke prevention or safety endpoints. © 2018 Wiley Periodicals, Inc.

Percutaneous left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation and contraindication for anticoagulation.

PubMed

Grosset-Janin, D; Barth, E; Bertrand, B; Detante, O

2015-05-01

Stroke, as the third cause of death in developed countries, is a public health issue. Atrial fibrillation is an important cause of ischemic stroke and its prevention is efficient with oral anticoagulation. However, oral anticoagulation can be contraindicated because of hemorrhagic risk related to these treatments. Percutaneous left atrial appendage occlusion is a new alternative of oral anticoagulation for patients with atrial fibrillation and high risk of cardio-embolic stroke but contraindicated for oral anticoagulation. We describe in this paper the procedure of left atrial appendage occlusion with the Amplatzer cardiac plug device, used in our center in Grenoble university hospital, for the first three patients who have been treated with this device. These three patients (one man and two women) have all atrial fibrillation with neurological complication of this arrhythmia, as ischemic stroke. Oral anticoagulation is indicated to prevent another ischemic stroke. However, they all have a high risk of cerebral bleeding for different reasons (cavernomatosis, history of intracerebral hemorrhage and aneurysm of the polygon of Willis). Consequently, they have a high risk of cardio-embolic complication but contraindication for oral anticoagulation. They have been treated by left atrial appendage occlusion with Amplatzer cardiac plug device by percutaneous and trans-septal access. Then, they have been followed by neurologist and cardiologist, with clinical and paraclinical evaluation by echocardiography. Our three first patients have been successfully implanted, without periprocedural complication. No latest adverse event was observed, and particularly no cardiac or neurologic adverse event. The technique of left atrial appendage occlusion is a very interesting and promising technique for ischemic stroke prevention in patient with high risk of cardio-embolic complication because of atrial fibrillation, but high risk of bleeding and contraindication for oral anticoagulation. Because of frequency of both atrial fibrillation and contraindication for oral anticoagulation, occlusion of the left atrial appendage should become an interesting alternative for many patients. However, it remains an invasive procedure and efficacy and indications need to be evaluated in further clinical trials. Risk/benefit ratio must be carefully assessed and compared to that of the new anticoagulant drugs. Copyright © 2015. Published by Elsevier Masson SAS.

A strategic plan to accelerate development of acute stroke treatments.

PubMed

Marler, John R

2012-09-01

In order to reenergize acute stroke research and accelerate the development of new treatments, we need to transform the usual design and conduct of clinical trials to test for small but significant improvements in effectiveness, and treat patients as soon as possible after stroke onset when treatment effects are most detectable. This requires trials that include thousands of acute stroke patients. A plan to make these trials possible is proposed. There are four components: (1) free access to the electronic medical record; (2) a large stroke emergency network and clinical trial coordinating center connected in real time to hundreds of emergency departments; (3) a clinical trial technology development center; and (4) strategic leadership to raise funds, motivate clinicians to participate, and interact with politicians, insurers, legislators, and other national and international organizations working to advance the quality of stroke care. © 2012 New York Academy of Sciences.

Iron deficiency, ischaemic strokes, and right-to-left shunts: From pulmonary arteriovenous malformations to patent foramen ovale?

PubMed Central

Shovlin, Claire L.

2014-01-01

Summary Has the recent identification of iron deficiency as a risk factor for ischaemic stroke in patients with pulmonary arteriovenous malformations (AVMs) unmasked a new paradigm for stroke/infarct pathogenesis? This commentary reviews evidence that spans associations between iron deficiency and ischaemic strokes, iron deficiency enhancement of platelet aggregation in response to serotonin/5HT, settings in which plasma 5HT is elevated, and clinical trial confirmation that 5HT receptor antagonists prevent ischaemic stroke. The critical leap which directs attention away from atherothrombotic events at the neurovascular wall is that ischaemic strokes due to pulmonary AVMs are attributable to compromised pulmonary capillary bed filtration of venous blood. Right-to-left shunting is continuous through pulmonary AVMs, but also occurs intermittently in approximately 30% of the general population with intracardiac shunts such as patent foramen ovale (PFO). The testable hypothesis presented is that paradoxical embolism of venous platelet-based aggregates may constitute part of the causal chain between iron deficiency and ischaemic stroke, not only in the rare disease state of pulmonary AVMs, but also in major subgroups of the general population. PMID:25343129

Characteristics and Outcomes of Very Elderly Enrolled in a Prehospital Stroke Research Study.

PubMed

Sanossian, Nerses; Apibunyopas, Kathleen C; Liebeskind, David S; Starkman, Sidney; Burgos, Adrian M; Conwit, Robin; Eckstein, Marc; Pratt, Frank; Stratton, Sam; Hamilton, Scott; Saver, Jeffrey L

2016-11-01

Greater numbers of individuals aged ≥80 years enjoy a high quality of life, yet historically stroke trials have excluded this population. We aimed to describe a population of very elderly successfully enrolled into an acute stroke trial and compare their characteristics and outcomes with the younger cohort. We analyzed consecutive patients enrolled <2 hours of symptom onset in a prehospital stroke treatment trial, the FAST-MAG clinical trial (Field Administration of Stroke Therapy-Magnesium). We gathered demographic, treatment, and outcome data for nonelderly (<80 years old), very elderly (≥80 years old), and extreme elderly (≥90 years old). We describe key differences in the population of elderly and the impact of their inclusion on the clinical trial. Of 1700 participants in FAST-MAG, there were 1210 nonelderly, 490 very elderly, and 60 extreme elderly subjects. Very elderly stroke patients successfully enrolled in a research study were more likely to be women, white, and have an ischemic mechanism rather than an intracerebral hemorrhage. Although the very elderly had generally poorer outcomes, 4 in 10 were functionally independent at 90 days. Inclusion of the very elderly population in acute stroke clinical trials would both significantly increase study participation and generalizability of future acute stroke clinical trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332. © 2016 American Heart Association, Inc.

Prevention of emergency physician migratory contamination in a cluster randomized trial to increase tissue plasminogen activator use in stroke (the INSTINCT trial).

PubMed

Weston, Victoria C; Meurer, William J; Frederiksen, Shirley M; Fox, Allison K; Scott, Phillip A

2014-12-01

Cluster randomized trials (CRTs) are increasingly used to evaluate quality improvement interventions aimed at health care providers. In trials testing emergency department (ED) interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating EDs would prevent migratory contamination in a CRT designed to increase ED delivery of tissue plasminogen activator (tPA) in stroke (the INSTINCT trial). INSTINCT was a prospective, cluster randomized, controlled trial. Twenty-four Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as greater than 10% of EPs affected. Nonadherence, total crossover (contamination+nonadherence), migration distance, and characteristics were determined. Three hundred seven EPs were identified at all sites. Overall, 7 (2.3%) changed study sites. One moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination); and 4 (1.3%) moved from control to intervention (nonadherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites. The mobile nature of EPs should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design. Copyright © 2014 Elsevier Inc. All rights reserved.

[Effectiveness of endarterectomy for symptomatic stenosis of the internal carotid artery; more risk factors important than only the severity of the stenosis].

PubMed

Klijn, C J M; Hoefnagels, W A J; Brouwers, P J A M; Luijckx, G J; Moll, F L; Kappelle, L J

2007-12-15

Carotid endarterectomy prevents ischaemic stroke in patients who have suffered either a transient ischaemic attack (TIA) or a non-disabling ischaemic stroke and are also diagnosed with severe stenosis of the internal carotid artery (ICA). In order to prevent the occurrence ofa single stroke, 6 patients with a symptomatic 70 to 99% ICA stenosis will have to be operated upon. A meta-analysis of individual patient data from 3 randomised trials shows that the decision whether to advise endarterectomy to an individual patient should not be based solely on the degree of the ICA stenosis, but also on the time interval between symptoms and surgery, the type and severity of symptoms and the plaque morphology. In general, endarterectomy is more effective in men than in women, it is very effective in the elderly, and it is even more effective when performed within two weeks of the symptoms occurring. A decision scheme has been set up enabling one to predict the absolute risk of an ipsilateral stroke in the next 5 years in individual patients who have symptomatic ICA stenosis. This is based on 5 factors: sex, age, the most severe symptom in the last 6 months (stroke, TIA, or ischaemic retinopathy), the number of weeks since the last incident and the morphological characteristics of the plaque.

A community-based educational intervention to improve antithrombotic drug use in atrial fibrillation.

PubMed

Jackson, Shane L; Peterson, Gregory M; Vial, Janet H

2004-11-01

Despite evidence that antithrombotics are effective in reducing the risk of stroke in atrial fibrillation (AF), they remain underused. To perform a controlled trial of a comprehensive educational program promoting the rational prescribing of antithrombotics for stroke prevention in AF. The intervention was conducted in Southern Tasmania, Australia, using Northern Tasmania as a control area. General practitioners were sent locally produced guidelines on stroke risk stratification and antithrombotic drug use in AF, which were followed by academic detailing visits. Outcomes were measured using evaluation feedback from the general practitioners, and drug utilization data were provided by a series of patients presenting to the hospital with an admission diagnosis of AF and dispensing of antithrombotic therapy under the Australian Pharmaceutical Benefits Scheme. During the educational intervention, 272 guidelines were mailed and, subsequently, 162 general practitioners were visited and the guidelines discussed. Hospital admission data before and after the intervention revealed a significant increase in the use of warfarin in patients at high risk of stroke (33% vs 46% of eligible patients; p < 0.05). Analysis of prescription data for warfarin also indicated that the increase in use of warfarin within the intervention region was significantly greater than for the control region (p < 0.001). The educational program described here led to a significant increase in the prescribing of warfarin for stroke prevention in patients with AF.

Cost-effectiveness of apixaban vs. current standard of care for stroke prevention in patients with atrial fibrillation.

PubMed

Dorian, Paul; Kongnakorn, Thitima; Phatak, Hemant; Rublee, Dale A; Kuznik, Andreas; Lanitis, Tereza; Liu, Larry Z; Iloeje, Uchenna; Hernandez, Luis; Lip, Gregory Y H

2014-07-21

Warfarin, a vitamin K antagonist (VKA), has been the standard of care for stroke prevention in patients with atrial fibrillation (AF). Aspirin is recommended for low-risk patients and those unsuitable for warfarin. Apixaban is an oral anticoagulant that has demonstrated better efficacy than warfarin and aspirin in the ARISTOTLE and AVERROES studies, respectively, and causes less bleeding than warfarin. We evaluated the potential cost-effectiveness of apixaban against warfarin and aspirin from the perspective of the UK payer perspective. A lifetime Markov model was developed to evaluate the pharmacoeconomic impact of apixaban compared with warfarin and aspirin in VKA suitable and VKA unsuitable patients, respectively. Clinical events considered in the model include ischaemic stroke, haemorrhagic stroke, intracranial haemorrhage, other major bleed, clinically relevant non-major bleed, myocardial infarction, cardiovascular hospitalization and treatment discontinuations; data from the ARISTOTLE and AVERROES trials and published mortality rates and event-related utility rates were used in the model. Apixaban was projected to increase life expectancy and quality-adjusted life years (QALYs) compared with warfarin and aspirin. These gains were expected to be achieved at a drug acquisition-related cost increase over lifetime. The estimated incremental cost-effectiveness ratio was £11 909 and £7196 per QALY gained with apixaban compared with warfarin and aspirin, respectively. Sensitivity analyses indicated that results were robust to a wide range of inputs. Based on randomized trial data, apixaban is a cost-effective alternative to warfarin and aspirin, in VKA suitable and VKA unsuitable patients with AF, respectively. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

An updated systematic review and meta-analysis of early outcomes after left atrial appendage occlusion.

PubMed

Yerasi, Charan; Lazkani, Mohamad; Kolluru, Prathik; Miryala, Varun; Kim, Jae; Moole, Harsha; Sawant, Abhishek C; Morris, Michael; Pershad, Ashish

2018-04-01

Left atrial appendage occlusion (LAAO) is a promising intervention for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Early outcomes following LAAO have been published in many studies with variable results. This updated meta-analysis aims to provide a summary of the early outcomes of LAAO. Medline/Pubmed, Ovid Journals, Clinical trials, Abstract meetings, Cochrane databases were searched from January 1st, 1999 to November 30th, 2016. This meta-analysis included 49 studies involving 12 415 patients. The median age was 73.5 years (IQR 72-75 years) and 43% were males. Hypertension and diabetes were present in 36% and 15% of the population, respectively. There was a prior history of stroke and congestive heart failure in 14% and 18% of the population, respectively. The median CHADS 2 score was 2.9 (IQR 2.6-3.3) and the median HASBLED score was 3.3 (IQR 3-4). LAAO implantation was successful in 96.3% of patients (95.40-97.08, I 2  = 76.1%). The pooled proportion of all-cause mortality was 0.28% (0.19-0.38, I 2  = 0%). The pooled proportion of all-cause stroke was 0.31% (0.22-0.42, I 2  = 9.4%), major bleeding requiring transfusion was 1.71% (1.13-2.41, I 2  = 73.2%), and pericardial effusion was 3.25% (2.46-4.14, I 2  = 79%). Sub analysis of randomized clinical trials comparing LAAO devices to warfarin showed lower mortality (P = 0.03) with similar bleeding risk (P = 0.20) with LAAO. This meta-analysis concludes that LAAO occlusion is a safe and effective stroke prevention strategy in patients with NVAF. © 2018, Wiley Periodicals, Inc.

Novel anticoagulants for stroke prevention in atrial fibrillation: a systematic review of cost-effectiveness models.

PubMed

Limone, Brendan L; Baker, William L; Kluger, Jeffrey; Coleman, Craig I

2013-01-01

To conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF). We searched Medline, Embase, NHSEED and HTA databases and the Tuft's Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation) models of newer agents for SPAF. Eighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%), European (39%) and Canadian (17%) perspectives. Models typically assumed patients between 65-73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110 mg (n = 4)/150 mg (n = 2); rivaroxaban (n = 1)) vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547-$86,000 for dabigatran 150 mg, $20,713-$150,000 for dabigatran 110 mg, $4,084-$21,466 for sequentially-dosed dabigatran and $23,065-$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400-$25,059) vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results. Cost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent.

Novel Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Systematic Review of Cost-Effectiveness Models

PubMed Central

Limone, Brendan L.; Baker, William L.; Kluger, Jeffrey; Coleman, Craig I.

2013-01-01

Objective To conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF). Patients and Methods We searched Medline, Embase, NHSEED and HTA databases and the Tuft’s Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation) models of newer agents for SPAF. Results Eighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%), European (39%) and Canadian (17%) perspectives. Models typically assumed patients between 65–73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110 mg (n = 4)/150 mg (n = 2); rivaroxaban (n = 1)) vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547–$86,000 for dabigatran 150 mg, $20,713–$150,000 for dabigatran 110 mg, $4,084–$21,466 for sequentially-dosed dabigatran and $23,065–$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400–$25,059) vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results. Conclusions Cost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent. PMID:23626785

Achieved Blood Pressure and Outcomes in the Secondary Prevention of Small Subcortical Strokes Trial.

PubMed

Odden, Michelle C; McClure, Leslie A; Sawaya, B Peter; White, Carole L; Peralta, Carmen A; Field, Thalia S; Hart, Robert G; Benavente, Oscar R; Pergola, Pablo E

2016-01-01

Studies suggest a J-shaped association between blood pressure and cardiovascular events in the setting of intensive systolic blood pressure control; whether there is a similar association with stroke remains less well established. The Secondary Prevention of Small Subcortical Strokes was a randomized trial to evaluate higher (130-149 mm Hg) versus lower (<130 mm Hg) systolic blood pressure targets in participants with recent lacunar infarcts. We evaluated the association of mean achieved blood pressure, 6 months after randomization, and recurrent stroke, major vascular events, and all-cause mortality. After a mean follow up of 3.7 years, there was a J-shaped association between achieved blood pressure and outcomes; the lowest risk was at ≈124 and 67 mm Hg systolic and diastolic blood pressure, respectively. For example, above a systolic blood pressure of 124 mm Hg, 1 standard deviation higher (11.1 mm Hg) was associated with increased mortality (adjusted hazard ratio: 1.9; 95% confidence interval: 1.4, 2.7), whereas below this level, this relationship was inverted (0.29; 0.10, 0.79), P<0.001 for interaction. Above a diastolic blood pressure of 67 mm Hg, a 1 standard deviation higher (8.2 mm Hg) was associated with an increased risk of stroke (2.2; 1.4, 3.6), whereas below this level, the association was in the opposite direction (0.34; 0.13, 0.89), P=0.02 for interaction. The lowest risk of all events occurred at a nadir of ≈120 to 128 mm Hg systolic blood pressure and 65 to 70 mm Hg diastolic blood pressure. Future studies should evaluate the impact of excessive blood pressure reduction, especially in older populations with preexisting vascular disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306. © 2015 American Heart Association, Inc.

Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

PubMed

Westenbrink, B Daan; Alings, Marco; Granger, Christopher B; Alexander, John H; Lopes, Renato D; Hylek, Elaine M; Thomas, Laine; Wojdyla, Daniel M; Hanna, Michael; Keltai, Matyas; Steg, P Gabriel; De Caterina, Raffaele; Wallentin, Lars; van Gilst, Wiek H

2017-03-01

Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes. We performed a post hoc analysis of the ARISTOTLE trial, which included >18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin <13.0 in men and <12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality. Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS 2 and HAS-BLED scores, and were more likely to have experienced previous bleeding events. Anemia was associated with major bleeding (adjusted hazard ratio [HR], 1.92; 95% CI, 1.62-2.28; P<.0001) and all-cause mortality (adjusted HR, 1.68; 95% CI, 1.46-1.93; P<.0001) but not stroke or systemic embolism (adjusted HR, 0.92; 95% CI, 0.70-1.21). The benefits of apixaban compared with warfarin on the rates of stroke, mortality, and bleeding events were consistent in patients with and without anemia. Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A Multicomponent Behavioral Intervention to Reduce Stroke Risk Factor Behaviors: The Stroke Health and Risk Education Cluster-Randomized Controlled Trial.

PubMed

Brown, Devin L; Conley, Kathleen M; Sánchez, Brisa N; Resnicow, Kenneth; Cowdery, Joan E; Sais, Emma; Murphy, Jillian; Skolarus, Lesli E; Lisabeth, Lynda D; Morgenstern, Lewis B

2015-10-01

The Stroke Health and Risk Education Project was a cluster-randomized, faith-based, culturally sensitive, theory-based multicomponent behavioral intervention trial to reduce key stroke risk factor behaviors in Hispanics/Latinos and European Americans. Ten Catholic churches were randomized to intervention or control group. The intervention group received a 1-year multicomponent intervention (with poor adherence) that included self-help materials, tailored newsletters, and motivational interviewing counseling calls. Multilevel modeling, accounting for clustering within subject pairs and parishes, was used to test treatment differences in the average change since baseline (ascertained at 6 and 12 months) in dietary sodium, fruit and vegetable intake, and physical activity, measured using standardized questionnaires. A priori, the trial was considered successful if any one of the 3 outcomes was significant at the 0.05/3 level. Of 801 subjects who consented, 760 completed baseline data assessments, and of these, 86% completed at least one outcome assessment. The median age was 53 years; 84% subjects were Hispanic/Latino; and 64% subjects were women. The intervention group had a greater increase in fruit and vegetable intake than the control group (0.25 cups per day [95% confidence interval: 0.08, 0.42], P=0.002), a greater decrease in sodium intake (-123.17 mg/d [-194.76, -51.59], P=0.04), but no difference in change in moderate- or greater-intensity physical activity (-27 metabolic equivalent-minutes per week [-526, 471], P=0.56). This multicomponent behavioral intervention targeting stroke risk factors in predominantly Hispanics/Latinos was effective in increasing fruit and vegetable intake, reaching its primary end point. The intervention also seemed to lower sodium intake. Church-based health promotions can be successful in primary stroke prevention efforts. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01378780. © 2015 American Heart Association, Inc.

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial.

PubMed

Steinberg, Benjamin A; Hellkamp, Anne S; Lokhnygina, Yuliya; Patel, Manesh R; Breithardt, Günter; Hankey, Graeme J; Becker, Richard C; Singer, Daniel E; Halperin, Jonathan L; Hacke, Werner; Nessel, Christopher C; Berkowitz, Scott D; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Piccini, Jonathan P

2015-02-01

Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Shared decision making for stroke prevention in atrial fibrillation: study protocol for a randomized controlled trial.

PubMed

Kunneman, Marleen; Branda, Megan E; Noseworthy, Peter A; Linzer, Mark; Burnett, Bruce; Dick, Sara; Spencer-Bonilla, Gabriela; Fernandez, Cara A; Gorr, Haeshik; Wambua, Mike; Keune, Shelly; Zeballos-Palacios, Claudia; Hargraves, Ian; Shah, Nilay D; Montori, Victor M

2017-09-29

Nonvalvular atrial fibrillation (AF) is a common ongoing health problem that places patients at risk of stroke. Whether and how a patient addresses this risk depends on each patient's goals, context, and values. Consequently, leading cardiovascular societies recommend using shared decision making (SDM) to individualize antithrombotic treatment in patients with AF. The aim of this study is to assess the extent to which the ANTICOAGULATION CHOICE conversation tool promotes high-quality SDM and influences anticoagulation uptake and adherence in patients with AF at risk of strokes. This study protocol describes a multicenter, encounter-level, randomized trial to assess the effect of using the ANTICOAGULATION CHOICE conversation tool in the clinical encounter, compared to usual care. The participating centers include an academic hospital system, a suburban community group practice, and an urban safety net hospital, all in Minnesota, USA. Patients with ongoing nonvalvular AF at risk of strokes (CHA 2 DS 2 -VASc score ≥ 1 in men, or ≥ 2 in women) will be eligible for participation. We aim to include 999 patients and their clinicians. The primary outcome is the quality of SDM as perceived by participants, and as assessed by a post-encounter survey that ascertains (a) knowledge transfer, (b) concordance of the decision made, (c) quality of communication, and (d) satisfaction with the decision-making process. Recordings of encounters will be reviewed to assess the extent of patient involvement and how participants use the tool (fidelity). Anticoagulant use, choice of agent, and adherence will be drawn from patients' medical and pharmacy records. Strokes and bleeding events will be drawn from patient records. This study will provide a valid and precise measure of the effect of the ANTICOAGULATION CHOICE conversation tool on SDM quality and processes, and on the treatment choices and adherence to therapy among AF patients at risk of stroke. ClinicalTrials.gov, NCT02905032 . Registered on 9 September 2016.

Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Morrow, David A; Murphy, Sabina A; Kuder, Julia F; Deenadayalu, Naveen; Jarolim, Petr; Betcher, Joshua; Shi, Minggao; Brown, Karen; Patel, Indravadan; Mercuri, Michele; Antman, Elliott M

2015-06-06

New oral anticoagulants for stroke prevention in atrial fibrillation were developed to be given in fixed doses without the need for the routine monitoring that has hindered usage and acceptance of vitamin K antagonists. A concern has emerged, however, that measurement of drug concentration or anticoagulant activity might be needed to prevent excess drug concentrations, which significantly increase bleeding risk. In the ENGAGE AF-TIMI 48 trial, higher-dose and lower-dose edoxaban were compared with warfarin in patients with atrial fibrillation. Each regimen incorporated a 50% dose reduction in patients with clinical features known to increase edoxaban drug exposure. We aim to assess whether adjustment of edoxaban dose in this trial prevented excess drug concentration and the risk of bleeding events. We analysed data from the randomised, double-blind ENGAGE AF-TIMI 48 trial. We correlated edoxaban dose, plasma concentration, and anti-Factor Xa (FXa) activity and compared efficacy and safety outcomes with warfarin stratified by dose reduction status. Patients with atrial fibrillation and at moderate to high risk of stroke were randomly assigned in a 1:1:1 ratio to receive warfarin, dose adjusted to an international normalised ratio of 2·0-3·0, higher-dose edoxaban (60 mg once daily), or lower-dose edoxaban (30 mg once daily). Randomisation was done with use of a central, 24 h, interactive, computerised response system. International normalised ratio was measured using an encrypted point-of-care device. To maintain masking, sham international normalised ratio values were generated for patients assigned to edoxaban. Edoxaban (or placebo-edoxaban in warfarin group) doses were halved at randomisation or during the trial if patients had creatinine clearance 30-50 mL/min, bodyweight 60 kg or less, or concomitant medication with potent P-glycoprotein interaction. Efficacy outcomes included the primary endpoint of all-cause stroke or systemic embolism, ischaemic stroke, and all-cause mortality. Safety outcomes included the primary safety endpoint of major bleeding, fatal bleeding, intracranial haemorrhage, and gastrointestinal bleeding. This trial is registered with ClinicalTrials.gov, number NCT00781391. Between Nov 19, 2008 and Nov 22, 2010, 21 105 patients were recruited. Patients who met clinical criteria for dose reduction at randomisation (n=5356) had higher rates of stroke, bleeding, and death compared with those who did not have a dose reduction (n=15 749). Edoxaban dose ranged from 15 mg to 60 mg, resulting in a two-fold to three fold gradient of mean trough drug exposure (16·0-48·5 ng/mL in 6780 patients with data available) and mean trough anti-FXa activity (0·35-0·85 IU/mL in 2865 patients). Dose reduction decreased mean exposure by 29% (from 48·5 ng/mL [SD 45·8] to 34·6 ng/mL [30·9]) and 35% (from 24·5 ng/mL [22·7] to 16·0 ng/mL [14·5]) and mean anti-FXa activity by 25% (from 0·85 IU/mL [0·76] to 0·64 IU/mL [0·54]) and 20% (from 0·44 IU/mL [0·37] to 0·35 IU/mL [0·28]) in the higher-dose and lower-dose regimens, respectively. Despite the lower anti-FXa activity, dose reduction preserved the efficacy of edoxaban compared with warfarin (stroke or systemic embolic event: higher dose pinteraction=0·85, lower dose pinteraction=0·99) and provided even greater safety (major bleeding: higher dose pinteraction 0·02, lower dose pinteraction=0·002). These findings validate the strategy that tailoring of the dose of edoxaban on the basis of clinical factors alone achieves the dual goal of preventing excess drug concentrations and helps to optimise an individual patient's risk of ischaemic and bleeding events and show that the therapeutic window for edoxaban is narrower for major bleeding than thromboembolism. Daiichi-Sankyo Pharma Development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Homocysteine lowering interventions for preventing cardiovascular events

PubMed Central

Martí-Carvajal, Arturo J; Solà, Ivan; Lathyris, Dimitrios; Salanti, Georgia

2014-01-01

Background Cardiovascular disease such as coronary artery disease, stroke and congestive heart failure, is a leading cause of death worldwide. A postulated risk factor is elevated circulating total homocysteine (tHcy) levels which is influenced mainly by blood levels of cyanocobalamin (vitamin B12), folic acid (vitamin B9) and pyridoxine (vitamin B6). There is uncertainty regarding the strength of association between tHcy and the risk of cardiovascular disease. Objectives To assess the clinical effectiveness of homocysteine-lowering interventions (HLI) in people with or without pre-existing cardiovascular disease. Search methods We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (issue 3 2008), MEDLINE (1950 to August 2008), EMBASE (1988 to August 2008), and LILACS (1982 to September 2, 2008). We also searched in Allied and Complementary Medicine (AMED; 1985 to August 2008), ISI Web of Science (1993 to August 2008), and the Cochrane Stroke Group Specialised Register (April 2007). We hand searched pertinent journals and the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. Selection criteria We included randomised clinical trials (RCTs) assessing the effects of HLI for preventing cardiovascular events with a follow-up period of 1 year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. Data collection and analysis We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I2. We used a random-effects model to synthesise the findings. Main results We included eight RCTs involving 24,210 participants with a low risk of bias in general terms. HLI did not reduce the risk of non-fatal or fatal myocardial infarction, stroke, or death by any cause (pooled RR 1.03, 95% CI 0.94 to 1.13, I2 = 0%; pooled RR 0.89, 95% CI 0.73 to 1.08, I2 = 15%); and pooled RR 1.00 (95% CI 0.92 to 1.09, I2: 0%), respectively. Authors’ conclusions Results from available published trials suggest that there is no evidence to support the use of HLI to prevent cardiovascular events. PMID:19821378

Effectiveness of Goal-Setting Telephone Follow-Up on Health Behaviors of Patients with Ischemic Stroke: A Randomized Controlled Trial.

PubMed

Wan, Li-Hong; Zhang, Xiao-Pei; Mo, Miao-Miao; Xiong, Xiao-Ni; Ou, Cui-Ling; You, Li-Ming; Chen, Shao-Xian; Zhang, Min

2016-09-01

Adopting healthy behaviors is critical for secondary stroke prevention, but many patients fail to follow national guidelines regarding diet, exercise, and abstinence from risk factors. Compliance often decreases with time after hospital discharge, yet few studies have examined programs promoting long-term adherence to health behaviors. Goal setting and telephone follow-up have been proven to be effective in other areas of medicine, so this study evaluated the effectiveness of a guideline-based, goal-setting telephone follow-up program for patients with ischemic stroke. This was a multicenter, assessor-blinded, parallel-group, randomized controlled trial. Ninety-one stroke patients were randomized to either a control group or an intervention group. Intervention consisted of predischarge education and 3 goal-setting follow-up sessions conducted by phone. Data were collected at baseline and during the third and sixth months after hospital discharge. Six months after discharge, patients in the intervention group exhibited significantly higher medication adherence than patients in the control group. There were no statistically significant differences in physical activity, nutrition, low-salt diet adherence, blood pressure monitoring, smoking abstinence, unhealthy use of alcohol, and modified Rankin Scale (mRS) scores between the 2 groups. Goal-setting telephone follow-up intervention for ischemic stroke patients is feasible and leads to improved medication adherence. However, the lack of group differences in other health behavior subcategories and in themRS score indicates a need for more effective intervention strategies to help patients reach guideline-recommended targets. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Clinical Correlates of Infarct Shape and Volume in Lacunar Strokes The SPS3 Trial

PubMed Central

Asdaghi, Negar; Pearce, Leasly A.; Nakajima, Makoto; Field, Thalia S; Bazan, Carlos; Cermeno, Franco; McClure, Leslie A.; Anderson, David C.; Hart, Robert G.; Benavente, Oscar R.

2014-01-01

Background and Purpose Infarct size and location are thought to correlate with different mechanisms of lacunar infarcts. We examined the relationship between the size and shape of lacunar infarcts and vascular risk factors and outcomes. Methods We studied 1679 participants in the Secondary Prevention of Small Subcortical Stroke trial with a lacunar infarct visualized on DWI. Infarct volume was measured planimetrically, and shape was classified based on visual analysis after 3D reconstruction of axial MRI slices. Results Infarct shape was ovoid/spheroid in 63%, slab 12%, stick 7%, and multi- component 17%. Median infarct volume was smallest in ovoid/spheroid relative to other shapes: 0.46, 0.65, 0.54, and 0.90 ml respectively, p< 0.001. Distributions of vascular risk factors were similar across the four groups except that patients in the ovoid/spheroid and stick groups were more often diabetic and those with multi-component had significantly higher blood pressure at study entry. Intracranial stenosis did not differ among groups (p=0.2). Infarct volume was not associated with vascular risk factors. Increased volume was associated with worse functional status at baseline and 3 months. Overall, 162 recurrent strokes occurred over an average of 3.4 years of follow-up with no difference in recurrent ischemic stroke rate by shape or volume. Conclusion In patients with recent lacunar stroke, vascular risk factor profile was similar amongst the different infarct shapes and sizes. Infarct size correlated with worse short- term functional outcome. Neither shape nor volume was predictive of stroke recurrence. PMID:25190442

What is the value of conducting a trial of r-tPA for the treatment of mild stroke patients?

PubMed

Guzauskas, Gregory F; Chen, Er; Lalla, Deepa; Yu, Elaine; Tayama, Darren; Veenstra, David L

2017-02-01

Background The Phase IIIb, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS) trial will assess r-tPA in ischemic stroke patients who present with mild deficits (i.e. mild stroke). Aims To assess PRISMS's societal value in clarifying the optimal care for patients with mild ischemic stroke. Methods A value of information (VOI) decision model was developed to compare the outcomes of mild stroke patients treated vs. not treated with r-tPA. Model inputs were derived from a subset of Third International Stroke Trial patients, a recent meta-analysis of r-tPA trials, expert opinion, and other published sources. VOI analyses were also used to assess the expected US societal value of the PRISMS trial and the expected value of reducing uncertainty in key trial estimates. Results The expected net societal value of the PRISMS trial was approximately $210 million ($160 m-$260 m), representing a six-fold return on investment. The value of reducing uncertainty in r-tPA efficacy was approximately $150 million ($100 m-$200 m), while reducing uncertainty in r-tPA safety (increased risk for symptomatic intracranial hemorrhage) did not add additional value in comparison. Conclusions Developing a better understanding of the outcomes of r-tPA treatment in patients with mild ischemic stroke will provide tremendous societal value by clarifying current uncertainty around treatment effectiveness. Enrollment in the PRISMS trial for patients presenting with mild ischemic stroke within 0-3 h of symptom onset should be highly encouraged.

Weighing the Anti-Ischemic Benefits and Bleeding Risks from Aspirin Therapy: a Rational Approach.

PubMed

Dugani, Sagar; Ames, Jeffrey M; Manson, JoAnn E; Mora, Samia

2018-02-21

The role of aspirin in secondary cardiovascular prevention is well understood; however, the role in primary prevention is less clear, and requires careful balancing of potential benefits with risks. Here, we summarize the evidence base on the benefits and risks of aspirin therapy, discuss clinical practice guidelines and decision support tools to assist in initiating aspirin therapy, and highlight ongoing trials that may clarify the role of aspirin in cardiovascular disease prevention. In 2016, the USPSTF released guidelines on the use of aspirin for primary prevention. Based on 11 trials (n = 118,445), aspirin significantly reduced all-cause mortality and nonfatal myocardial infarction, and in 7 trials that evaluated aspirin ≤ 100 mg/day, there was significant reduction in nonfatal stroke. The USPSTF recommends individualized use of aspirin based on factors including age, 10-year atherosclerotic cardiovascular disease risk score, and bleeding risk. Several ongoing trials are evaluating the role of aspirin in primary prevention, secondary prevention, and in combination therapy for atrial fibrillation. Evidence-based approaches to aspirin use should consider the anti-ischemic benefits and bleeding risks from aspirin. In this era of precision medicine, tools that provide the personalized benefit to risk assessment, such as the freely available clinical decision support tool (Aspirin-Guide), can be easily incorporated into the electronic health record and facilitate more informed decisions about initiating aspirin therapy for primary prevention. Aspirin has a complex matrix of benefits and risks, and its use in primary prevention requires individualized decision-making. Results from ongoing trials may guide healthcare providers in identifying appropriate candidates for aspirin therapy.

Adelaide stroke incidence study: declining stroke rates but many preventable cardioembolic strokes.

PubMed

Leyden, James M; Kleinig, Timothy J; Newbury, Jonathan; Castle, Sally; Cranefield, Jennifer; Anderson, Craig S; Crotty, Maria; Whitford, Deirdre; Jannes, Jim; Lee, Andrew; Greenhill, Jennene

2013-05-01

Stroke incidence rates are in flux worldwide because of evolving risk factor prevalence, risk factor control, and population aging. Adelaide Stroke Incidence Study was performed to determine the incidence of strokes and stroke subtypes in a relatively elderly population of 148 000 people in the Western suburbs of Adelaide. All suspected strokes were identified and assessed in a 12-month period from 2009 to 2010. Standard definitions for stroke and stroke fatality were used. Ischemic stroke pathogenesis was classified by the Trial of ORG 10172 in Acute Stroke Treatment criteria. There were 318 stroke events recorded in 301 individuals; 238 (75%) were first-in-lifetime events. Crude incidence rates for first-ever strokes were 161 per 100 000 per year overall (95% confidence interval [CI], 141-183), 176 for men (95% CI, 147-201), and 146 for women (95% CI, 120-176). Adjusted to the world population rates were 76 overall (95% CI, 59-94), 91 for men (95% CI, 73-112), and 61 for women (95% CI, 47-78). The 28-day case fatality rate for first-ever stroke was 19% (95% CI, 14-24); the majority were ischemic (84% [95% CI, 78-88]). Intracerebral hemorrhage comprised 11% (8-16), subarachnoid hemorrhage 3% (1-6), and 3% (1-6) were undetermined. Of the 258 ischemic strokes, 42% (95% CI, 36-49) were of cardioembolic pathogenesis. Atrial fibrillation accounted for 36% of all ischemic strokes, of which 85% were inadequately anticoagulated. Stroke incidence in Adelaide has not increased compared with previous Australian studies, despite the aging population. Cardioembolic strokes are becoming a higher proportion of all ischemic strokes.

Statistical analysis plan for the family-led rehabilitation after stroke in India (ATTEND) trial: A multicenter randomized controlled trial of a new model of stroke rehabilitation compared to usual care.

PubMed

Billot, Laurent; Lindley, Richard I; Harvey, Lisa A; Maulik, Pallab K; Hackett, Maree L; Murthy, Gudlavalleti Vs; Anderson, Craig S; Shamanna, Bindiganavale R; Jan, Stephen; Walker, Marion; Forster, Anne; Langhorne, Peter; Verma, Shweta J; Felix, Cynthia; Alim, Mohammed; Gandhi, Dorcas Bc; Pandian, Jeyaraj Durai

2017-02-01

Background In low- and middle-income countries, few patients receive organized rehabilitation after stroke, yet the burden of chronic diseases such as stroke is increasing in these countries. Affordable models of effective rehabilitation could have a major impact. The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke. Objective To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding. Methods Based upon the published registration and protocol, the blinded steering committee and management team, led by the trial statistician, have developed a statistical analysis plan. The plan has been informed by the chosen outcome measures, the data collection forms and knowledge of key baseline data. Results The resulting statistical analysis plan is consistent with best practice and will allow open and transparent reporting. Conclusions Publication of the trial statistical analysis plan reduces potential bias in trial reporting, and clearly outlines pre-specified analyses. Clinical Trial Registrations India CTRI/2013/04/003557; Australian New Zealand Clinical Trials Registry ACTRN1261000078752; Universal Trial Number U1111-1138-6707.

Stroke: Hope through Research

MedlinePlus

... the Barthel Index. Imaging for the Diagnosis of Acute Stroke Health care professionals also use a variety ... risk population. top Ongoing Clinical Trials Albumin in Acute Ischemic Stroke (ALIAS) Trial Human serum albumin is ...

Primary prevention of cardiovascular disease through population-wide motivational strategies: insights from using smartphones in stroke prevention

PubMed Central

Feigin, Valery L; Norrving, Bo; Mensah, George A

2017-01-01

The fast increasing stroke burden across all countries of the world suggests that currently used primary stroke and cardiovascular disease (CVD) prevention strategies are not sufficiently effective. In this article, we overview the gaps in, and pros and cons of, population-wide and high-risk prevention strategies. We suggest that motivating and empowering people to reduce their risk of having a stroke/CVD by using increasingly used smartphone technologies would bridge the gap in the population-wide and high-risk prevention strategies and reduce stroke/CVD burden worldwide. We emphasise that for primary stroke prevention to be effective, the focus should be shifted from high-risk prevention to prevention at any level of CVD risk, with the focus on behavioural risk factors. Such a motivational population-wide strategy could open a new page in primary prevention of not only stroke/CVD but also other non-communicable disorders worldwide. PMID:28589034

Primary prevention of cardiovascular disease through population-wide motivational strategies: insights from using smartphones in stroke prevention.

PubMed

Feigin, Valery L; Norrving, Bo; Mensah, George A

2016-01-01

The fast increasing stroke burden across all countries of the world suggests that currently used primary stroke and cardiovascular disease (CVD) prevention strategies are not sufficiently effective. In this article, we overview the gaps in, and pros and cons of, population-wide and high-risk prevention strategies. We suggest that motivating and empowering people to reduce their risk of having a stroke/CVD by using increasingly used smartphone technologies would bridge the gap in the population-wide and high-risk prevention strategies and reduce stroke/CVD burden worldwide. We emphasise that for primary stroke prevention to be effective, the focus should be shifted from high-risk prevention to prevention at any level of CVD risk, with the focus on behavioural risk factors. Such a motivational population-wide strategy could open a new page in primary prevention of not only stroke/CVD but also other non-communicable disorders worldwide.

The network of Shanghai Stroke Service System (4S): A public health-care web-based database using automatic extraction of electronic medical records.

PubMed

Dong, Yi; Fang, Kun; Wang, Xin; Chen, Shengdi; Liu, Xueyuan; Zhao, Yuwu; Guan, Yangtai; Cai, Dingfang; Li, Gang; Liu, Jianmin; Liu, Jianren; Zhuang, Jianhua; Wang, Panshi; Chen, Xin; Shen, Haipeng; Wang, David Z; Xian, Ying; Feng, Wuwei; Campbell, Bruce Cv; Parsons, Mark; Dong, Qiang

2018-07-01

Background Several stroke outcome and quality control projects have demonstrated the success in stroke care quality improvement through structured process. However, Chinese health-care systems are challenged with its overwhelming numbers of patients, limited resources, and large regional disparities. Aim To improve quality of stroke care to address regional disparities through process improvement. Method and design The Shanghai Stroke Service System (4S) is established as a regional network for stroke care quality improvement in the Shanghai metropolitan area. The 4S registry uses a web-based database that automatically extracts data from structured electronic medical records. Site-specific education and training program will be designed and administrated according to their baseline characteristics. Both acute reperfusion therapies including thrombectomy and thrombolysis in the acute phase and subsequent care were measured and monitored with feedback. Primary outcome is to evaluate the differences in quality metrics between baseline characteristics (including rate of thrombolysis in acute stroke and key performance indicators in secondary prevention) and post-intervention. Conclusions The 4S system is a regional stroke network that monitors the ongoing stroke care quality in Shanghai. This project will provide the opportunity to evaluate the spectrum of acute stroke care and design quality improvement processes for better stroke care. A regional stroke network model for quality improvement will be explored and might be expanded to other large cities in China. Clinical Trial Registration-URL http://www.clinicaltrials.gov . Unique identifier: NCT02735226.

Effects of virtual reality for stroke individuals based on the International Classification of Functioning and Health: a systematic review.

PubMed

Palma, Gisele Carla Dos Santos; Freitas, Tatiana Beline; Bonuzzi, Giordano Márcio Gatinho; Soares, Marcos Antonio Arlindo; Leite, Paulo Henrique Wong; Mazzini, Natália Araújo; Almeida, Murilo Ruas Groschitz; Pompeu, José Eduardo; Torriani-Pasin, Camila

2017-05-01

This review determines the effects of virtual reality interventions for stroke subjects based on the International Classification of Functioning, Disability,and Health (ICF) framework. Virtual reality is a promising tool for therapy for stroke rehabilitation, but the effects of virtual reality interventions on post-stroke patients based on the specific ICF domains (Body Structures, Body Functions, Activity, and Participation) have not been investigated. A systematic review was conducted, including trials with adults with a clinical diagnosis of a chronic, subacute, or acute stroke. Eligible trials had to include studies with an intervention protocol and follow-up, with a focus on upper limbs and/or lower limbs and/or balance. The Physiotherapy Evidence Database (PEDro) was used to assess the methodological quality of randomized controlled trials. Each trial was separated according to methodological quality into a high-quality trial (PEDro ≥ 6) and a low-quality trial (PEDro ≤ 6). Only high-quality trials were analyzed specifically based on the outcome of these trials. In total, 54 trials involving 1811 participants were included. Of the papers included and considered high quality, 14 trials evaluated areas of the Body Structures component, 20 trials of the Body Functions domain, 17 trials of the Activity component, and 8 trials of the Participation domain. In relation to ICF Part 2, four trials evaluated areas of the Personal Factors component and one trial evaluated domains of the Environmental Factors component. The effects of virtual reality on stroke rehabilitation based on the ICF framework are positive in Body Function and Body Structure. However, the results in the domains Activity and Participation are inconclusive. More high-quality clinical trials are needed to confirm the effectiveness of virtual reality in the domains of Activity and Participation.

Closure of Patent Foramen Ovale Versus Medical Therapy in Patients With Cryptogenic Stroke or Transient Ischemic Attack: Updated Systematic Review and Meta-Analysis.

PubMed

Ntaios, George; Papavasileiou, Vasileios; Sagris, Dimitrios; Makaritsis, Konstantinos; Vemmos, Konstantinos; Steiner, Thorsten; Michel, Patrik

2018-02-01

Previous systematic reviews and meta-analyses compared the efficacy and safety of patent foramen ovale (PFO) closure versus medical treatment in patients with cryptogenic stroke or transient ischemic attack (TIA). Recently, new evidence from randomized trials became available. We searched PubMed until September 24, 2017, for trials comparing PFO closure with medical treatment in patients with cryptogenic stroke/TIA using the items: stroke or cerebrovascular accident or TIA and patent foramen ovale or paradoxical embolism and trial or study. Among 851 identified articles, 5 were eligible. In 3627 patients with 3.7-year mean follow-up, there was significant difference in ischemic stroke recurrence (0.53 versus 1.1 per 100 patient-years, respectively; odds ratio [OR], 0.43; 95% confidence intervals (CI), 0.21-0.90; relative risk reduction, 50.5%; absolute risk reduction, 2.11%; and number needed to treat to prevent 1 event, 46.5 for 3.7 years). There was no significant difference in TIAs (0.78 versus 0.98 per 100 patient-years, respectively; OR, 0.80; 95% CI, 0.53-1.19) and all-cause mortality (0.18 versus 0.23 per 100 patient-years, respectively; OR, 0.73; 95% CI, 0.34-1.56). New-onset atrial fibrillation occurred more frequently in the PFO closure arm (1.3 versus 0.25 per 100 patient-years, respectively; OR, 5.15; 95% CI, 2.18-12.15) and resolved in 72% of cases within 45 days, whereas rates of myocardial infarction (0.12 versus 0.09 per 100 patient-years, respectively; OR, 1.22; 95% CI, 0.25-5.91) and any serious adverse events (7.3 versus 7.3 per 100 patient-years, respectively; OR, 1.07; 95% CI, 0.92-1.25) were similar. In patients with cryptogenic stroke/TIA and PFO who have their PFO closed, ischemic stroke recurrence is less frequent compared with patients receiving medical treatment. Atrial fibrillation is more frequent but mostly transient. There is no difference in TIA, all-cause mortality, or myocardial infarction. © 2018 American Heart Association, Inc.

Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial.

PubMed

Bousser, Marie-Germaine; Amarenco, Pierre; Chamorro, Angel; Fisher, Marc; Ford, Ian; Fox, Kim M; Hennerici, Michael G; Mattle, Heinrich P; Rothwell, Peter M; de Cordoüe, Agnès; Fratacci, Marie-Dominique

2011-06-11

Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke or other cardiovascular events. We compared the selective thromboxane-prostaglandin receptor antagonist terutroban with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent non-cardioembolic cerebral ischaemic event. This randomised, double-blind, parallel-group trial was undertaken in 802 centres in 46 countries. Patients who had an ischaemic stroke in the previous 3 months or a TIA in the previous 8 days were randomly allocated with a central interactive response system to 30 mg per day terutroban or 100 mg per day aspirin. Patients and investigators were masked to treatment allocation. The primary efficacy endpoint was a composite of fatal or non-fatal ischaemic stroke, fatal or non-fatal myocardial infarction, or other vascular death (excluding haemorrhagic death). We planned a sequential statistical analysis of non-inferiority (margin 1·05) followed by analysis of superiority. Analysis was by intention to treat. The study was stopped prematurely for futility on the basis of the recommendation of the Data Monitoring Committee. This study is registered, number ISRCTN66157730. 9562 patients were assigned to terutroban (9556 analysed) and 9558 to aspirin (9544 analysed); mean follow-up was 28·3 months (SD 7·7). The primary endpoint occurred in 1091 (11%) patients receiving terutroban and 1062 (11%) receiving aspirin (hazard ratio [HR] 1·02, 95% CI 0·94-1·12). There was no evidence of a difference between terutroban and aspirin for the secondary or tertiary endpoints. We recorded some increase in minor bleedings with terutroban compared with aspirin (1147 [12%] vs 1045 [11%]; HR 1·11, 95% CI 1·02-1·21), but no significant differences in other safety endpoints. The trial did not meet the predefined criteria for non-inferiority, but showed similar rates of the primary endpoint with terutroban and aspirin, without safety advantages for terutroban. In a worldwide perspective, aspirin remains the gold standard antiplatelet drug for secondary stroke prevention in view of its efficacy, tolerance, and cost. Servier, France. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genetic Associations with Plasma B12, B6, and Folate Levels in an Ischemic Stroke Population from the Vitamin Intervention for Stroke Prevention (VISP) Trial.

PubMed

Keene, Keith L; Chen, Wei-Min; Chen, Fang; Williams, Stephen R; Elkhatib, Stacey D; Hsu, Fang-Chi; Mychaleckyj, Josyf C; Doheny, Kimberly F; Pugh, Elizabeth W; Ling, Hua; Laurie, Cathy C; Gogarten, Stephanie M; Madden, Ebony B; Worrall, Bradford B; Sale, Michele M

2014-01-01

B vitamins play an important role in homocysteine metabolism, with vitamin deficiencies resulting in increased levels of homocysteine and increased risk for stroke. We performed a genome-wide association study (GWAS) in 2,100 stroke patients from the Vitamin Intervention for Stroke Prevention (VISP) trial, a clinical trial designed to determine whether the daily intake of high-dose folic acid, vitamins B6, and B12 reduce recurrent cerebral infarction. Extensive quality control (QC) measures resulted in a total of 737,081 SNPs for analysis. Genome-wide association analyses for baseline quantitative measures of folate, Vitamins B12, and B6 were completed using linear regression approaches, implemented in PLINK. Six associations met or exceeded genome-wide significance (P ≤ 5 × 10(-08)). For baseline Vitamin B12, the strongest association was observed with a non-synonymous SNP (nsSNP) located in the CUBN gene (P = 1.76 × 10(-13)). Two additional CUBN intronic SNPs demonstrated strong associations with B12 (P = 2.92 × 10(-10) and 4.11 × 10(-10)), while a second nsSNP, located in the TCN1 gene, also reached genome-wide significance (P = 5.14 × 10(-11)). For baseline measures of Vitamin B6, we identified genome-wide significant associations for SNPs at the ALPL locus (rs1697421; P = 7.06 × 10(-10) and rs1780316; P = 2.25 × 10(-08)). In addition to the six genome-wide significant associations, nine SNPs (two for Vitamin B6, six for Vitamin B12, and one for folate measures) provided suggestive evidence for association (P ≤ 10(-07)). Our GWAS study has identified six genome-wide significant associations, nine suggestive associations, and successfully replicated 5 of 16 SNPs previously reported to be associated with measures of B vitamins. The six genome-wide significant associations are located in gene regions that have shown previous associations with measures of B vitamins; however, four of the nine suggestive associations represent novel finding and warrant further investigation in additional populations.

Combining Standard Conventional Measures and Ecological Momentary Assessment of Depression, Anxiety and Coping Using Smartphone Application in Minor Stroke Population: A Longitudinal Study Protocol

PubMed Central

Vansimaeys, Camille; Zuber, Mathieu; Pitrat, Benjamin; Join-Lambert, Claire; Tamazyan, Ruben; Farhat, Wassim; Bungener, Catherine

2017-01-01

Context: Stroke has several consequences on survivors’ daily life even for those who experience short-lasting neurological symptoms with no functional disability. Depression and anxiety are common psychological disorders occurring after a stroke. They affect long-term outcomes and quality of life but they are difficult to diagnose because of the neurobiological consequences of brain lesions. Current research priority is given to the improvement of the detection and prevention of those post-stroke psychological disorders. Although previous studies have brought promising perspectives, their designs based on retrospective tools involve some limits regarding their ecological validity. Ecological Momentary Assessment (EMA) is an alternative to conventional instruments that could be a key in research for understanding processes that underlined post-stroke depression and anxiety onset. We aim to evaluate the feasibility and validity of anxiety, depression and coping EMA for minor stroke patients. Methods: Patients hospitalized in an Intensive Neuro-vascular Care Unit between April 2016 and January 2017 for a minor stroke is involved in a study based on an EMA methodology. We use a smartphone application in order to assess anxiety and depression symptoms and coping strategies four times a day during 1 week at three different times after stroke (hospital discharge, 2 and 4 months). Participants’ self-reports and clinician-rates of anxiety, depression and coping are collected simultaneously using conventional and standard instruments. Feasibility of the EMA method will be assessed considering the participation and compliance rate. Validity will be the assessed by comparing EMA and conventional self-report and clinician-rated measures. Discussion: We expect this study to contribute to the development of EMA using smartphone in minor stroke population. EMA method offers promising research perspective in the assessment and understanding of post-stroke psychological disorders. The development of EMA in stroke population could lead to clinical implications such as remotely psychological follow-ups during early supported discharge. Trial registration: European Clinical Trials Database Number 2014-A01937-40 PMID:28747895

Diets enriched in whey or casein improve energy balance and prevent morbidity and renal damage in salt-loaded and high-fat-fed spontaneously hypertensive stroke-prone rats.

PubMed

Singh, Arashdeep; Pezeshki, Adel; Zapata, Rizaldy C; Yee, Nicholas J; Knight, Cameron G; Tuor, Ursula I; Chelikani, Prasanth K

2016-11-01

High-fat diets induce obesity and increase risks of diabetes and cardiovascular and renal disorders. Whey- or casein-enriched diets decrease food intake and weight gain; however, their cardiovascular and renal benefits are unclear. We determined whether whey- and casein-enriched diets improve energy balance and are protective against renal damage and morbidity associated with stroke in an obesogenic and hypertensive experimental setting. We also assessed whether the hypophagic effects of these diets were due to reduced diet preference. In experiment 1, spontaneously hypertensive stroke-prone rats were randomized to (a) control (CON; 14% kcal protein, 33% fat), (b) whey (WHY; 40% protein, 33% fat), (c) casein (CAS; 40% protein, 33% fat) or (d) chow (CHW; 24% protein, 13% fat) for 12 weeks with 1% salt in drinking water for CON, WHY and CAS groups. Our results demonstrated that both WHY and CAS produced short-term hypophagia, moderately increased energy expenditure and decreased respiratory quotient, body weight and lean mass, with effects of WHY being more prolonged. Further, only WHY decreased fat mass and blood pressure. Importantly, both WHY and CAS prevented morbidity associated with stroke and decreased indices of renal inflammation (tumor necrosis factor-α, interleukin-6) and damage (osteopontin, renal lesions). In experiment 2, following four initial conditioning trials, the preference for CON, WHY or CAS diet was determined. Both WHY and CAS decreased food intake during conditioning and decreased preference. In conclusion, diets enriched in whey or casein improved energy balance, increased survival and prevented renal damage in salt-loaded and high-fat-fed spontaneously hypertensive stroke-prone rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost-Effectiveness of Apixaban Compared with Warfarin for Stroke Prevention in Atrial Fibrillation

PubMed Central

Lee, Soyon; Mullin, Rachel; Blazawski, Jon; Coleman, Craig I.

2012-01-01

Background Apixaban was shown to be superior to adjusted-dose warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation (AF) and at least one additional risk factor for stroke, and associated with reduced rates of hemorrhage. We sought to determine the cost-effectiveness of using apixaban for stroke prevention. Methods Based on the results from the Apixaban Versus Warfarin in Patients with Atrial Fibrillation (ARISTOTLE) trial and other published studies, we constructed a Markov model to evaluate the cost-effectiveness of apixaban versus warfarin from the Medicare perspective. The base-case analysis assumed a cohort of 65-year-old patients with a CHADS2 score of 2.1 and no contraindication to oral anticoagulation. We utilized a 2-week cycle length and a lifetime time horizon. Outcome measures included costs in 2012 US$, quality-adjusted life-years (QALYs), life years saved and incremental cost-effectiveness ratios. Results Under base case conditions, quality adjusted life expectancy was 10.69 and 11.16 years for warfarin and apixaban, respectively. Total costs were $94,941 for warfarin and $86,007 for apixaban, demonstrating apixaban to be a dominant economic strategy. Upon one-way sensitivity analysis, these results were sensitive to variability in the drug cost of apixaban and various intracranial hemorrhage related variables. In Monte Carlo simulation, apixaban was a dominant strategy in 57% of 10,000 simulations and cost-effective in 98% at a willingness-to-pay threshold of $50,000 per QALY. Conclusions In patients with AF and at least one additional risk factor for stroke and a baseline risk of ICH risk of about 0.8%, treatment with apixaban may be a cost-effective alternative to warfarin. PMID:23056642

Optimizing stroke clinical trial design: estimating the proportion of eligible patients.

PubMed

Taylor, Alexis; Castle, Amanda; Merino, José G; Hsia, Amie; Kidwell, Chelsea S; Warach, Steven

2010-10-01

Clinical trial planning and site selection require an accurate estimate of the number of eligible patients at each site. In this study, we developed a tool to calculate the proportion of patients who would meet a specific trial's age, baseline severity, and time to treatment inclusion criteria. From a sample of 1322 consecutive patients with acute ischemic cerebrovascular syndromes, we developed regression curves relating the proportion of patients within each range of the 3 variables. We used half the patients to develop the model and the other half to validate it by comparing predicted vs actual proportions who met the criteria for 4 current stroke trials. The predicted proportion of patients meeting inclusion criteria ranged from 6% to 28% among the different trials. The proportion of trial-eligible patients predicted from the first half of the data were within 0.4% to 1.4% of the actual proportion of eligible patients. This proportion increased logarithmically with National Institutes of Health Stroke Scale score and time from onset; lowering the baseline limits of the National Institutes of Health Stroke Scale score and extending the treatment window would have the greatest impact on the proportion of patients eligible for a stroke trial. This model helps estimate the proportion of stroke patients eligible for a study based on different upper and lower limits for age, stroke severity, and time to treatment, and it may be a useful tool in clinical trial planning.

A new theory of cryptogenic stroke and its relationship to patent foramen ovale; or, the puzzle of the missing extra risk.

PubMed

Eggers, Arnold E

2006-01-01

Cryptogenic stroke (or stroke of undetermined cause) is a common cause of stroke and is statistically associated with patent foramen ovale (PFO). The largest study of cryptogenic stroke is the Homma study, which is a sub-study of the WARSS trial; it produced the following data: cryptogenic stroke patients with and without PFO, when treated with either aspirin or warfarin, all had identical recurrence rates. This is puzzling because it seems as though there ought to have been some extra risk in one of the two groups under one of the two treatments. How could everything come out the same? A review of the epidemiology of cryptogenic stroke shows that, compared to patients with stroke of determined cause, cryptogenic stroke patients are a little younger and have lower doses of the usual risk factors (hypertension and diabetes mellitus) but more PFO. Cryptogenic strokes appear to be embolic strokes from an unknown source. A previously published article setting forth a hypothetical theory of stress-induced stroke was used to analyze these data. It is suggested that stress can induce episodic systemic platelet activation and hypercoagulability, which causes transient thrombus formation and subsequent embolization on both the arterial and venous sides of the circulation; the latter requires a PFO to cause a stroke (paradoxical embolism). The sum of these two mechanisms explains cryptogenic stroke. The PFO subset of cryptogenic stroke includes patients with both early and late stage disease who have an aggregate risk approximately equal to that of patients without PFO. Cryptogenic stroke is part of the disease of stress-induced cerebrovascular disease. Aspirin and warfarin have already been shown to be equally effective in secondary prevention of ischemic stroke.

Symptomatic and asymptomatic carotid artery plaque

PubMed Central

Mughal, Majid M; Khan, Mohsin K; DeMarco, J Kevin; Majid, Arshad; Shamoun, Fadi; Abela, George S

2011-01-01

Carotid atherosclerotic plaques represent both stable and unstable atheromatous lesions. Atherosclerotic plaques that are prone to rupture owing to their intrinsic composition such as a large lipid core, thin fibrous cap and intraplaque hemorrhage are associated with subsequent thromboembolic ischemic events. At least 15–20% of all ischemic strokes are attributable to carotid artery atherosclerosis. Characterization of plaques may enhance the understanding of natural history and ultimately the treatment of atherosclerotic disease. MRI of carotid plaque and embolic signals during transcranial Doppler have identified features beyond luminal stenosis that are predictive of future transient ischemic attacks and stroke. The value of specific therapies to prevent stroke in symptomatic and asymptomatic patients with severe carotid artery stenosis are the subject of current research and analysis of recently published clinical trials that are discussed in this article. PMID:21985544

Delayed-onset dementia after stroke or transient ischemic attack.

PubMed

Mok, Vincent C T; Lam, Bonnie Y K; Wang, Zhaolu; Liu, Wenyan; Au, Lisa; Leung, Eric Y L; Chen, Sirong; Yang, Jie; Chu, Winnie C W; Lau, Alexander Y L; Chan, Anne Y Y; Shi, Lin; Fan, Florence; Ma, Sze H; Ip, Vincent; Soo, Yannie O Y; Leung, Thomas W H; Kwok, Timothy C Y; Ho, Chi L; Wong, Lawrence K S; Wong, Adrian

2016-11-01

Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Comprehensive cardiac rehabilitation for secondary prevention after transient ischemic attack or mild stroke: I: feasibility and risk factors.

PubMed

Prior, Peter L; Hachinski, Vladimir; Unsworth, Karen; Chan, Richard; Mytka, Sharon; O'Callaghan, Christina; Suskin, Neville

2011-11-01

Comprehensive cardiac rehabilitation (CCR), which integrates structured lifestyle interventions and medications, reduces morbidity and mortality among cardiac patients. CCR has not typically been used with cerebrovascular populations, despite important commonalities with heart patients. We tested feasibility and effectiveness of 6-month outpatient CCR for secondary prevention after transient ischemic attack or mild, nondisabling stroke. This article presents risk factors. A future article will discuss psychological outcomes. Consecutive consenting subjects having sustained a transient ischemic attack or mild, nondisabling stroke within the previous 12 months (mean, 11.5 weeks; event-to-CCR entry) with ≥1 vascular risk factor, were recruited from a stroke prevention clinic providing usual care. We measured 6-month CCR outcomes following a prospective cohort design. Of 110 subjects recruited from January 2005 to April 2006, 100 subjects (mean age, 64.9 years; 46 women) entered and 80 subjects completed CCR. We obtained favorable, significant intake-to-exit changes in: aerobic capacity (+31.4%; P<0.001), total cholesterol (-0.30 mmol/L; P=0.008), total cholesterol/high-density lipoprotein (-11.6%; P<0.001), triglycerides (-0.27 mmol/L; P=0.003), waist circumference (-2.44 cm; P<0.001), body mass index (-0.53 kg/m(2); P=0.003), and body weight (-1.43 kg; P=0.001). Low-density lipoprotein (-0.24 mmol/L), high-density lipoprotein (+0.06 mmol/L), systolic (-3.21 mm Hg) and diastolic (-2.34 mm Hg) blood pressure changed favorably, but nonsignificantly. A significant shift toward nonsmoking occurred (P=0.008). Compared with intake, 11 more individuals (25.6% increase) finished CCR in the lowest-mortality risk category of the Duke Treadmill Score (P<0.001). CCR is feasible and effective for secondary prevention after transient ischemic attack or mild, nondisabling stroke, offering a promising model for vascular protection across chronic disease entities. We know of no similar previous investigation, and are now conducting a randomized trial.

OCULUS study: Virtual reality-based education in daily clinical practice.

PubMed

Balsam, Paweł; Borodzicz, Sonia; Malesa, Karolina; Puchta, Dominika; Tymińska, Agata; Ozierański, Krzysztof; Kołtowski, Łukasz; Peller, Michał; Grabowski, Marcin; Filipiak, Krzysztof J; Opolski, Grzegorz

2018-01-03

Atrial fibrillation (AF) is associated with high risk of stroke and other thromboembolic complications. The OCULUS study aimed to evaluate the effectiveness of the three-dimensional (3D) movie in teaching patients about the consequences of AF and pharmacological stroke prevention. The study was based on a questionnaire and included 100 consecutive patients (38% women, 62% with AF history). Using the oculus glasses and a smartphone, a 3D movie describing the risk of stroke in AF was shown. Similar questions were asked immediately after, 1 week and 1 year after the projection. Before the projection 22/100 (22.0%) declared stroke a consequence of AF, while immediately after 83/100 (83.0%) (p < 0.0001)patients declared this consequence. Seven days after, stroke as AF consequence was chosen by 74/94 (78.7%) vs. 22/94 (23.4%) when compared to the baseline knowledge; p < 0.0001, a similar trend was also observed in one-year follow-up (64/90 [71.1%] vs. 21/90 [23.3%]; p < 0.0001). Before the projection 88.3% (83/94) patients responded, that drugs may reduce the risk of stroke, and after 1 week the number of patients increased to (94/94 [100%]; p = 0.001). After 1 year 87/90 (96.7%) answered that drugs may diminish the risk of stroke (p = 0.02 in comparison to the baseline survey 78/90 [86.7%]). Use of OAC to reduce the risk of stroke was initially chosen by 66/94 (70.2%), by 90/94 (95.7%; p < 0.0001) 7 days after and by 83/90 (92.2%; p < 0.0001) one year after. 3D movie is an effective tool in transferring knowledge about the consequences of AF and the pivotal role of OAC in stroke prevention. ClinicalTrials.gov, NCT03104231. Registered on 28 March 2017.

Safety and effectiveness of stem cell therapies in early-phase clinical trials in stroke: a systematic review and meta-analysis.

PubMed

Nagpal, Anjali; Choy, Fong Chan; Howell, Stuart; Hillier, Susan; Chan, Fiona; Hamilton-Bruce, Monica A; Koblar, Simon A

2017-08-30

Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

Is primary care a neglected piece of the jigsaw in ensuring optimal stroke care? Results of a national study

PubMed Central

Whitford, David L; Hickey, Anne; Horgan, Frances; O'Sullivan, Bernadette; McGee, Hannah; O'Neill, Desmond

2009-01-01

Background Stroke is a major cause of mortality and morbidity with potential for improved care and prevention through general practice. A national survey was undertaken to determine current resources and needs for optimal stroke prevention and care. Methods Postal survey of random sample of general practitioners undertaken (N = 204; 46% response). Topics included practice organisation, primary prevention, acute management, secondary prevention, long-term care and rehabilitation. Results Service organisation for both primary and secondary prevention was poor. Home management of acute stroke patients was used at some stage by 50% of responders, accounting for 7.3% of all stroke patients. Being in a structured cardiovascular management scheme, a training practice, a larger practice, or a practice employing a practice nurse were associated with structures and processes likely to support stroke prevention and care. Conclusion General practices were not fulfilling their potential to provide stroke prevention and long-term management. Systems of structured stroke management in general practice are essential to comprehensive national programmes of stroke care. PMID:19402908

Menopausal hormone therapy for the primary prevention of chronic conditions: a systematic review to update the U.S. Preventive Services Task Force recommendations.

PubMed

Nelson, Heidi D; Walker, Miranda; Zakher, Bernadette; Mitchell, Jennifer

2012-07-17

Menopausal hormone therapy to prevent chronic conditions is currently not recommended because of its adverse effects. To update evidence about the effectiveness of hormone therapy in reducing risk for chronic conditions and adverse effects, and to examine whether outcomes vary among women in different subgroups. MEDLINE (January 2002 to November 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the 3rd quarter of 2011), Scopus, and reference lists. Randomized, placebo-controlled trials of menopausal hormone therapy published in English since 2002 that assessed primary prevention of chronic conditions. Investigators extracted data on participants, study design, analysis, follow-up, and results; 2 investigators independently rated study quality by using established criteria. 9 fair-quality trials met the inclusion criteria. The Women's Health Initiative reported most of the results, had 11 years of follow-up, and had data most applicable to postmenopausal women in the United States. It showed that estrogen plus progestin therapy reduced fractures (46 fewer per 10 000 woman-years) and increased invasive breast cancer (8 more per 10 000 woman-years), stroke (9 more per 10 000 woman-years), deep venous thrombosis (12 more per 10 000 woman-years), pulmonary embolism (9 more per 10 000 woman-years), lung cancer death (5 more per 10 000 woman-years), gallbladder disease (20 more per 10 000 woman-years), dementia (22 more per 10 000 woman-years), and urinary incontinence (872 more per 10 000 woman-years). Estrogen-only therapy reduced fractures (56 fewer per 10 000 woman-years), invasive breast cancer (8 fewer per 10 000 woman-years), and death (2 fewer per 10 000 woman-years) and increased stroke (11 more per 10 000 woman-years), deep venous thrombosis (7 more per 10 000 woman-years), gallbladder disease (33 more per 10 000 woman-years), and urinary incontinence (1271 more per 10 000 woman-years). Outcomes did not consistently differ by age or comorbid conditions. Limitations of the trials included low adherence, high attrition, inadequate power to detect risks for some outcomes, and evaluation of few regimens. Estrogen plus progestin and estrogen alone decreased risk for fractures but increased risk for stroke, thromboembolic events, gallbladder disease, and urinary incontinence. Estrogen plus progestin increased risk for breast cancer and probable dementia, whereas estrogen alone decreased risk for breast cancer. Agency for Healthcare Research and Quality.

Swipe out Stroke: Feasibility and efficacy of using a smart-phone based mobile application to improve compliance with weight loss in obese minority stroke patients and their carers.

PubMed

Ifejika, Nneka Lotea; Noser, Elizabeth Anne; Grotta, James C; Savitz, Sean I

2016-07-01

Swipe out Stroke (SOS) examines the use of a smartphone-based mobile application to reduce obesity in high-risk minority stroke patients. At record-high levels in the United States, obesity disproportionately affects minorities and is highly correlated with cerebrovascular disease. Unfortunately, structured weight loss programs are expensive, and compliance significantly decreases upon program completion. Mobile health (mHealth) technology is an innovative, cost-effective way to bridge this gap. Minorities spend over 4.5 billion dollars annually on consumer electronics, making studies that utilize mHealth applications ideal for health promotion and disease prevention. SOS is a prospective, randomized-controlled trial with open blinded endpoint comparing an mHealth based dietary intervention to usual care to facilitate weight reduction. Ischemic and hemorrhagic stroke survivors and their carers are recruited from the acute care service of a Houston-based comprehensive stroke center. A neurorehabilitation physician or vascular neurologist meets with participants during the index hospitalization, a baseline clinic visit, followed by visits at 1, 3, and 6 month intervals. The SOS Team focuses on feasible modifications to the Southern dietary pattern (fried foods, fatty foods, added fats, eggs, processed meats, such as bacon and ham, organ meats (e.g., liver), and sweetened drinks) and caloric restriction to facilitate a 5% reduction in total body weight. Practical barriers to adherence are addressed, such as access to transportation, financial limitations, and depression. The primary dependent measure is a reduction of total body weight. Secondary outcomes include systolic blood pressure, hemoglobin A1c, low-density lipoprotein, triglycerides, and Factor VIII. SOS will determine whether a Phase III effectiveness trial of a smartphone-based mobile application to address obesity-related health disparities is warranted throughout the Southeastern United States (Stroke Belt). © 2016 World Stroke Organization.

Edoxaban versus placebo, aspirin, or aspirin plus clopidogrel for stroke prevention in atrial fibrillation. An indirect comparison analysis.

PubMed

Blann, A D; Skjøth, F; Rasmussen, L H; Larsen, T B; Lip, G Y H

2015-08-01

As non-valvular atrial fibrillation (AF) brings a risk of stroke, oral anticoagulants (OAC) are recommended. In 'real world' clinical practice, many patients (who may be, or perceived to be, intolerant of OACs) are either untreated or are treated with anti-platelet agents. We hypothesised that edoxaban has a better net clinical benefit (NCB, balancing the reduction in stroke risk vs increased risk of haemorrhage) than no treatment or anti-platelet agents. We performed a network meta-analysis of published data from 24 studies of 203,394 AF patients to indirectly compare edoxaban with aspirin alone, aspirin plus clopidogrel, and placebo. Edoxaban 30 mg once daily significantly reduced the risk of all stroke, ischaemic stroke and mortality compared to placebo and aspirin. Compared to aspirin plus clopidogrel, there was a lower risk of intra-cranial haemorrhage (ICH). Edoxaban 60 mg once-daily had a reduced risk of any stroke and systemic embolism compared to placebo, aspirin, and aspirin plus clopidogrel. Mortality rates for both edoxaban doses were estimated to be lower compared to any anti-platelet, and significantly lower compared to placebo. With overall reduced risk of ischemic stroke and ICH, both edoxaban doses bring a NCB of mean (SD) 1.68 (0.15) saved events per 100 patients per year compared to anti-platelet drugs in a clinical trial population. The NCB was demonstrated to be lower, at 0.77 (0.12) events saved (p< 0.01) when modeled to data from a 'real world' cohort of AF patients. In conclusion, edoxaban is likely to provide even better protection from stroke and ICH than placebo, aspirin alone, or aspirin plus clopidogrel in both clinical trial populations and unselected community populations. Both edoxaban doses would also bring a positive NCB compared to anti-platelet drugs or placebo/non-treatment based on 'real world' data.

A new paradigm for primary prevention strategy in people with elevated risk of stroke.

PubMed

Feigin, Valery L; Norrving, Bo

2014-07-01

Existing methods of primary stroke prevention are not sufficiently effective. Based on the recently developed Stroke Riskometer app, a new 'mass-elevated risk stroke/cardiovascular disease prevention' approach as an addition to the currently adopted absolute risk stroke/cardiovascular disease prevention approach is being advocated. We believe this approach is far more appealing to the individuals concerned and could be as efficient as the conventional population-based approach because it allows identification and engagement in prevention of all individuals who are at an increased (even slightly increased) risk of stroke and cardiovascular disease. The key novelty of this approach is twofold. First, it utilizes modern far-reaching mobile technologies, allowing individuals to calculate their absolute risk of stroke within the next 5 to 10 years and to compare their risk with those of the same age and gender without risk factors. Second, it employs self-management strategies to engage the person concerned in stroke/cardiovascular disease prevention, which is tailored to the person's individual risk profile. Preventative strategies similar to the Stroke Riskometer could be developed for other non-communicable disorders for which reliable predictive models and preventative recommendations exist. This would help reduce the burden of non-communicable disorders worldwide. © 2014 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Edoxaban vs warfarin in patients with nonvalvular atrial fibrillation in the US Food and Drug Administration approval population: An analysis from the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial.

PubMed

Eisen, Alon; Giugliano, Robert P; Ruff, Christian T; Nordio, Francesco; Gogia, Harinder S; Awasty, Vivek R; Henderson, David A; Mercuri, Michele F; Rutman, Howard; Antman, Elliott M; Braunwald, Eugene

2016-02-01

Edoxaban is a specific anti-Xa inhibitor that, in comparison to warfarin, has been found to be noninferior for the prevention of stroke or systemic embolism (SSE) and to reduce bleeding significantly in patients with nonvalvular atrial fibrillation (AF). The US Food and Drug Administration (FDA) approved the higher-dose edoxaban regimen (60/30 mg) in patients with AF and a creatinine clearance of ≤95 mL/min. We report for the first time the clinical characteristics, efficacy, and safety of the FDA-approved population in the ENGAGE AF--TIMI 48 trial. The patients included had been treated with either warfarin or edoxaban 60/30 mg and had a creatinine clearance of ≤95 mL/min. The primary efficacy was SSE, and the principal safety end point was major bleeding (International Society on Thrombosis and Haemostasis classification). Median follow-up was 2.8 years. Patients in the FDA-approved cohort were older, were more likely female, and had higher CHADS2 and HAS-BLED scores, as compared with patients not included in the FDA label. The primary end point occurred in 1.63%/y with edoxaban vs 2.02%/y with warfarin (hazard ratio [HR] 0.81, 95% CI 0.67-0.97, P = .023). Edoxaban significantly reduced the rate of hemorrhagic stroke (HR 0.47, 95% CI 0.31-0.72, P < .001) and cardiovascular death (HR 0.84, 95% CI 0.73-0.97, P = .015). Ischemic stroke rates were similar between the treatment groups (1.31%/y vs 1.39%/y, P = .97). Major bleeding was significantly lower with edoxaban (3.16%/y vs 3.77%/y; HR 0.84, 95% CI 0.72-0.98, P = .023). In the FDA-approved cohort of the ENGAGE AF--TIMI 48 trial, treatment with edoxaban 60/30 mg was superior to warfarin in the prevention of SSE and significantly reduced cardiovascular death and bleeding, especially fatal bleeding and hemorrhagic stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

SPACE-2: A Missed Opportunity to Compare Carotid Endarterectomy, Carotid Stenting, and Best Medical Treatment in Patients with Asymptomatic Carotid Stenoses.

PubMed

Eckstein, H-H; Reiff, T; Ringleb, P; Jansen, O; Mansmann, U; Hacke, W

2016-06-01

Because of recent advances in best medical treatment (BMT), it is currently unclear whether any additional surgical or endovascular interventions confer additional benefit, in terms of preventing late ipsilateral carotid territory ischemic stroke in asymptomatic patients with significant carotid stenoses. The aim was to compare the stroke-preventive effects of BMT alone, with that of BMT in combination with carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with high grade asymptomatic extracranial carotid artery stenosis. SPACE-2 was planned as a three-armed, randomized controlled trial (BMT alone vs. CEA plus BMT vs. CAS plus BMT, ISRCTN 78592017). However, because of slow patient recruitment, the three-arm study design was amended (July 2013) to become two parallel randomized studies (BMT alone vs. CEA plus BMT, and BMT alone vs. CAS plus BMT). The change in study design did not lead to any significant increase in patient recruitment, and trial recruitment ceased after recruiting 513 patients over a 5 year period (CEA vs. BMT (n = 203); CAS vs. BMT (n = 197), and BMT alone (n = 113)). The 30 day rate of death/stroke was 1.97% for patients undergoing CEA, and 2.54% for patients undergoing CAS. No strokes or deaths occurred in the first 30 days after randomization in patients randomized to BMT. There were several potential reasons for the low recruitment rates into SPACE-2, including the ability for referring doctors to refer their patients directly for CEA or CAS outwith the trial, an inability to convince patients (who had come "mentally prepared" that an intervention was necessary) to accept BMT, and other economic constraints. Because of slow recruitment rates, SPACE-2 had to be stopped after randomizing only 513 patients. The German Research Foundation will provide continued funding to enable follow up of all recruited patients, and it is also planned to include these data in any future meta-analysis prepared by the Carotid Stenosis Trialists Collaboration. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited.

PubMed

Sandercock, Peter; Lindley, Richard; Wardlaw, Joanna; Dennis, Martin; Innes, Karen; Cohen, Geoff; Whiteley, Will; Perry, David; Soosay, Vera; Buchanan, David; Venables, Graham; Czlonkowska, Anna; Kobayashi, Adam; Berge, Eivind; Slot, Karsten Bruins; Murray, Veronica; Peeters, Andre; Hankey, Graeme J; Matz, Karl; Brainin, Michael; Ricci, Stefano; Cantisani, Teresa A; Gubitz, Gordon; Phillips, Stephen J; Antonio, Arauz; Correia, Manuel; Lyrer, Phillippe; Kane, Ingrid; Lundstrom, Erik

2011-11-30

Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials. ISRCTN25765518.

Long-term follow-up of moderately hypercholesterolemic hypertensive patients following randomization to pravastatin vs. usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)

PubMed Central

Margolis, Karen L.; Davis, Barry R.; Baimbridge, Charles; Ciocon, Jerry O.; Cuyjet, Aloysius B.; Dart, Richard A.; Einhorn, Paula T.; Ford, Charles E.; Gordon, David; Hartney, Thomas J; Haywood, L. Julian; Holtzman, Jordan; Mathis, David E.; Oparil, Suzanne; Probstfield, Jeffrey L.; Simpson, Lara M.; Stokes, John D.; Wiegmann, Thomas B.; Williamson, Jeff D.

2015-01-01

A randomized, controlled, multicenter trial assigned well-controlled hypertensive participants ≥55 years, with moderate hypercholesterolemia to receive pravastatin (n=5170) or usual care (n=5185) for 4-8 years, when trial therapy was discontinued. Passive surveillance using national databases to ascertain deaths and hospitalizations continued for total follow-up of 8-13 years to assess whether mortality and morbidity differences persisted or new differences developed. During the post-trial period, fatal and nonfatal outcomes were available for 98% and 64% of participants, respectively. Primary outcome was all-cause mortality; secondary outcomes included cardiovascular mortality, coronary heart disease (CHD), stroke, heart failure, cardiovascular disease, and end-stage renal disease. No significant differences appeared in mortality for pravastatin versus usual care (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03), or other secondary outcomes. Similar to the previously reported in-trial result, there was a significant treatment effect for CHD in Blacks (HR, 0.79; 95% CI, 0.64-0.98). However, the in-trial result showing a significant treatment by race effect did not remain significant over the entire follow-up (P=.08). These findings are consistent with evidence from other large trials that show statins prevent CHD and add evidence that they are effective for CHD prevention in Blacks. PMID:23889716

Omega-3 fatty acids: benefits for cardio-cerebro-vascular diseases.

PubMed

Siegel, G; Ermilov, E

2012-12-01

Intracranial artery stenosis (ICAS) is a narrowing of an intracranial artery, which is a common etiology for ischemic stroke. In this commentary, we review key aspects of the discrimination between non-stroke controls and ischemic stroke patients on the background of phospholipid ω3-fatty acid (DHA, EPA) composition. The discussion is embedded in the presentation of general effects of long-chain ω3 polyunsaturated fatty acids (PUFAs) in cardio-cerebro-vascular diseases (CCVDs) and Alzheimer dementia (AD). ICAS is a common stroke subtype and has emerged as a major factor in recurrent stroke and vascular mortality. DHA and EPA are important fatty acids to distinguish between NCAS (no cerebral arteriosclerotic stenosis) and ICAS in stroke. The risk of ICAS is inversely correlated with the DHA content in phospholipids. Furthermore, a mechanistic explanation has been proposed for the beneficial effects of PUFAs in CCVDs and AD. Whereas the beneficial effects of EPA/DHA for cardiovascular diseases and stroke seem to be beyond question, preventive effects in patients with very mild cognitive dysfunction and beginning Alzheimer's disease undoubtedly need confirmation by larger clinical trials. A collaborative international basic science approach is warranted considering cautiously designed studies in order to avoid ethical problems. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Characterizing stroke lesions using digital templates and lesion quantification tools in a web-based imaging informatics system for a large-scale stroke rehabilitation clinical trial

NASA Astrophysics Data System (ADS)

Wang, Ximing; Edwardson, Matthew; Dromerick, Alexander; Winstein, Carolee; Wang, Jing; Liu, Brent

2015-03-01

Previously, we presented an Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) imaging informatics system that supports a large-scale phase III stroke rehabilitation trial. The ePR system is capable of displaying anonymized patient imaging studies and reports, and the system is accessible to multiple clinical trial sites and users across the United States via the web. However, the prior multicenter stroke rehabilitation trials lack any significant neuroimaging analysis infrastructure. In stroke related clinical trials, identification of the stroke lesion characteristics can be meaningful as recent research shows that lesion characteristics are related to stroke scale and functional recovery after stroke. To facilitate the stroke clinical trials, we hope to gain insight into specific lesion characteristics, such as vascular territory, for patients enrolled into large stroke rehabilitation trials. To enhance the system's capability for data analysis and data reporting, we have integrated new features with the system: a digital brain template display, a lesion quantification tool and a digital case report form. The digital brain templates are compiled from published vascular territory templates at each of 5 angles of incidence. These templates were updated to include territories in the brainstem using a vascular territory atlas and the Medical Image Processing, Analysis and Visualization (MIPAV) tool. The digital templates are displayed for side-by-side comparisons and transparent template overlay onto patients' images in the image viewer. The lesion quantification tool quantifies planimetric lesion area from user-defined contour. The digital case report form stores user input into a database, then displays contents in the interface to allow for reviewing, editing, and new inputs. In sum, the newly integrated system features provide the user with readily-accessible web-based tools to identify the vascular territory involved, estimate lesion area, and store these results in a web-based digital format.

Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial.

PubMed

Mant, Jonathan; Hobbs, F D Richard; Fletcher, Kate; Roalfe, Andrea; Fitzmaurice, David; Lip, Gregory Y H; Murray, Ellen

2007-08-11

Anticoagulants are more effective than antiplatelet agents at reducing stroke risk in patients with atrial fibrillation, but whether this benefit outweighs the increased risk of bleeding in elderly patients is unknown. We assessed whether warfarin reduced risk of major stroke, arterial embolism, or other intracranial haemorrhage compared with aspirin in elderly patients. 973 patients aged 75 years or over (mean age 81.5 years, SD 4.2) with atrial fibrillation were recruited from primary care and randomly assigned to warfarin (target international normalised ratio 2-3) or aspirin (75 mg per day). Follow-up was for a mean of 2.7 years (SD 1.2). The primary endpoint was fatal or disabling stroke (ischaemic or haemorrhagic), intracranial haemorrhage, or clinically significant arterial embolism. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN89345269. There were 24 primary events (21 strokes, two other intracranial haemorrhages, and one systemic embolus) in people assigned to warfarin and 48 primary events (44 strokes, one other intracranial haemorrhage, and three systemic emboli) in people assigned to aspirin (yearly risk 1.8%vs 3.8%, relative risk 0.48, 95% CI 0.28-0.80, p=0.003; absolute yearly risk reduction 2%, 95% CI 0.7-3.2). Yearly risk of extracranial haemorrhage was 1.4% (warfarin) versus 1.6% (aspirin) (relative risk 0.87, 0.43-1.73; absolute risk reduction 0.2%, -0.7 to 1.2). These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation, unless there are contraindications or the patient decides that the benefits are not worth the inconvenience.

Effect of Chronic Blood Transfusion on Biomarkers of Coagulation Activation and Thrombin Generation in Sickle Cell Patients at Risk for Stroke

PubMed Central

Hyacinth, Hyacinth I.; Adams, Robert J.; Greenberg, Charles S.; Voeks, Jenifer H.; Hill, Allyson; Hibbert, Jacqueline M.; Gee, Beatrice E.

2015-01-01

Hypercoagulability in sickle cell disease (SCD) is associated with multiple SCD phenotypes, association with stroke risk has not been well described. We hypothesized that serum levels of biomarkers of coagulation activation correlate with high transcranial Doppler ultrasound velocity and decreases with blood transfusion therapy in SCD patients. Stored serum samples from subjects in the Stroke Prevention in Sickle Cell Anemia (STOP) trial were analyzed using ELISA and protein multiplexing techniques. 40 subjects from each treatment arm (Standard Care [SC] and Transfusion [Tx]) at three time points—baseline, study exit and one year post-trial and 10 each of age matched children with SCD but normal TCD (SNTCD) and with normal hemoglobin (HbAA) were analyzed. At baseline, median vWF, TAT and D-dimer levels were significantly higher among STOP subjects than either HbAA or SNTCD. At study exit, median hemoglobin level was significantly higher while median TCD velocity was significantly lower in Tx compared to SC subjects. Median vWF (409.6 vs. 542.9 μg/ml), TAT (24.8 vs. 40.0 ng/ml) and D-dimer (9.2 vs. 19.1 μg/ml) levels were also significantly lower in the Tx compared to the SC group at study exit. Blood levels of biomarkers coagulation activation/thrombin generation correlated positively with TCD velocity and negatively with number of blood transfusions. Biomarkers of coagulation activation/thrombin generation were significantly elevated in children with SCD, at high risk for stroke. Reduction in levels of these biomarkers correlated with reduction in stroke risk (lower TCD velocity), indicating a possible role for hypercoagulation in SCD associated stroke. PMID:26305570

Preventing stroke

MedlinePlus

... chap 65. Goldstein LB. Prevention and management of ischemic stroke. In: Mann DL, Zipes DP, Libby P, Bonow ... Editorial team. Related MedlinePlus Health Topics Hemorrhagic Stroke Ischemic Stroke Stroke Browse the Encyclopedia A.D.A.M., ...

Financial management of a large multisite randomized clinical trial.

PubMed

Sheffet, Alice J; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E; Longbottom, Mary E; Howard, Virginia J; Marler, John R; Brott, Thomas G

2014-08-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. © 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial.

PubMed

Al-Shahi Salman, Rustam; Dennis, Martin S; Murray, Gordon D; Innes, Karen; Drever, Jonathan; Dinsmore, Lynn; Williams, Carol; White, Philip M; Whiteley, William N; Sandercock, Peter A G; Sudlow, Cathie L M; Newby, David E; Sprigg, Nikola; Werring, David J

2018-03-05

For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Final results of RESTART will be analysed and disseminated in 2019. ISRCTN71907627 ( www.isrctn.com/ISRCTN71907627 ). Prospectively registered on 25 April 2013.

Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials

PubMed Central

Whiteley, William N; Adams, Harold P; Bath, Philip MW; Berge, Eivind; Sandset, Per Morten; Dennis, Martin; Murray, Gordon D; Wong, Ka-Sing Lawrence; Sandercock, Peter AG

2013-01-01

Summary Background Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke. Methods We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome “dead or dependent” in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis. Findings Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59–0·67) and for haemorrhagic events was 0·60 (0·55–0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events. Interpretation There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable to define a targeted approach to select the patients who would benefit from treatment with early anticoagulant therapy. We recommend that guidelines for routine or selective use of heparin in stroke should be revised. Funding MRC. PMID:23642343

Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials.

PubMed

Whiteley, William N; Adams, Harold P; Bath, Philip M W; Berge, Eivind; Sandset, Per Morten; Dennis, Martin; Murray, Gordon D; Wong, Ka-Sing Lawrence; Sandercock, Peter A G

2013-06-01

Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke. We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome "dead or dependent" in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis. Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59-0·67) and for haemorrhagic events was 0·60 (0·55-0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events. There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable to define a targeted approach to select the patients who would benefit from treatment with early anticoagulant therapy. We recommend that guidelines for routine or selective use of heparin in stroke should be revised. MRC. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis.

PubMed

Sundström, Johan; Arima, Hisatomi; Jackson, Rod; Turnbull, Fiona; Rahimi, Kazem; Chalmers, John; Woodward, Mark; Neal, Bruce

2015-02-03

Effects of blood pressure reduction in persons with grade 1 hypertension are unclear. To investigate whether pharmacologic blood pressure reduction prevents cardiovascular events and deaths in persons with grade 1 hypertension. Trials included in the BPLTTC (Blood Pressure Lowering Treatment Trialists' Collaboration) and trials identified from a previous review and electronic database searches. Patients without cardiovascular disease with blood pressures in the grade 1 hypertension range (140 to 159/90 to 99 mm Hg) who were randomly assigned to an active (antihypertensive drug or more intensive regimen) or control (placebo or less intensive regimen) blood pressure-lowering regimen. Individual-patient data from BPLTTC trials and aggregate data from other trials were extracted. Risk of bias was assessed for all trials. Individual-patient data involved 10 comparisons from trials where most patients had diabetes, and aggregate data involved 3 comparisons from trials of patients without diabetes. The average blood pressure reduction was about 3.6/2.4 mm Hg. Over 5 years, odds ratios were 0.86 (95% CI, 0.74 to 1.01) for total cardiovascular events, 0.72 (CI, 0.55 to 0.94) for strokes, 0.91 (CI, 0.74 to 1.12) for coronary events, 0.80 (CI, 0.57 to 1.12) for heart failure, 0.75 (CI, 0.57 to 0.98) for cardiovascular deaths, and 0.78 (CI, 0.67 to 0.92) for total deaths. Results were similar in secondary analyses. Withdrawal from treatment due to adverse effects was more common in the active groups. Blood pressure reductions and numbers of events were small. Blood pressure-lowering therapy is likely to prevent stroke and death in patients with uncomplicated grade 1 hypertension. Swedish Heart-Lung Foundation, Swedish Research Council, Australian Research Council, and National Health and Medical Research Council of Australia.

Personalized medicine and stroke prevention: where are we?

PubMed

Kim, Joosup; Thrift, Amanda G; Nelson, Mark R; Bladin, Christopher F; Cadilhac, Dominique A

2015-01-01

There are many recommended pharmacological and non-pharmacological therapies for the prevention of stroke, and an ongoing challenge is to improve their uptake. Personalized medicine is seen as a possible solution to this challenge. Although the use of genetic information to guide health care could be considered as the apex of personalized medicine, genetics is not yet routinely used to guide prevention of stroke. Currently personalized aspects of prevention of stroke include tailoring interventions based on global risk, the utilization of individualized management plans within a model of organized care, and patient education. In this review we discuss the progress made in these aspects of prevention of stroke and present a case study to illustrate the issues faced by health care providers and patients with stroke that could be overcome with a personalized approach to the prevention of stroke.

Vitamins E and C in the Prevention of Cardiovascular Disease in Men: The Physicians’ Health Study II Randomized Trial

PubMed Central

Sesso, Howard D.; Buring, Julie E.; Christen, William G.; Kurth, Tobias; Belanger, Charlene; MacFadyen, Jean; Bubes, Vadim; Manson, JoAnn E.; Glynn, Robert J.; Gaziano, J. Michael

2008-01-01

Context Basic and observational studies suggest vitamins E or C may reduce risk of cardiovascular disease (CVD). However, few long-term trials have evaluated men at initially low risk of CVD, and no previous trial in men has examined vitamin C alone in the prevention of CVD. Objective To test whether long-term vitamin E or C supplementation decreases risk of major cardiovascular events among men. Design, Setting, and Participants The Physicians’ Health Study II (PHS II) is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. We enrolled 14,641 U.S. male physicians initially aged ≥50 years, including 754 (5.1%) men with prevalent CVD at randomization. Intervention Individual supplements of 400 IU vitamin E every other day and 500 mg vitamin C daily. Main Outcome Measures A composite endpoint of major cardiovascular events (nonfatal myocardial infarction (MI), nonfatal stroke, and CVD death). Results During a mean follow-up of 8.0 years, there were 1,245 confirmed major cardiovascular events. Compared with placebo, vitamin E had no effect on the incidence of major cardiovascular events (both active and placebo vitamin E groups, 10.9 events per 1,000 person-years; hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.90–1.13; P=0.86), as well as total MI (HR, 0.90; 95% CI, 0.75–1.07; P=0.22), total stroke (HR, 1.07; 95% CI, 0.89–1.29; P=0.45), and cardiovascular mortality (HR, 1.07; 95% CI, 0.90–1.29; P=0.43). There was also no significant effect of vitamin C on major cardiovascular events (active and placebo vitamin E groups, 10.8 and 10.9 events per 1,000 person-years, respectively; HR, 0.99; 95% CI, 0.89–1.11; P=0.91), as well as total MI (HR, 1.04; 95% CI, 0.87–1.24; P=0.65), total stroke (HR, 0.89; 95% CI, 0.74–1.07; P=0.21), and cardiovascular mortality (HR, 1.02; 95% CI, 0.85–1.21; P=0.86). Neither vitamin E (HR, 1.07; 95% CI, 0.97–1.18; P=0.15) nor vitamin C (HR, 1.07; 95% CI, 0.97–1.18; P=0.16) had a significant effect on total mortality, but vitamin E was associated with an increased risk of hemorrhagic stroke (HR, 1.74; 95% CI, 1.04–2.91; P=0.036). Conclusions In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of CVD in middle-aged and older men. PMID:18997197

Green and black tea consumption and risk of stroke: a meta-analysis.

PubMed

Arab, Lenore; Liu, Weiqing; Elashoff, David

2009-05-01

Experimental models of stroke provide consistent evidence of smaller stroke volumes in animals ingesting tea components or tea extracts. To assess whether a similar association of black or green tea consumption with reduced risk is evident in human populations, we sought to identify and summarize all human clinical and observational data on tea and stroke. We searched PubMed and Web of Science for all studies on stroke and tea consumption in humans with original data, including estimation or measurement of tea consumption and outcomes of fatal or nonfatal stroke. Data from 9 studies involving 4378 strokes among 194 965 individuals were pooled. The main outcome was the occurrence of fatal or nonfatal stroke. We tested for heterogeneity and calculated the summary effect estimate associated with consumption of >or=3 cups of tea (green or black) per day using random-effects and fixed-effects models for the homogeneous studies. Publication bias was also evaluated. Regardless of their country of origin, individuals consuming >or=3 cups of tea per day had a 21% lower risk of stroke than those consuming <1 cup per day (absolute risk reduction, 0.79; CI, 0.73 to 0.85). The proportion of heterogeneity not explained by chance alone was 23.8%. Although a randomized clinical trial would be necessary to confirm the effect, this meta-analysis suggests that daily consumption of either green or black tea equaling 3 cups per day could prevent the onset of ischemic stroke.

Piracetam for acute ischaemic stroke.

PubMed

Ricci, Stefano; Celani, Maria Grazia; Cantisani, Teresa Anna; Righetti, Enrico

2012-09-12

Piracetam has neuroprotective and antithrombotic effects that may help to reduce death and disability in people with acute stroke. This is an update of a Cochrane Review first published in 1999, and previously updated in 2006 and 2009. To assess the effects of piracetam in acute, presumed ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched 15 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and ISI Science Citation Index (1981 to May 2011). We also contacted the manufacturer of piracetam to identify further published and unpublished studies. Randomised trials comparing piracetam with control, with at least mortality reported and entry to the trial within three days of stroke onset. Two review authors extracted data and assessed trial quality and this was checked by the other two review authors. We contacted study authors for missing information. We included three trials involving 1002 patients, with one trial contributing 93% of the data. Participants' ages ranged from 40 to 85 years, and both sexes were equally represented. Piracetam was associated with a statistically non-significant increase in death at one month (approximately 31% increase, 95% confidence interval 81% increase to 5% reduction). This trend was no longer apparent in the large trial after correction for imbalance in stroke severity. Limited data showed no difference between the treatment and control groups for functional outcome, dependence or proportion of patients dead or dependent. Adverse effects were not reported. There is some suggestion (but no statistically significant result) of an unfavourable effect of piracetam on early death, but this may have been caused by baseline differences in stroke severity in the trials. There is not enough evidence to assess the effect of piracetam on dependence.

Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses.

PubMed

Bellón, Juan Ángel; Moreno-Peral, Patricia; Motrico, Emma; Rodríguez-Morejón, Alberto; Fernández, Ana; Serrano-Blanco, Antoni; Zabaleta-del-Olmo, Edurne; Conejo-Cerón, Sonia

2015-07-01

To determine the effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression. Systematic review of systematic reviews and meta-analyses (SR/MA). We searched PubMed, PsycINFO, Cochrane Database of Systematic Reviews, OpenGrey, and PROSPERO from their inception until February 2014. Two reviewers independently evaluated the eligibility criteria of all SR/MA, abstracted data, and determined bias risk (AMSTAR). Twelve SR/MA (156 non-repeated trials and 56,158 participants) were included. Of these, 142 (91%) were randomized-controlled, 13 (8.3%) controlled trials, and 1 (0.6%) had no control group. Five SR/MA focused on children and adolescents, four on specific populations (women after childbirth, of low socioeconomic status, or unfavorable circumstances; patients with severe traumatic physical injuries or stroke) and three addressed the general population. Nine (75%) SR/MA concluded that interventions to prevent depression were effective. Of the 156 trials, 137 (87.8%) reported some kind of effect size calculation. Effect sizes were small in 45 (32.8%), medium in 26 (19.1%), and large in 25 (18.2%) trials; 41 (29.9%) trials were not effective. Of the 141 trials for which follow-up periods were available, only 34 (24.1%) exceeded 12 months. Psychological and/or educational interventions to prevent onset of episodes of depression were effective, although most had small or medium effect sizes. Copyright © 2014. Published by Elsevier Inc.

Factors Associated With Time to Site Activation, Randomization, and Enrollment Performance in a Stroke Prevention Trial.

PubMed

Demaerschalk, Bart M; Brown, Robert D; Roubin, Gary S; Howard, Virginia J; Cesko, Eldina; Barrett, Kevin M; Longbottom, Mary E; Voeks, Jenifer H; Chaturvedi, Seemant; Brott, Thomas G; Lal, Brajesh K; Meschia, James F; Howard, George

2017-09-01

Multicenter clinical trials attempt to select sites that can move rapidly to randomization and enroll sufficient numbers of patients. However, there are few assessments of the success of site selection. In the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials), we assess factors associated with the time between site selection and authorization to randomize, the time between authorization to randomize and the first randomization, and the average number of randomizations per site per month. Potential factors included characteristics of the site, specialty of the principal investigator, and site type. For 147 sites, the median time between site selection to authorization to randomize was 9.9 months (interquartile range, 7.7, 12.4), and factors associated with early site activation were not identified. The median time between authorization to randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5). Sites with authorization to randomize in only the carotid endarterectomy study were slower to randomize, and other factors examined were not significantly associated with time-to-randomization. The recruitment rate was 0.26 (95% confidence interval, 0.23-0.28) patients per site per month. By univariate analysis, factors associated with faster recruitment were authorization to randomize in both trials, principal investigator specialties of interventional radiology and cardiology, pre-trial reported performance >50 carotid angioplasty and stenting procedures per year, status in the top half of recruitment in the CREST trial, and classification as a private health facility. Participation in StrokeNet was associated with slower recruitment as compared with the non-StrokeNet sites. Overall, selection of sites with high enrollment rates will likely require customization to align the sites selected to the factor under study in the trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02089217. © 2017 American Heart Association, Inc.

Targeting aspirin in acute disabling ischemic stroke: an individual patient data meta-analysis of three large randomized trials.

PubMed

Thompson, Douglas D; Murray, Gordon D; Candelise, Livia; Chen, Zhengming; Sandercock, Peter A G; Whiteley, William N

2015-10-01

Aspirin is of moderate overall benefit for patients with acute disabling ischemic stroke. It is unclear whether functional outcome could be improved after stroke by targeting aspirin to patients with a high risk of recurrent thrombosis or a low risk of haemorrhage. We aimed to determine whether patients at higher risk of thrombotic events or poor functional outcome, or lower risk of major haemorrhage had a greater absolute risk reduction of poor functional outcome with aspirin than the average patient. We used data on individual ischemic stroke patients from three large trials of aspirin vs. placebo in acute ischemic stroke: the first International Stroke Trial (n = 18,372), the Chinese Acute Stroke Trial (n = 20,172) and the Multicentre Acute Stroke Trial (n = 622). We developed and evaluated clinical prediction models for the following: early thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis and pulmonary embolism); early haemorrhagic events (significant intracranial haemorrhage, major extracranial haemorrhage, or haemorrhagic transformation of an infarct); and late poor functional outcome. We calculated the absolute risk reduction of poor functional outcome (death or dependence) at final follow-up in: quartiles of early thrombotic risk; quartiles of early haemorrhagic risk; and deciles of poor functional outcome risk. Ischemic stroke patients who were older, had lower blood pressure, computerized tomography evidence of infarct or more severe deficits due to stroke had increased risk of thrombotic and haemorrhagic events and poor functional outcome. Prediction models built with all baseline variables (including onset to treatment time) discriminated weakly between patients with and without recurrent thrombotic events (area under the receiver operating characteristic curve 0·56, 95% CI:0·53-0·59) and haemorrhagic events (0·57, 0·52-0·64), though well between patients with and without poor functional outcome (0·77, 0·76-0·78) in the International Stroke Trial. We found no evidence that the net benefit of aspirin increased with increasing risk of thrombosis, haemorrhage or poor functional outcome in all three trials. Using simple clinical variables to target aspirin to patients after acute disabling stroke by risk of thrombosis, haemorrhage or poor functional outcome does not lead to greater net clinical benefit. We suggest future risk stratification schemes include new risk factors for thrombosis and intracranial haemorrhage. © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Cost-effectiveness of edoxaban versus rivaroxaban for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in the US

PubMed Central

Miller, Jeffrey D; Ye, Xin; Lenhart, Gregory M; Farr, Amanda M; Tran, Oth V; Kwong, W Jackie; Magnuson, Elizabeth A; Weintraub, William S

2016-01-01

Background Understanding the value of new anticoagulation therapies compared with existing therapies is of paramount importance in today’s cost-conscious and efficiency-driven health care environment. Edoxaban and rivaroxaban for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients with CHADS2 scores ≥2 have been evaluated in pivotal trials versus warfarin. The relative value of edoxaban versus rivaroxaban would be of interest to health care stakeholders and patients who prefer a once-daily treatment option for long-term stroke prevention in NVAF. Objective To evaluate the relative cost-effectiveness of two once-daily regimens of novel oral anticoagulation therapy – edoxaban (60 mg/30 mg dose-reduced) versus rivaroxaban (20 mg/15 mg dose-reduced) – for stroke prevention in NVAF patients from a US health-plan perspective. Materials and methods A Markov model simulated lifetime risk and treatment of stroke, systemic embolism, major bleeding, clinically relevant nonmajor bleeding, myocardial infarction, and death in NVAF patients treated with edoxaban or rivaroxaban. Efficacy and safety data were derived from a network meta-analysis that utilized data from patients enrolled in ENGAGE AF-TIMI 48 and ROCKET-AF. Health care cost and utility data were obtained from published sources. Incremental cost-effectiveness ratios of $150,000 per quality-adjusted life year (QALY) gained were used as thresholds for “highly cost-effective”, “cost-effective”, and “not cost-effective” treatment options, respectively, as per American Heart Association/American College of Cardiology guidelines. Results Edoxaban was dominant relative to rivaroxaban, such that it was associated with lower total health care costs and better effectiveness in terms of QALYs in the base-case analysis. Results were supported by probabilistic sensitivity analyses that showed edoxaban as either dominant or a highly cost-effective alternative (incremental cost-effectiveness ratio <$50,000) to rivaroxaban in 88.4% of 10,000 simulations. Conclusion Results of this study showed that the once-daily edoxaban (60 mg/30 mg dose-reduced) regimen is a cost-saving or highly cost-effective treatment relative to rivaroxaban (20 mg/15 mg dose-reduced) for stroke prevention in NVAF patients with CHADS2 ≥2. PMID:27284259

Protocol for a prospective collaborative systematic review and meta-analysis of individual patient data from randomized controlled trials of vasoactive drugs in acute stroke: The Blood pressure in Acute Stroke Collaboration, stage-3.

PubMed

Sandset, Else Charlotte; Sanossian, Nerses; Woodhouse, Lisa J; Anderson, Craig; Berge, Eivind; Lees, Kennedy R; Potter, John F; Robinson, Thompson G; Sprigg, Nikola; Wardlaw, Joanna M; Bath, Philip M

2018-01-01

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains particularly for ischemic stroke. The "Blood pressure in Acute Stroke Collaboration" commenced in the mid-1990s focussing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, Blood pressure in Acute Stroke Collaboration planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, including both intracerebral hemorrhage and ischemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on hemodynamic variables. Methods and design Individual patient data from randomized controlled trials of blood pressure management in participants with ischemic stroke and/or intracerebral hemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 h), acute (<48 h), and sub-acute (<168 h) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in pre-specified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, hemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration.

Stroke unit care benefits patients with intracerebral hemorrhage: systematic review and meta-analysis.

PubMed

Langhorne, Peter; Fearon, Patricia; Ronning, Ole M; Kaste, Markku; Palomaki, Heikki; Vemmos, Kostos; Kalra, Lalit; Indredavik, Bent; Blomstrand, Christian; Rodgers, Helen; Dennis, Martin S; Al-Shahi Salman, Rustam

2013-11-01

Patients with any type of stroke managed in organized inpatient (stroke unit) care are more likely to survive, return home, and regain independence. However, it is uncertain whether these benefits apply equally to patients with intracerebral hemorrhage and ischemic stroke. We conducted a secondary analysis of a systematic review of controlled clinical trials comparing stroke unit care with general ward care, including only trials published after 1990 that could separately report outcomes for patients with intracerebral hemorrhage and ischemic stroke. We performed random-effects meta-analyses and tested for subgroup interactions by stroke type. We identified 13 trials (3570 patients) of modern stroke unit care that recruited patients with intracerebral hemorrhage and ischemic stroke, of which 8 trials provided data on 2657 patients. Stroke unit care reduced death or dependency (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.471-0.92; P=0.0009; I2=60%) with no difference in benefits for patients with intracerebral hemorrhage (RR, 0.79; 95% CI, 0.61-1.00) than patients with ischemic stroke (RR, 0.82; 95% CI, 0.70-0.97; Pinteraction=0.77). Stroke unit care reduced death (RR, 0.79; 95% CI, 0.64-0.97; P=0.02; I2=49%) to a greater extent for patients with intracerebral hemorrhage (RR, 0.73; 95% CI, 0.54-0.97) than patients with ischemic stroke (RR, 0.82; 95%, CI 0.61-1.09), but this difference was not statistically significant (Pinteraction=0.58). Patients with intracerebral hemorrhage seem to benefit at least as much as patients with ischemic stroke from organized inpatient (stroke unit) care.

Developing a culturally-tailored stroke prevention walking program for Korean immigrant seniors: A focus group study

PubMed Central

Kwon, Ivy; Chang, Emiley; Araiza, Daniel; Thorpe, Carol Lee; Sarkisian, Catherine A.

2016-01-01

Background Physical inactivity is a major risk factor for stroke. Korean immigrant seniors are one of the most sedentary ethnic groups in the United States. Objectives To gain better understanding of (i) Beliefs and knowledge about stroke; (ii) Attitudes about walking for stroke prevention; and (iii) Barriers and facilitators to walking among Korean seniors for the cultural tailoring of a stroke prevention walking program. Design An explorative study using focus group data. Twenty-nine Korean immigrant seniors (64–90 years of age) who had been told by a doctor at least once that their blood pressure was elevated participated in 3 focus groups. Each focus group consisted of 8–11 participants. Methods Focus group audio tapes were transcribed and analyzed using standard content analysis methods. Results Participants identified physical and psychological imbalances (e.g., too much work and stress) as the primary causes of stroke. Restoring ‘balance’ was identified as a powerful means of stroke prevention. A subset of participants expressed that prevention may be beyond human control. Overall, participants acknowledged the importance of walking for stroke prevention, but described barriers such as lack of personal motivation and unsafe environment. Many participants believed that providing opportunities for socialization while walking and combining walking with health information sessions would facilitate participation in and maintenance of a walking program. Conclusions Korean immigrant seniors believe strongly that imbalance is a primary cause of stroke. Restoring balance as a way to prevent stroke is culturally special among Koreans and provides a conceptual base in culturally tailoring our stroke prevention walking intervention for Korean immigrant seniors. Implications for practice A stroke prevention walking program for Korean immigrant seniors may have greater impact by addressing beliefs about stroke causes and prevention such as physical and psychological imbalances and the importance of maintaining emotional wellbeing. PMID:26778221

Developing a culturally tailored stroke prevention walking programme for Korean immigrant seniors: a focus group study.

PubMed

Choi, Sarah E; Kwon, Ivy; Chang, Emiley; Araiza, Daniel; Thorpe, Carol Lee; Sarkisian, Catherine A

2016-12-01

To gain better understanding of (i) beliefs and knowledge about stroke; (ii) attitudes about walking for stroke prevention; and (iii) barriers and facilitators to walking among Korean seniors for the cultural tailoring of a stroke prevention walking programme. Physical inactivity is a major risk factor for stroke. Korean immigrant seniors are one of the most sedentary ethnic groups in the United States. An explorative study using focus group data. Twenty-nine Korean immigrant seniors (64-90 years of age) who had been told by a doctor at least once that their blood pressure was elevated participated in 3 focus groups. Each focus group consisted of 8-11 participants. Focus group audiotapes were transcribed and analysed using standard content analysis methods. Participants identified physical and psychological imbalances (e.g. too much work and stress) as the primary causes of stroke. Restoring 'balance' was identified as a powerful means of stroke prevention. A subset of participants expressed that prevention may be beyond human control. Overall, participants acknowledged the importance of walking for stroke prevention, but described barriers such as lack of personal motivation and unsafe environment. Many participants believed that providing opportunities for socialisation while walking and combining walking with health information sessions would facilitate participation in and maintenance of a walking programme. Korean immigrant seniors believe strongly that imbalance is a primary cause of stroke. Restoring balance as a way to prevent stroke is culturally special among Koreans and provides a conceptual base in culturally tailoring our stroke prevention walking intervention for Korean immigrant seniors. A stroke prevention walking programme for Korean immigrant seniors may have greater impact by addressing beliefs about stroke causes and prevention such as physical and psychological imbalances and the importance of maintaining emotional well-being. © 2016 John Wiley & Sons Ltd.

Early blood pressure lowering treatment in acute stroke. Ordinal analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial (SCAST).

PubMed

Jusufovic, Mirza; Sandset, Else Charlotte; Bath, Philip M; Berge, Eivind

2016-08-01

Early blood pressure-lowering treatment appears to be beneficial in patients with acute intracerebral haemorrhage and potentially in ischaemic stroke. We used a new method for analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial to see if the effect was dependent on the timing of treatment. Scandinavian Candesartan Acute Stroke Trial was a randomized controlled and placebo-controlled trial of candesartan within 30 h of ischaemic or haemorrhagic stroke. Of 2029 patients, 231 (11.4%) had a vascular event (vascular death, nonfatal stroke or nonfatal myocardial infarction) during the first 6 months. The modified Rankin Scale (mRS) score following a vascular event was used to categorize vascular events in order of severity: no event (n = 1798), minor (mRS 0-2, n = 59), moderately severe (mRS 3-4, n = 57) and major event (mRS 5-6, n = 115). We used ordinal logistic regression for analysis and adjusted for predefined prognostic variables. Candesartan had no overall effect on vascular events (adjusted common odds ratio 1.11, 95% confidence interval 0.84-1.47, P = 0.48), and the effects were the same in ischaemic and haemorrhagic stroke. Among the patients treated within 6 h, the adjusted common odds ratio for vascular events was 0.37, 95% confidence interval 0.16-0.84, P = 0.02, and there was no heterogeneity of effect between ischaemic and haemorrhagic strokes. Ordinal analysis of vascular events showed no overall effect of candesartan in the subacute phase of stroke. The effect of treatment given within 6 h of stroke onset appears promising, and will be addressed in ongoing trials. Ordinal analysis of vascular events is feasible and can be used in future trials.

Ticagrelor for the treatment of atherosclerotic disease: insights from the PARTHENON clinical development program.

PubMed

Held, Peter; Himmelmann, Anders; Ditmarsch, Marc

2016-07-01

Ticagrelor (P2Y12 receptor antagonist) is presently indicated for preventing atherothrombotic events in patients with acute coronary syndrome and patients with a history of myocardial infarction. The PARTHENON clinical development program comprises five randomized, controlled, cardiovascular, indication-seeking outcome studies, aiming to evaluate ticagrelor across the spectrum of patients with atherothrombotic disease. Results of two large-scale trials support a benefit for ticagrelor in patients with acute coronary syndrome (PLATO; ClinicalTrials.gov: NCT00391872) and in patients with a history of myocardial infarction (PEGASUS-TIMI 54; ClinicalTrials.gov: NCT01225562). Ongoing trials will provide information on the efficacy and safety of ticagrelor in patients with acute ischemic stroke or transient ischemic attack (SOCRATES; ClinicalTrials.gov: NCT01994720), peripheral artery disease (EUCLID; ClinicalTrials.gov: NCT01732822) and coronary artery disease in patients with Type 2 diabetes mellitus (THEMIS: ClinicalTrials.gov: NCT01991795).

The incidence of ischemic stroke in chronic heart failure: a meta-analysis.

PubMed

Witt, Brandi J; Gami, Apoor S; Ballman, Karla V; Brown, Robert D; Meverden, Ryan A; Jacobsen, Stephen J; Roger, Véronique L

2007-08-01

There is marked variability in the reported stroke rates among persons with heart failure (HF). We performed a meta-analysis to provide summary estimates of the stroke rate in HF and to explain heterogeneity in the existing literature. We will summarize the ischemic stroke rate at various time points during follow-up among adults with chronic heart failure. A systematic review of the electronic literature in Medline and PubMed as well as hand searching of the reference lists of identified articles and of the meeting abstracts for the 1995-2004 American College of Cardiology and American Heart Association scientific sessions was performed to identify qualifying studies. Articles were included if they included a population with chronic HF and reported the number (or percent) of persons with HF who experienced an ischemic stroke during follow-up. Studies were excluded if the study population included > or = 50% of persons with acute (postmyocardial infarction) HF, or if > or = 50% of the study population required artificial support with a ventricular assist device or parenteral inotropic medications. Case reports, case series, and nonoriginal research articles were not included. Determination of study eligibility and data extraction were conducted by 2 independent reviewers using standardized forms. Results are reported as stroke rate per 1000 cases of HF, with 95% Poisson confidence intervals. Pooled estimates of the stroke rate were calculated with fixed and random effects models. Heterogeneity was explored according to a priori specified subgroup analyses. Overall, 26 studies met inclusion criteria. Eighteen of every 1000 persons suffered a stroke during the first year after the diagnosis of HF. The stroke rate increased to a maximum of 47.4 per 1000 at 5 years. Studies with fewer women, those conducted in 1990 or earlier, and cohort studies reported higher stroke rates than studies with more women, those conducted after 1990, and clinical trials. Stroke is an important complication among persons with HF. Variability among reported stroke rates can be explained in part by differences in study design, patient population, and HF standards of care at the time of the study. Despite the heterogeneity in reported stroke rates, this meta-analysis shows that stroke prevention in HF represents an opportunity to prevent morbidity and save many lives in this highly fatal disease.

Lifestyle and stroke risk: a review.

PubMed

Galimanis, Aekaterini; Mono, Marie-Luise; Arnold, Marcel; Nedeltchev, Krassen; Mattle, Heinrich P

2009-02-01

In recent years, many epidemiological studies have given new insights into old and new lifestyle factors that influence the risk of cerebrovascular events. In this review, we refer to the most important articles to highlight recent advances, especially those important for stroke prevention. This review focuses on the most recent studies that show the association of environmental factors, nutrition, alcohol, tobacco, education, lifestyle and behavior with the risk of vascular disease, including ischemic stroke and cerebral hemorrhage. The link between air pollution and stroke risk has become evident. Low education levels and depression are established as risk factors. This is also true for heavy alcohol consumption, although moderate drinking may be protective. Active and passive smoking are independent risk factors, and a smoking ban in public places has already reduced cardiovascular events in the short term. Physical activity reduces stroke risk; overweight increases it. However, clinical trials to assess the effect of weight reduction on stroke risk are still lacking. Fruits, vegetables, fish, fibers, low-fat dairy products, potassium and low sodium consumption are known and recommended to reduce cardiovascular risk. Data on omega 3 fatty acid, folic acid and B vitamins are inconsistent, and antioxidants are not recommended. Stroke can be substantially reduced by an active lifestyle, cessation of smoking and a healthy diet. Both public and professional education should promote the awareness that a healthy lifestyle and nutrition have the potential to reduce the burden of stroke.

A cross-laboratory preclinical study on the effectiveness of interleukin-1 receptor antagonist in stroke

PubMed Central

Maysami, Samaneh; Wong, Raymond; Pradillo, Jesus M; Denes, Adam; Dhungana, Hiramani; Malm, Tarja; Koistinaho, Jari; Orset, Cyrille; Rahman, Mahbubur; Rubio, Marina; Schwaninger, Markus; Vivien, Denis; Bath, Philip M; Rothwell, Nancy J

2015-01-01

Stroke represents a global challenge and is a leading cause of permanent disability worldwide. Despite much effort, translation of research findings to clinical benefit has not yet been successful. Failure of neuroprotection trials is considered, in part, due to the low quality of preclinical studies, low level of reproducibility across different laboratories and that stroke co-morbidities have not been fully considered in experimental models. More rigorous testing of new drug candidates in different experimental models of stroke and initiation of preclinical cross-laboratory studies have been suggested as ways to improve translation. However, to our knowledge, no drugs currently in clinical stroke trials have been investigated in preclinical cross-laboratory studies. The cytokine interleukin 1 is a key mediator of neuronal injury, and the naturally occurring interleukin 1 receptor antagonist has been reported as beneficial in experimental studies of stroke. In the present paper, we report on a preclinical cross-laboratory stroke trial designed to investigate the efficacy of interleukin 1 receptor antagonist in different research laboratories across Europe. Our results strongly support the therapeutic potential of interleukin 1 receptor antagonist in experimental stroke and provide further evidence that interleukin 1 receptor antagonist should be evaluated in more extensive clinical stroke trials. PMID:26661169

Routine low-dose continuous or nocturnal oxygen for people with acute stroke: three-arm Stroke Oxygen Supplementation RCT.

PubMed

Roffe, Christine; Nevatte, Tracy; Bishop, Jon; Sim, Julius; Penaloza, Cristina; Jowett, Susan; Ives, Natalie; Gray, Richard; Ferdinand, Phillip; Muddegowda, Girish

2018-03-01

Stroke is a major cause of death and disability worldwide. Hypoxia is common after stroke and is associated with worse outcomes. Oxygen supplementation could prevent hypoxia and secondary brain damage. (1) To assess whether or not routine low-dose oxygen supplementation in patients with acute stroke improves outcome compared with no oxygen; and (2) to assess whether or not oxygen given at night only, when oxygen saturation is most likely to be low, is more effective than continuous supplementation. Multicentre, prospective, randomised, open, blinded-end point trial. Secondary care hospitals with acute stroke wards. Adult stroke patients within 24 hours of hospital admission and 48 hours of stroke onset, without definite indications for or contraindications to oxygen or a life-threatening condition other than stroke. Allocated by web-based minimised randomisation to: (1) continuous oxygen: oxygen via nasal cannula continuously (day and night) for 72 hours after randomisation at a flow rate of 3 l/minute if baseline oxygen saturation was ≤ 93% or 2 l/minute if > 93%; (2) nocturnal oxygen: oxygen via nasal cannula overnight (21:00-07:00) for three consecutive nights. The flow rate was the same as the continuous oxygen group; and (3) control: no routine oxygen supplementation unless required for reasons other than stroke. Primary outcome: disability assessed by the modified Rankin Scale (mRS) at 3 months by postal questionnaire (participant aware, assessor blinded). Secondary outcomes at 7 days: neurological improvement, National Institutes of Health Stroke Scale (NIHSS), mortality, and the highest and lowest oxygen saturations within the first 72 hours. Secondary outcomes at 3, 6, and 12 months: mortality, independence, current living arrangements, Barthel Index, quality of life (European Quality of Life-5 Dimensions, three levels) and Nottingham Extended Activities of Daily Living scale by postal questionnaire. In total, 8003 patients were recruited between 24 April 2008 and 17 June 2013 from 136 hospitals in the UK [continuous, n  = 2668; nocturnal, n  = 2667; control, n  = 2668; mean age 72 years (standard deviation 13 years); 4398 (55%) males]. All prognostic factors and baseline characteristics were well matched across the groups. Eighty-two per cent had ischaemic strokes. At baseline the median Glasgow Coma Scale score was 15 (interquartile range 15-15) and the mean and median NIHSS scores were 7 and 5 (range 0-34), respectively. The mean oxygen saturation at randomisation was 96.6% in the continuous and nocturnal oxygen groups and 96.7% in the control group. Primary outcome: oxygen supplementation did not reduce disability in either the continuous or the nocturnal oxygen groups. The unadjusted odds ratio for a better outcome (lower mRS) was 0.97 [95% confidence interval (CI) 0.89 to 1.05; p  = 0.5] for the combined oxygen groups (both continuous and nocturnal together) ( n  = 5152) versus the control ( n  = 2567) and 1.03 (95% CI 0.93 to 1.13; p  = 0.6) for continuous versus nocturnal oxygen. Secondary outcomes: oxygen supplementation significantly increased oxygen saturation, but did not affect any of the other secondary outcomes. Severely hypoxic patients were not included. Routine low-dose oxygen supplementation in stroke patients who are not severely hypoxic is safe, but does not improve outcome after stroke. To investigate the causes of hypoxia and develop methods of prevention. Current Controlled Trials ISRCTN52416964 and European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2006-003479-11. This project was funded by the National Institute for Health Research (NIHR) Research for Patient Benefit and Health Technology Assessment programmes and will be published in full in Health Technology Assessment ; Vol. 22, No. 14. See the NIHR Journals Library website for further project information.

Exploring recruitment issues in stroke research: a qualitative study of nurse researchers' experiences.

PubMed

Boxall, Leigh; Hemsley, Anthony; White, Nicola

2016-05-01

To explore the practice of experienced stroke nurse researchers to understand the issues they face in recruiting participants. Participant recruitment is one of the greatest challenges in conducting clinical research, with many trials failing due to recruitment problems. Stroke research is a particularly difficult area in which to recruit; however various strategies can improve participation. Analysis revealed three main types of problems for recruiting participants to stroke research: those related to patients, those related to the nurse researcher, and those related to the study itself. Impairments affecting capacity to consent, the acute recruitment time frame of most stroke trials, paternalism by nurse researchers, and low public awareness were especially pertinent. The disabling nature of a stroke, which often includes functional and cognitive impairments, and the acute stage of illness at which patients are appropriate for many trials, make recruiting patients particularly complex and challenging. An awareness of the issues surrounding the recruitment of stroke patients may help researchers in designing and conducting trials. Future work is needed to address the complexities of obtaining informed consent when patient capacity is compromised.

The effect of electrical stimulation in combination with Bobath techniques in the prevention of shoulder subluxation in acute stroke patients.

PubMed

Fil, Ayla; Armutlu, Kadriye; Atay, Ahmet Ozgur; Kerimoglu, Ulku; Elibol, Bulent

2011-01-01

To examine the efficiency of electrical stimulation in combination with Bobath techniques in the prevention of inferior and anterior shoulder subluxation in acute stroke patients. A prospective randomized controlled trial. Intensive care unit and inpatient clinics of neurology in a university hospital. Forty-eight patients with acute stroke, divided equally into control and study groups. Subjects in both groups were treated in accordance with the Bobath concept during the early hospitalization period. In addition to Bobath techniques, electrical stimulation was also applied to the supraspinatus muscle, mid and posterior portions of the deltoid muscle of patients in the study group. Two radiological methods were used to measure the horizontal, vertical and total asymmetry and vertical distance values of the shoulder joint. Motor functions of the arm were evaluated with the Motor Assessment Scale. The hospitalization period was 12.62 ± 2.24 days for the control group and 11.66 ± 1.88 days for the study group. Shoulder subluxation occurred in 9 (37.5%) subjects in the control group, whereas it was not observed in the study group. All shoulder joint displacement values were higher in the control group than in the study group (horizontal asymmetry P = 0.0001, vertical asymmetry P = 0.0001, total asymmetry P = 0.0001, vertical range P = 0.002). Application of electrical stimulation combined with the Bobath approach proved to be efficient in preventing inferior and anterior shoulder subluxation in the acute stages of stroke.

Global Burden of Stroke.

PubMed

Feigin, Valery L; Norrving, Bo; Mensah, George A

2017-02-03

On the basis of the GBD (Global Burden of Disease) 2013 Study, this article provides an overview of the global, regional, and country-specific burden of stroke by sex and age groups, including trends in stroke burden from 1990 to 2013, and outlines recommended measures to reduce stroke burden. It shows that although stroke incidence, prevalence, mortality, and disability-adjusted life-years rates tend to decline from 1990 to 2013, the overall stroke burden in terms of absolute number of people affected by, or who remained disabled from, stroke has increased across the globe in both men and women of all ages. This provides a strong argument that "business as usual" for primary stroke prevention is not sufficiently effective. Although prevention of stroke is a complex medical and political issue, there is strong evidence that substantial prevention of stroke is feasible in practice. The need to scale-up the primary prevention actions is urgent. © 2017 American Heart Association, Inc.

Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial.

PubMed

Kalra, Lalit; Irshad, Saddif; Hodsoll, John; Simpson, Matthew; Gulliford, Martin; Smithard, David; Patel, Anita; Rebollo-Mesa, Irene

2015-11-07

Post-stroke pneumonia is associated with increased mortality and poor functional outcomes. This study assessed the effectiveness of antibiotic prophylaxis for reducing pneumonia in patients with dysphagia after acute stroke. We did a prospective, multicentre, cluster-randomised, open-label controlled trial with masked endpoint assessment of patients older than 18 years with dysphagia after new stroke recruited from 48 stroke units in the UK, accredited and included in the UK National Stroke Audit. We excluded patients with contraindications to antibiotics, pre-existing dysphagia, or known infections, or who were not expected to survive beyond 14 days. We randomly assigned the units (1:1) by computer to give either prophylactic antibiotics for 7 days plus standard stroke unit care or standard stroke unit care only to patients clustered in the units within 48 h of stroke onset. We did the randomisation with minimisation to stratify for number of admissions and access to specialist care. Patient and staff who did the assessments and analyses were masked to stroke unit allocation. The primary outcome was post-stroke pneumonia in the first 14 days, assessed with both a criteria-based, hierarchical algorithm and by physician diagnosis in the intention-to-treat population. Safety was also analysed by intention to treat. This trial is closed to new participants and is registered with isrctn.com, number ISRCTN37118456. Between April 21, 2008, and May 17, 2014, we randomly assigned 48 stroke units (and 1224 patients clustered within the units) to the two treatment groups: 24 to antibiotics and 24 to standard care alone (control). 11 units and seven patients withdrew after randomisation before 14 days, leaving 1217 patients in 37 units for the intention-to-treat analysis (615 patients in the antibiotics group, 602 in control). Prophylactic antibiotics did not affect the incidence of algorithm-defined post-stroke pneumonia (71 [13%] of 564 patients in antibiotics group vs 52 [10%] of 524 in control group; marginal adjusted odds ratio [OR] 1·21 [95% CI 0·71-2·08], p=0·489, intraclass correlation coefficient [ICC] 0·06 [95% CI 0·02-0·17]. Algorithm-defined post-stroke pneumonia could not be established in 129 (10%) patients because of missing data. Additionally, we noted no differences in physician-diagnosed post-stroke pneumonia between groups (101 [16%] of 615 patients vs 91 [15%] of 602, adjusted OR 1·01 [95% CI 0·61-1·68], p=0·957, ICC 0·08 [95% CI 0·03-0·21]). The most common adverse events were infections unrelated to post-stroke pneumonia (mainly urinary tract infections), which were less frequent in the antibiotics group (22 [4%] of 615 vs 45 [7%] of 602; OR 0·55 [0·32-0·92], p=0·02). Diarrhoea positive for Clostridium difficile occurred in two patients (<1%) in the antibiotics group and four (<1%) in the control group, and meticillin-resistant Staphylococcus aureus colonisation occurred in 11 patients (2%) in the antibiotics group and 14 (2%) in the control group. Antibiotic prophylaxis cannot be recommended for prevention of post-stroke pneumonia in patients with dysphagia after stroke managed in stroke units. UK National Institute for Health Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aspirin for primary prevention of cardiovascular and all-cause mortality events in diabetes: updated meta-analysis of randomized controlled trials.

PubMed

Kunutsor, S K; Seidu, S; Khunti, K

2017-03-01

To evaluate the benefits and harms of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in people with diabetes by conducting a systematic review and meta-analysis. Randomized controlled trials of aspirin compared with placebo (or no treatment) in people with diabetes with no history of cardiovascular disease were identified from MEDLINE, EMBASE, Web of Science, the Cochrane Library and a manual search of bibliographies to November 2015. Study-specific relative risks with 95% CIs were aggregated using random effects models. A total of 10 randomized trials were included in the review. There was a significant reduction in risk of major adverse cardiovascular events: relative risk of 0.90 (95% CI 0.81-0.99) in groups taking aspirin compared with placebo or no treatment. Limited subgroup analyses suggested that the effect of aspirin on major adverse cardiovascular events differed by baseline cardiovascular disease risk, medication compliance and sex (P for interaction for all > 0.05).There was no significant reduction in the risk of myocardial infarction, coronary heart disease, stroke, cardiovascular mortality or all-cause mortality. Aspirin significantly reduced the risk of myocardial infarction for a treatment duration of ≤ 5 years. There were differences in the effect of aspirin by dosage and treatment duration on overall stroke outcomes (P for interaction for all < 0.05). There was an increase in risk of major or gastrointestinal bleeding events, but estimates were imprecise and not significant. The emerging data do not clearly support guidelines that encourage the use of aspirin for the primary prevention of cardiovascular disease in adults with diabetes who are at increased cardiovascular disease risk. © 2016 Diabetes UK.

Efficacy and Safety of Individualized Coaching After Stroke: the LAST Study (Life After Stroke): A Pragmatic Randomized Controlled Trial.

PubMed

Askim, Torunn; Langhammer, Birgitta; Ihle-Hansen, Hege; Gunnes, Mari; Lydersen, Stian; Indredavik, Bent

2018-02-01

The evidence for interventions to prevent functional decline in the long term after stroke is lacking. The aim of this trial was to evaluate the efficacy and safety of an 18-month follow-up program of individualized regular coaching on physical activity and exercise. This was a multicentre, pragmatic, single-blinded, randomized controlled trial. Adults (age ≥18 years) with first-ever or recurrent stroke, community dwelling, with modified Rankin Scale <5, and no serious comorbidities were included 10 to 16 weeks poststroke. The intervention group received individualized regular coaching on physical activity and exercise every month for 18 consecutive months. The control group received standard care. Primary outcome was the Motor Assessment Scale at end of intervention (18-month follow-up). Secondary measures were Barthel index, modified Rankin Scale, item 14 from Berg Balance Scale, Timed Up and Go test, gait speed, 6-minute walk test, and Stroke Impact Scale. Other outcomes were adverse events and compliance to the intervention assessed by training diaries and the International Physical Activity Questionnaire. Three hundred and eighty consenting participants were randomly assigned to individualized coaching (n=186) or standard care (n=194). The mean estimated difference on Motor Assessment Scale in favor of control group was -0.70 points (95% confidence interval, -2.80, 1.39), P =0.512. There were no differences between the groups on Barthel index, modified Rankin Scale, or Berg Balance Scale. The frequency of adverse events was low in both groups. Results from International Physical Activity Questionnaire and training diaries showed increased activity levels but low intensity of the exercise in the intervention group. The regular individualized coaching did not improve maintenance of motor function or the secondary outcomes compared with standard care. The intervention should be regarded as safe. Despite the neutral results, the health costs related to the intervention should be investigated. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01467206. © 2017 American Heart Association, Inc.

Metabolites of Glutamate Metabolism Are Associated With Incident Cardiovascular Events in the PREDIMED PREvención con DIeta MEDiterránea (PREDIMED) Trial.

PubMed

Zheng, Yan; Hu, Frank B; Ruiz-Canela, Miguel; Clish, Clary B; Dennis, Courtney; Salas-Salvado, Jordi; Hruby, Adela; Liang, Liming; Toledo, Estefania; Corella, Dolores; Ros, Emilio; Fitó, Montserrat; Gómez-Gracia, Enrique; Arós, Fernando; Fiol, Miquel; Lapetra, José; Serra-Majem, Lluis; Estruch, Ramón; Martínez-González, Miguel A

2016-09-15

Glutamate metabolism may play a role in the pathophysiology of cardiometabolic disorders. However, there is limited evidence of an association between glutamate-related metabolites and, moreover, changes in these metabolites, and risk of cardiovascular disease (CVD). Plasma levels of glutamate and glutamine were measured at baseline and 1-year follow-up in a case-cohort study including 980 participants (mean age 68 years; 46% male) from the PREvención con DIeta MEDiterránea (PREDIMED) randomized trial, which assessed a Mediterranean diet intervention in the primary prevention of CVD. During median 4.8 years of follow-up, there were 229 incident CVD events (nonfatal stroke, nonfatal myocardial infarction, or CVD death). In fully adjusted models, per 1-SD, baseline glutamate was associated with 43% (95% CI: 16% to 76%) and 81% (39% to 137%) increased risk of composite CVD and stroke alone, respectively, and baseline glutamine-to-glutamate ratio with 25% (6% to 40%) and 44% (25% to 58%) decreased risk of composite CVD and stroke alone, respectively. Associations appeared linear for stroke (both Plinear trend≤0.005). Among participants with high baseline glutamate, the interventions lowered CVD risk by 37% compared to the control diet; the intervention effects were not significant when baseline glutamate was low (Pinteraction=0.02). No significant effect of the intervention on year-1 changes in metabolites was observed, and no effect of changes themselves on CVD risk was apparent. Baseline glutamate was associated with increased CVD risk, particularly stroke, and glutamine-to-glutamate ratio was associated with decreased risk. Participants with high glutamate levels may obtain greater benefits from the Mediterranean diet than those with low levels. URL: www.controlled-trials.com. Unique identifier: ISRCTN 35739639. © 2016 The Authors and The Broad Institute. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

On-Treatment Outcomes in Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights From ROCKET AF.

PubMed

Fordyce, Christopher B; Hellkamp, Anne S; Lokhnygina, Yuliya; Lindner, Samuel M; Piccini, Jonathan P; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Fox, Keith A A; Mahaffey, Kenneth W; Nessel, Christopher C; Singer, Daniel E; Patel, Manesh R

2016-07-05

Despite rapid clinical adoption of novel anticoagulants, it is unknown whether outcomes differ among patients with worsening renal function (WRF) taking these new drugs compared with warfarin. We aimed to determine whether the primary efficacy (stroke or systemic embolism) and safety (major bleeding and nonmajor clinically relevant bleeding) end points from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial) differed among participants with WRF taking rivaroxaban and those taking warfarin. After excluding patients without at least 1 follow-up creatinine measurement (n=1624), we included all remaining patients (n=12 612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. On-treatment WRF (a decrease of >20% from screening creatinine clearance measurement at any time point during the study) was evaluated as a time-dependent covariate in Cox proportional hazards models. Baseline characteristics were generally similar between patients with stable renal function (n=9292) and WRF (n=3320). Rates of stroke or systemic embolism, myocardial infarction, and bleeding were also similar, but WRF patients experienced a higher incidence of vascular death versus stable renal function (2.21 versus 1.41 events per 100 patient-years; P=0.026). WRF patients who were randomized to receive rivaroxaban had a reduction in stroke or systemic embolism compared with those taking warfarin (1.54 versus 3.25 events per 100 patient-years) that was not seen in patients with stable renal function who were randomized to receive rivaroxaban (P=0.050 for interaction). There was no difference in major or nonmajor clinically relevant bleeding among WRF patients randomized to warfarin versus rivaroxaban. Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and systemic embolism compared with warfarin, without an increase in the composite bleeding end point. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767. © 2016 American Heart Association, Inc.

Oral anticoagulant re-initiation following intracerebral hemorrhage in non-valvular atrial fibrillation: Global survey of the practices of neurologists, neurosurgeons and thrombosis experts.

PubMed

Xu, Yan; Shoamanesh, Ashkan; Schulman, Sam; Dowlatshahi, Dar; Al-Shahi Salman, Rustam; Moldovan, Ioana Doina; Wells, Philip Stephen; AlKherayf, Fahad

2018-01-01

While oral anticoagulants (OACs) are highly effective for ischemic stroke prevention in atrial fibrillation, intracerebral hemorrhage (ICH) remains the most feared complication of OAC. Clinical controversy remains regarding OAC resumption and its timing for ICH survivors with atrial fibrillation because the balance between risks and benefits has not been investigated in randomized trials. To survey the practice of stroke neurologists, thrombosis experts and neurosurgeons on OAC re-initiation following OAC-associated ICH. An online survey was distributed to members of the International Society for Thrombosis and Haemostasis, Canadian Stroke Consortium, NAVIGATE-ESUS trial investigators (Clinicatrials.gov identifier NCT02313909) and American Association of Neurological Surgeons. Demographic factors and 11 clinical scenarios were included. Two hundred twenty-eight participants from 38 countries completed the survey. Majority of participants were affiliated with academic centers, and >20% managed more than 15 OAC-associated ICH patients/year. Proportion of respondents suggesting OAC anticoagulant resumption varied from 30% (for cerebral amyloid angiopathy) to 98% (for traumatic ICH). Within this group, there was wide distribution in response for timing of resumption: 21.4% preferred to re-start OACs after 1-3 weeks of incident ICH, while 25.3% opted to start after 1-3 months. Neurosurgery respondents preferred earlier OAC resumption compared to stroke neurologists or thrombosis experts in 5 scenarios (p<0.05 by Kendall's tau). Wide variations in current practice exist among management of OAC-associated ICH, with decisions influenced by patient- and provider-related factors. As these variations likely reflect the lack of high quality evidence, randomized trials are direly needed in this population.

Cost-effectiveness of dabigatran versus vitamin K antagonists for the prevention of stroke in patients with atrial fibrillation: a French payer perspective.

PubMed

Chevalier, Julie; Delaitre, Olivier; Hammès, Florence; de Pouvourville, Gérard

2014-01-01

Atrial fibrillation is the main cause of stroke, but the risk can be reduced, usually with vitamin K antagonists (VKAs) such as warfarin. The RE-LY atrial fibrillation study demonstrated that the rates of stroke and systemic embolism with dabigatran (an oral direct thrombin inhibitor) were similar to or lower than those with warfarin. To estimate the cost-effectiveness, from a French payer perspective, of dabigatran (150 or 110mg bid for patients

Community-Based Intervention to Improve Cardiometabolic Targets in Patients With Stroke: A Randomized Controlled Trial.

PubMed

Olaiya, Muideen T; Cadilhac, Dominique A; Kim, Joosup; Nelson, Mark R; Srikanth, Velandai K; Gerraty, Richard P; Bladin, Christopher F; Fitzgerald, Sharyn M; Phan, Thanh; Frayne, Judith; Thrift, Amanda G

2017-09-01

Many guidelines for secondary prevention of stroke focus on controlling cardiometabolic risk factors. We investigated the effectiveness of a management program for attaining cardiometabolic targets in survivors of stroke/transient ischemic attack. Randomized controlled trial of survivors of stroke/transient ischemic attack aged ≥18 years. General practices were randomized to usual care (control) or an intervention comprising specialist review of care plans and nurse education in addition to usual care. The outcome is attainment of pre-defined cardiometabolic targets based on Australian guidelines. Multivariable regression was undertaken to determine efficacy and identify factors associated with attaining targets. Overall, 283 subjects were randomized to the intervention and 280 to controls. Although we found no between-group difference in overall cardiometabolic targets achieved at 12 months, the intervention group more often achieved control of low-density lipoprotein cholesterol (odds ratio, 1.97; 95% confidence interval, 1.18-3.29) than controls. At 24 months, no between-group differences were observed. Medication adherence was ≥80% at follow-up, but uptake of lifestyle/behavioral habits was poor. Older age, being male, being married/living with partner, and having greater functional ability or a history of diabetes mellitus were associated with attaining targets. The intervention in this largely negative trial only had a detectable effect on attaining target for lipids but not for other factors at 12 months or any factor at 24 months. This limited effect may be attributable to inadequate uptake of behavioral/lifestyle interventions, highlighting the need for new or better approaches to achieve meaningful behavioral change. URL: http://www.clinicaltrials.gov. Unique identifier: ACTRN12608000166370. © 2017 American Heart Association, Inc.

Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery.

PubMed

Rothwell, P M; Eliasziw, M; Gutnikov, S A; Warlow, C P; Barnett, H J M

2004-03-20

Carotid endarterectomy reduces the risk of stroke in patients with recently symptomatic stenosis. Benefit depends on the degree of stenosis, and we aimed to see whether it might also depend on other clinical and angiographic characteristics, and on the timing of surgery. We analysed pooled data from the European Carotid Surgery Trial and North American Symptomatic Carotid Endarterectomy Trial. The risk of ipsilateral ischaemic stroke for patients on medical treatment, the perioperative risk of stroke and death, and the overall benefit from surgery were determined in relation to seven predefined and seven post hoc subgroups. 5893 patients with 33000 patient-years of follow-up were analysed. Sex (p=0.003), age (p=0.03), and time from the last symptomatic event to randomisation (p=0.009) modified the effectiveness of surgery. Benefit from surgery was greatest in men, patients aged 75 years or older, and those randomised within 2 weeks after their last ischaemic event, and fell rapidly with increasing delay. For patients with 50% or higher stenosis, the number of patients needed to undergo surgery (ie, number needed to treat) to prevent one ipsilateral stroke in 5 years was nine for men versus 36 for women, five for age 75 years or older versus 18 for younger than 65 years, and five for those randomised within 2 weeks after their last ischaemic event, versus 125 for patients randomised after more than 12 weeks. These results were consistent across the individual trials. Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other clinical characteristics such as delay to surgery after the presenting event. Ideally, the procedure should be done within 2 weeks of the patient's last symptoms.

One swallow does not a summer make but many swallows do: accumulating clinical evidence for nearly-eliminated peri-procedural and 30-day complications with mesh-covered stents transforms the carotid revascularisation field

PubMed Central

Hopkins, L. Nelson; Siddiqui, Adnan H.

2017-01-01

Atherosclerotic carotid artery stenosis (CS) continues to be a common cause of acute ischaemic stroke. Optimised medical therapy (OMT), the first-line treatment modality in CS, may reduce or delay – but it does not abolish – CS-related strokes. As per current AHA/ASA and ESC/ESVS/ESO guidelines, carotid artery stenting (CAS) is a less-invasive alternative to carotid endarterectomy (CEA) for CS revascularisation in primary and secondary stroke prevention. Ten-year follow-up from the CREST trial in patients with symptomatic and asymptomatic CS confirmed equipoise of CAS and CEA in the primary endpoint. Nevertheless CAS – using a widely open-cell, first-generation stent and first-generation (distal/filter) neuroprotection – has been criticised for its relative excess of (mostly minor) strokes by 30 days, a significant proportion of which were post-procedural. Atherosclerotic plaque protrusion through conventional carotid stent struts, confirmed on intravascular imaging, has been implicated as a leading mechanism of the relative excess of strokes with CAS vs. CEA, including delayed strokes with CAS. Different designs of mesh-covered carotid stents have been developed to prevent plaque prolapse. Several multi-centre/multi-specialty clinical studies with CGurad MicroNet-Covered Embolic Prevention Stent System (EPS) and RoadSaver/Casper were recently published and included routine DW-MRI cerebral imaging peri-procedurally and at 30 days (CGuard EPS). Data from more than 550 patients in mesh-covered carotid stent clinical studies to-date show an overall 30-day complication rate of ~1% with near-elimination of post-procedural events. While more (and long-term) evidence is still anticipated, these results – taken together with optimised intra-procedural neuroprotection in CAS (increased use of proximal systems including trans-carotid dynamic flow reversal) and the positive 12-month mesh-covered stent data reports in 2017 – are transforming the carotid revascularisation field today. Establishing effective algorithms to identify the asymptomatic subjects at stroke risk despite OMT, and large-scale studies with mesh-covered stents including long-term clinical and duplex ultrasound outcomes, are the next major goals. PMID:28798779

Endovascular treatment with angioplasty or stenting versus endarterectomy in patients with carotid artery stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial.

PubMed

Ederle, Jörg; Bonati, Leo H; Dobson, Joanna; Featherstone, Roland L; Gaines, Peter A; Beard, Jonathan D; Venables, Graham S; Markus, Hugh S; Clifton, Andrew; Sandercock, Peter; Brown, Martin M

2009-10-01

Endovascular treatment (angioplasty with or without stenting) is an alternative to carotid endarterectomy for carotid artery stenosis but there are scarce long-term efficacy data showing that it prevents stroke. We therefore report the long-term results of the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). Between March, 1992, and July, 1997, patients who presented at a participating centre with a confirmed stenosis of the internal carotid artery that was deemed equally suitable for either carotid endarterectomy or endovascular treatment were randomly assigned to either treatment in equal proportions by telephone or fax from the randomisation service at the Oxford Clinical Trials Unit, UK. Patients were seen by an independent neurologist at 1 and 6 months after treatment and then every year after randomisation for as long as possible, up to a maximum of 11 years. Major outcome events were transient ischaemic attack, non-disabling, disabling, and fatal stroke, myocardial infarction, and death from any other cause. Outcomes were adjudicated on by investigators who were masked to treatment. Analysis was by intention to treat. This study is registered, number ISRCTN 01425573. 504 patients with stenosis of the carotid artery (90% symptomatic) were randomly assigned to endovascular treatment (n=251) or surgery (n=253). Within 30 days of treatment, there were more minor strokes that lasted less than 7 days in the endovascular group (8 vs 1) but the number of other strokes in any territory or death was the same (25 vs 25). There were more cranial nerve palsies (22 vs 0) in the endarterectomy group than in the endovascular group. Median length of follow up in both groups was 5 years (IQR 2-6). By comparing endovascular treatment with endarterectomy after the 30-day post-treatment period, the 8-year incidence and hazard ratio (HR) at the end of follow-up for ipsilateral non-perioperative stroke was 11.3% versus 8.6% (HR 1.22, 95% CI 0.59-2.54); for ipsilateral non-perioperative stroke or TIA was 19.3% versus 17.2% (1.29, 0.78-2.14); and for any non-perioperative stroke was 21.1% versus 15.4% (1.66, 0.99-2.80). More patients had stroke during follow-up in the endovascular group than in the surgical group, but the rate of ipsilateral non-perioperative stroke was low in both groups and none of the differences in the stroke outcome measures was significant. However, the study was underpowered and the confidence intervals were wide. More long-term data are needed from the on going stenting versus endarterectomy trials. British Heart Foundation; UK National Health Service Management Executive; UK Stroke Association.

Stem cell transplantation for treating stroke: status, trends and development.

PubMed

Huo, Wenxin; Liu, Xiaoyang; Tan, Cheng; Han, Yingying; Kang, Chunyang; Quan, Wei; Chen, Jiajun

2014-09-01

The developing approaches of thrombolytic therapy, endovascular treatment, neuroprotective therapy, and stem cell therapy have enabled breakthroughs in stroke treatment. In this study, we summarize and analyze trends and progress in stem cell transplantation for stroke treatment by retrieval of literature from Thomson Reuters Web of Science database, the NIH Clinical Trial Planning Grant Program, and Clinical Trials Registration Center in North America. In the last 10 years, there has been an increasing number of published articles on stem cell transplantation for stroke treatment. In particular, research from the USA and China has focused on stem cell transplantation. A total of 2,167 articles addressing stem cell transplantation for stroke treatment from 2004 to 2013 were retrieved from the Thomson Reuters Web of Science database. The majority of these articles were from the USA (854, 39.4%), with the journal Stroke publishing the most articles (145, 6.7%). Of the published articles, 143 were funded by the National Institutes of Health (accounting for 6.6% of total publications), and 91 by the National Natural Science Foundation of China. Between 2013 and 2014, the National Institutes of Health provided financial support ($130 million subsidy) for 329 research projects on stroke therapy using stem cell transplantation. In 2014, 215 new projects were approved, receiving grants of up to $70,440,000. Ninety clinical trials focusing on stem cell transplantation for stroke were registered in the Clinical Trial Registration Center in North America, with 40 trials registered in the USA (ranked first place). China had the maximum number of registered research or clinical trials (10 projects).

Prevention and treatment of hand oedema after stroke.

PubMed

Kuppens, Stefanie P M; Pijlman, Hanneke C P; Hitters, Minou W M G C; van Heugten, Caroline M

2014-01-01

As there is no evidence for a specific treatment for post-stroke-induced hand oedema, rehabilitation centre Blixembosch formalized a best practice protocol. We investigated whether the Blixembosch hand oedema protocol is usable in daily practice and leads to lower incidence (prevention) and shorter duration (treatment) compared with care as usual. In a non-randomised comparative trial, we investigated 206 post-stroke patients admitted to two Dutch rehabilitation centres. Hand volumes were measured at least bi-weekly using a volumeter. Treatment was started according the protocol (Blixembosch) or following care as usual (Leijpark). Usability was assessed with a survey among professionals. In the Blixembosch group, 16% developed oedema after admission, compared with 21% in the control group (p = 0.019). Average duration of oedema (both developed before and after admission) was 6.5 weeks in the Blixembosch group compared with 3.1 weeks in the control group (p = 0.000). Professionals were positive about the protocol. The study showed that the protocol is usable in daily practice and has a small beneficial effect on hand oedema incidence rates compared with care as usual. The negative effect on duration of hand oedema could also be caused by the difference in prognosis between the two groups.

Development of a Mobile Tool That Semiautomatically Screens Patients for Stroke Clinical Trials.

PubMed

Spokoyny, Ilana; Lansberg, Maarten; Thiessen, Rosita; Kemp, Stephanie M; Aksoy, Didem; Lee, YongJae; Mlynash, Michael; Hirsch, Karen G

2016-10-01

Despite several national coordinated research networks, enrollment in many cerebrovascular trials remains challenging. An electronic tool was needed that would improve the efficiency and efficacy of screening for multiple simultaneous acute clinical stroke trials by automating the evaluation of inclusion and exclusion criteria, improving screening procedures and streamlining the communication process between the stroke research coordinators and the stroke clinicians. A multidisciplinary group consisting of physicians, study coordinators, and biostatisticians designed and developed an electronic clinical trial screening tool on a HIPAA (Health Insurance Portability and Accountability Act)-compliant platform. A web-based tool was developed that uses branch logic to determine eligibility for simultaneously enrolling clinical trials and automatically notifies the study coordinator teams about eligible patients. After 12 weeks of use, 225 surveys were completed, and 51 patients were enrolled in acute stroke clinical trials. Compared with the 12 weeks before implementation of the tool, there was an increase in enrollment from 16.5% of patients screened to 23.4% of patients screened (P<0.05). Clinicians and coordinators reported increased satisfaction with the process and improved ease of screening. We created a semiautomated electronic screening tool that uses branch logic to screen patients for stroke clinical trials. The tool has improved efficiency and efficacy of screening, and it could be adapted for use at other sites and in other medical fields. © 2016 American Heart Association, Inc.

Mixed methods feasibility study for a trial of blood pressure telemonitoring for people who have had stroke/transient ischaemic attack (TIA).

PubMed

Hanley, Janet; Fairbrother, Peter; Krishan, Ashma; McCloughan, Lucy; Padfield, Paul; Paterson, Mary; Pinnock, Hilary; Sheikh, Aziz; Sudlow, Cathie; Todd, Allison; McKinstry, Brian

2015-03-25

Good blood pressure (BP) control reduces the risk of recurrence of stroke/transient ischaemic attack (TIA). Although there is strong evidence that BP telemonitoring helps achieve good control, none of the major trials have considered the effectiveness in stroke/TIA survivors. We therefore conducted a feasibility study for a trial of BP telemonitoring for stroke/TIA survivors with uncontrolled BP in primary care. Phase 1 was a pilot trial involving 55 patients stratified by stroke/TIA randomised 3:1 to BP telemonitoring for 6 months or usual care. Phase 2 was a qualitative evaluation and comprised semi-structured interviews with 16 trial participants who received telemonitoring and 3 focus groups with 23 members of stroke support groups and 7 carers. Overall, 125 patients (60 stroke patients, 65 TIA patients) were approached and 55 (44%) patients were randomised including 27 stroke patients and 28 TIA patients. Fifty-two participants (95%) attended the 6-month follow-up appointment, but one declined the second daytime ambulatory blood pressure monitoring (ABPM) measurement resulting in a 93% completion rate for ABPM - the proposed primary outcome measure for a full trial. Adherence to telemonitoring was good; of the 40 participants who were telemonitoring, 38 continued to provide readings throughout the 6 months. There was a mean reduction of 10.1 mmHg in systolic ABPM in the telemonitoring group compared with 3.8 mmHg in the control group, which suggested the potential for a substantial effect from telemonitoring. Our qualitative analysis found that many stroke patients were concerned about their BP and telemonitoring increased their engagement, was easy, convenient and reassuring. A full-scale trial is feasible, likely to recruit well and have good rates of compliance and follow-up. ISRCTN61528726 15/12/2011.

Secondary prevention of stroke in Saskatchewan, Canada: hypertension control.

PubMed

Bartsch, Janelle Ann; Teare, Gary F; Neufeld, Anne; Hudema, Nedeene; Muhajarine, Nazeem

2013-10-01

In the province of Saskatchewan, Canada, stroke is the third leading cause of death as well as the major cause of adult disability. Once a person suffers a stroke or transient ischemic attack (TIA), they are at high risk for having a secondary stroke. Hypertension (elevated blood pressure) is the single most important modifiable risk factor for both first and recurrent stroke, and is thus an important risk factor to be controlled. According to the Canadian Stroke Strategy (CSS) Best Practice Recommendations, blood pressure lowering treatment should be initiated before discharge from hospital for all stroke/TIA patients. The purpose of this study was to examine the quality of medically driven secondary stroke prevention care in Saskatchewan as applied to hypertension control. The objectives of the study were to: (1) develop methodology and calculate a secondary stroke process of care measure using available data in Saskatchewan, based on an appropriate hypertension therapy indicator recommendation from the CSS Performance Measurement Manual; (2) examine variation in secondary stroke prevention hypertensive care among the Saskatchewan Regional Health Authorities; and (3) investigate factors associated with receiving evidence-based hypertensive secondary stroke prevention. This multi-year cross-sectional study was an analysis of deidentified health data derived from linkage of administrative health data. A select indicator from the CSS Performance Measurement Manual that measures adherence to a CSS Best Practice Guidelines concerning use of antihypertensive medications for secondary stroke prevention was calculated. Logistic regression was used to quantify the association of patient demographic and socioeconomic characteristics and geographic location of care with receipt of guideline-recommended hypertensive secondary stroke prevention. The target population was all Saskatchewan residents who were hospitalized in Saskatchewan for a stroke or TIA between April 1, 2001 and March 31, 2008. The results of this study indicate that the management of hypertension for secondary stroke prevention is sub-optimal in Saskatchewan. Although there was some improvement over the time period, approximately 40% of patients were not taking antihypertensives at 90 days after discharge from acute care. The correlates, urban/non-urban, previous use of antihypertensive drugs and effect of age modified by sex, were found to be significantly associated with receiving hypertensive secondary stroke prevention, suggesting there are modifiable factors that contribute to variations in this form of secondary stroke care quality in Saskatchewan. The results of this study suggest that there is a need for province-wide improvement to secondary stroke prevention in Saskatchewan, Canada. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Design and rationale of dabigatran's stroke prevention in real life in Turkey (D-SPIRIT).

PubMed

Türk, Uğur Önsel; Alioğlu, Emin; Tunçer, Eşref; Özpelit, Mehmet Emre; Pekel, Nihat; Tengiz, İstemihan; Çetin, Nurullah; Dalgıç, Onur; Topaloğlu, Caner; Bilgin, Nazile; Altın, Cihan; Özdemirkıran, Tolga; Tülüce, Kamil; Türkoğlu, Ebru İpek; Özpelit, Ebru

2016-04-01

The D-SPIRIT registry is designed to investigate the safety and efficacy of dabigatran etexilate in patients with nonvalvular atrial fibrillation (NVAF) and to collect data on outcomes in clinical practice. The D-SPIRIT is a national, prospective, observational, post-marketing registry involving patients with NVAF who have been taking dabigatran etexilate therapy for stroke prevention for a minimum of 6 months prior to enrollment. The registry will collect and analyze data from routine care, enrolling up to 600 patients in 9 centers. Patients will be followed up for 2 years to evaluate effectiveness and safety. A sample size of 600 subjects is proposed based on the following assumptions; Two-sided significance level of 0.05 (1-sided significance level of 0.025), ischemic stroke incidence rate of 0.768%-1.111%, hemorrhagic stroke incidence rate of 0.109%-0.130%, transient ischemic attack incidence rate of 0.722%-0.623%, therapy discontinuation incidence rate of 40% at day 730, and duration of enrollment period of 12 months with non-uniformed enrollment rate. Ethics approval was given by Dokuz Eylül University Ethics Committee of Clinical Research (2014/54) and approved by the Turkish Ministry of Health. Potential results of D-SPIRIT registry will add data from clinical practice to those from the RE-LY trial to expand knowledge of dabigatran etexilate treatment in patients with NVAF.

[Economic evaluation of dabigatran for stroke prevention in patients with non-valvular atrial fibrillation].

PubMed

Silva Miguel, Luís; Rocha, Evangelista; Ferreira, Jorge

2013-01-01

To estimate the cost-effectiveness and cost-utility of dabigatran in the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in Portugal. A Markov model was used to simulate patients' clinical course, estimating the occurrence of ischemic and hemorrhagic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and intra- and extracranial hemorrhage. The clinical parameters are based on the results of the RE-LY trial, which compared dabigatran with warfarin, and on a meta-analysis that estimated the risk of each event in patients treated with aspirin or with no antithrombotic therapy. Dabigatran provides an increase of 0.331 life years and 0.354 quality-adjusted life years for each patient. From a societal perspective, these clinical gains entail an additional expenditure of 2978 euros. Thus, the incremental cost is 9006 euros per life year gained and 8409 euros per quality-adjusted life year. The results show that dabigatran reduces the number of events, especially the most severe such as ischemic and hemorrhagic stroke, as well as their long-term sequelae. The expense of dabigatran is partially offset by lower event-related costs and by the fact that INR monitoring is unnecessary. It can thus be concluded that the use of dabigatran in clinical practice in Portugal is cost-effective. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Paracetamol (Acetaminophen) in stroke 2 (PAIS 2): protocol for a randomized, placebo-controlled, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke and a body temperature of 36.5 °C or above.

PubMed

de Ridder, Inger R; de Jong, Frank Jan; den Hertog, Heleen M; Lingsma, Hester F; van Gemert, H Maarten A; Schreuder, A H C M L Tobien; Ruitenberg, Annemieke; Maasland, E Lisette; Saxena, Ritu; Oomes, Peter; van Tuijl, Jordie; Koudstaal, Peter J; Kappelle, L Jaap; Algra, Ale; van der Worp, H Bart; Dippel, Diederik W J

2015-04-01

In the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 37.0 °C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 1.43; 95% confidence interval: 1.02-1.97). This relation was also found in the patients with a body temperature of 36.5 °C or higher (odds ratio 1.31; 95% confidence interval 1.01-1.68). These findings need confirmation. The study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 36.5 °C or above on functional outcome. The Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 0.05 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 36.5 °C or above will be included within 12 h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register. The primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression. If high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be available for many patients with acute stroke worldwide. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Recurrent Ischemic Lesions After Acute Atherothrombotic Stroke: Clopidogrel Plus Aspirin Versus Aspirin Alone.

PubMed

Hong, Keun-Sik; Lee, Seung-Hoon; Kim, Eung Gyu; Cho, Ki-Hyun; Chang, Dae Il; Rha, Joung-Ho; Bae, Hee-Joon; Lee, Kyung Bok; Kim, Dong Eog; Park, Jong-Moo; Kim, Hahn-Young; Cha, Jae-Kwan; Yu, Kyung-Ho; Lee, Yong-Seok; Lee, Soo Joo; Choi, Jay Chol; Cho, Yong-Jin; Kwon, Sun U; Kim, Gyeong-Moon; Sohn, Sung-Il; Park, Kwang-Yeol; Kang, Dong-Wha; Sohn, Chul-Ho; Lee, Jun; Yoon, Byung-Woo

2016-09-01

In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence. In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding. Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group. Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268. © 2016 American Heart Association, Inc.

Efficacy and safety of percutaneous left atrial appendage closure to prevent thromboembolic events in atrial fibrillation patients with high stroke and bleeding risk.

PubMed

Seeger, Julia; Bothner, Carlo; Dahme, Tillman; Gonska, Birgid; Scharnbeck, Dominik; Markovic, Sinisa; Rottbauer, Wolfgang; Wöhrle, Jochen

2016-03-01

The randomized PROTECT AF trial demonstrated non-inferiority of left atrial appendage (LAA) closure to oral anticoagulation with warfarin. Current guidelines give a class IIb recommendation for LAA closure. We evaluated the efficacy and safety of LAA closure in a consecutive series of non-valvular atrial fibrillation patients with contraindications to long-term oral anticoagulation or at high bleeding risk. 101 consecutive non-valvular atrial fibrillation patients (age 74.7 ± 7.5 years) at high risk for stroke (CHA2DS2-VASc Score 4.4 ± 1.6) and high bleeding risk (HAS-BLED Score 4.2 ± 1.3) received LAA closure with either the Watchman closure device (n = 38) or the Amplatzer cardiac plug (n = 63). Dual antiplatelet therapy with aspirin and clopidogrel was recommended for 3-6 months after device implantation, followed by long-term antiplatelet therapy with aspirin. No anticoagulation was given after device implantation. Mean follow-up was 400 days. One patient (1 %) experienced a transient ischemic attack, and two patients (2 %) suffered from ischemic stroke. While on recommended antiplatelet therapy, bleeding occurred in 12/101 patients (12 %). Bleeding was significantly reduced with 3 compared with 6 months dual antiplatelet therapy (3.0 vs. 16.2 %, p < 0.05) while ischemic or thrombotic events were similar. Left atrial appendage closure in patients with non-valvular atrial fibrillation and high risk for stroke and bleeding events effectively prevented stroke and reduced cerebral ischemic events compared to expected stroke rate according to CHA2DS2-VASc Score. Dual antiplatelet therapy for 3 months reduced the rate of bleeding events compared to 6 months therapy with no increase of thrombotic events.

Direct stimulation of angiotensin II type 2 receptor initiated after stroke ameliorates ischemic brain damage.

PubMed

Min, Li-Juan; Mogi, Masaki; Tsukuda, Kana; Jing, Fei; Ohshima, Kousei; Nakaoka, Hirotomo; Kan-No, Harumi; Wang, Xiao-Li; Chisaka, Toshiyuki; Bai, Hui-Yu; Iwanami, Jun; Horiuchi, Masatsugu

2014-08-01

Stroke is a leading cause of death and disability; however, meta-analysis of randomized controlled trials of blood pressure-lowering drugs in acute stroke has shown no definite evidence of a beneficial effect on functional outcome. Accumulating evidence suggests that angiotensin II type 1 receptor blockade with angiotensin II type 2 (AT2) receptor stimulation could contribute to protection against ischemic brain damage. We examined the possibility that direct AT2 receptor stimulation by compound 21 (C21) initiated even after stroke can prevent ischemic brain damage. Stroke was induced by middle cerebral artery (MCA) occlusion, and the area of cerebral infarction was measured by magnetic resonant imaging. C21 (10 µg/kg/day) treatment was initiated immediately after MCA occlusion by intraperitoneal injection followed by treatment with C21 once daily. We observed that ischemic area was enlarged in a time dependent fashion and decreased on day 5 after MCA occlusion. Treatment with C21 initiated after MCA occlusion significantly reduced the ischemic area, with improvement of neurological deficit in a time-dependent manner without affecting blood pressure. The decrease of cerebral blood flow after MCA occlusion was also ameliorated by C21 treatment. Moreover, treatment with C21 significantly attenuated superoxide anion production and expression of proinflammatory cytokines, monocyte chemoattractant protein 1, and tumor necrosis factor α. Interestingly, C21 administration significantly decreased blood-brain barrier permeability and cerebral edema on the ischemic side. These results provide new evidence that direct AT2 receptor stimulation with C21 is a novel therapeutic approach to prevent ischemic brain damage after acute stroke. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Secondary stroke prevention services in Canada: a cross-sectional survey and geospatial analysis of resources, capacity and geographic access

PubMed Central

Jewett, Lauren; Harroud, Adil; Hill, Michael D.; Côté, Robert; Wein, Theodore; Smith, Eric E.; Gubitz, Gord; Demchuk, Andrew M.; Sahlas, Demetrios J.; Gladstone, David J.; Lindsay, M. Patrice

2018-01-01

Background: Rapid assessment and management of transient ischemic attacks and nondisabling strokes by specialized stroke prevention services reduces the risk of recurrent stroke and improves outcomes. In Canada, with its vast geography and with 16.8% of the population living in rural areas, access to these services is challenging, and considerable variation in access to care exists. The purpose of this multiphase study was to identify sites across Canada providing stroke prevention services, evaluate resource capacity and determine geographic access for Canadians. Methods: We developed a Stroke Prevention Services Resource Inventory that contained 22 questions on the organization and delivery of stroke prevention services and quality monitoring. The inventory ran from November 2015 to January 2016 and was administered online. We conducted a geospatial analysis to estimate access by drive times. Considerations were made for hours of operation and access within and across provincial borders. Results: A total of 123 stroke prevention sites were identified, of which 119 (96.7%) completed the inventory. Most (95) are designated stroke prevention or rapid assessment clinics. Of the 119 sites, 68 operate full time, and 39 operate less than 2.5 days per week. A total of 87.3% of the Canadian population has access to a stroke prevention service within a 1-hour drive; however, only 69.2% has access to a service that operates 5-7 days a week. Allowing provincial border crossing improves access (< 6-h drive) for those who are beyond a 6-hour drive within their home province (3.4%). Interpretation: Most Canadians have reasonable geographic access to stroke prevention services. Allowing patients to cross borders improves the existing access for many, particularly some remote communities along the Ontario-Quebec and British Columbia-Alberta borders. PMID:29472251

Singapore Tele-technology Aided Rehabilitation in Stroke (STARS) trial: protocol of a randomized clinical trial on tele-rehabilitation for stroke patients.

PubMed

Koh, Gerald Choon-Huat; Yen, Shih Cheng; Tay, Arthur; Cheong, Angela; Ng, Yee Sien; De Silva, Deidre Anne; Png, Carolina; Caves, Kevin; Koh, Karen; Kumar, Yogaprakash; Phan, Shi Wen; Tai, Bee Choo; Chen, Cynthia; Chew, Effie; Chao, Zhaojin; Chua, Chun En; Koh, Yen Sin; Hoenig, Helen

2015-09-05

Most acute stroke patients with disabilities do not receive recommended rehabilitation following discharge to the community. Functional and social barriers are common reasons for non-adherence to post-discharge rehabilitation. Home rehabilitation is an alternative to centre-based rehabilitation but is costlier. Tele-rehabilitation is a possible solution, allowing for remote supervision of rehabilitation and eliminating access barriers. The objective of the Singapore Tele-technology Aided Rehabilitation in Stroke (STARS) trial is to determine if a novel tele-rehabilitation intervention for the first three months after stroke admission improves functional recovery compared to usual care. This is a single blind (evaluator blinded), parallel, two-arm randomised controlled trial study design involving 100 recent stroke patients. The inclusion criteria are age ≥40 years, having caregiver support and recent stroke defined as stroke diagnosis within 4 weeks. Consenting participants will be randomized with varying block size of 4 or 6 assuming a 1:1 treatment allocation with the participating centre as the stratification factor. The baseline assessment will be done within 4 weeks of stroke onset, followed by follow-up assessments at 3 and 6 months. The tele-rehabilitation intervention lasts for 3 months and includes exercise 5-days-a-week using an iPad-based system that allows recording of daily exercise with video and sensor data and weekly video-conferencing with tele-therapists after data review. Those allocated to the control group will receive usual care. The primary outcome measure is improvement in life task's social activity participation at three months as measured by the disability component of the Jette Late Life Functional and Disability Instrument (LLFDI). Secondary outcome variables consist of gait speed (Timed 5-Meter Walk Test) and endurance (Two-Minute Walk test), performance of basic activities of daily living (Shah-modified Barthel Index), balance confidence (Activities-Specific Balance Confidence Scale), patient self-reported health-related quality-of-life [Euro-QOL (EQ-5D)], health service utilization (Singapore Stroke Study Health Service Utilization Form) and caregiver reported stress (Zarit Caregiver Burden Inventory). The goal of this trial is to provide evidence on the potential benefit and cost-effectiveness of this novel tele-rehabilitation programme which will guide health care decision-making and potentially improve performance of post-stroke community-based rehabilitation. This trial protocol was registered under ClinicalTrials.gov on 18 July 2013 as study title "The Singapore Tele-technology Aided Rehabilitation in Stroke (STARS) Study" (ID: The STARS Study, ClinicalTrials.gov Identifier: NCT01905917 ).

Hip Hop Stroke: Study Protocol for a Randomized Controlled Trial to Address Stroke Literacy

PubMed Central

Williams, Olajide; Leighton-Herrmann, Ellyn; DeSorbo, Alexandra; Hecht, Mindy; Hedmann, Monique; Huq, Saima; Gerin, William; Chinchilli, Vernon; Ogedegbe, Gbenga; Noble, James

2015-01-01

Objective Stroke is the fifth leading cause of death and the leading cause of serious long-term adult disability in the US. Acute stroke treatments with intravenous thrombolysis and endovascular therapy are proven to reduce disability, however a critical limitation on their effectiveness is the narrow time window for administration, which is 4.5 hours and 6 hours respectively from the onset of symptoms. Our overarching goal is to reduce pre-hospital delays to acute stroke treatments in economically disadvantaged minority communities where the greatest delays exist, using Hip Hop Stroke. Methods Hip Hop Stroke (HHS) is a school-based, child-mediated, culturally-tailored stroke communication multimedia intervention developed using validated models of behavior change and designed to improve stroke literacy (knowledge of stroke symptoms, the urgent need to call 911, and prevention measures) of 4th, 5th and 6th grade students and their parents residing in poor urban communities. Children in the intervention arm will receive the HHS intervention, while those in the attentional control arm will receive standardized nutrition education based on the USDA's MyPyramid program. Children will be trained and motivated to share stroke information with their parents or other adult caregiver. Both children and parents will complete a stroke knowledge assessment at baseline, immediately following the program, and at 3-months post-program. The primary outcome is the effect of the child mediation on parental stroke literacy. Conclusion Stroke literate children, a captive audience in school systems, may represent a viable channel for spreading stroke information into households of poor urban communities where mass media stroke campaigns have shown the lowest penetration. These children may also call 911 when witnessing a stroke in their homes or communities. The HHS program may highlight the potential role of children in the chain of stroke recovery as a strategy for reducing prehospital delays to acute stroke treatment. PMID:26779395

Hip Hop Stroke: Study Protocol for a Randomized Controlled Trial to Address Stroke Literacy.

PubMed

Williams, Olajide; Leighton-Herrmann, Ellyn; DeSorbo, Alexandra; Hecht, Mindy; Hedmann, Monique; Huq, Saima; Gerin, William; Chinchilli, Vernon; Ogedegbe, Gbenga; Noble, James

2015-10-01

Stroke is the fifth leading cause of death and the leading cause of serious long-term adult disability in the US. Acute stroke treatments with intravenous thrombolysis and endovascular therapy are proven to reduce disability, however a critical limitation on their effectiveness is the narrow time window for administration, which is 4.5 hours and 6 hours respectively from the onset of symptoms. Our overarching goal is to reduce pre-hospital delays to acute stroke treatments in economically disadvantaged minority communities where the greatest delays exist, using Hip Hop Stroke. Hip Hop Stroke (HHS) is a school-based, child-mediated, culturally-tailored stroke communication multimedia intervention developed using validated models of behavior change and designed to improve stroke literacy (knowledge of stroke symptoms, the urgent need to call 911, and prevention measures) of 4 th , 5 th and 6 th grade students and their parents residing in poor urban communities. Children in the intervention arm will receive the HHS intervention, while those in the attentional control arm will receive standardized nutrition education based on the USDA's MyPyramid program. Children will be trained and motivated to share stroke information with their parents or other adult caregiver. Both children and parents will complete a stroke knowledge assessment at baseline, immediately following the program, and at 3-months post-program. The primary outcome is the effect of the child mediation on parental stroke literacy. Stroke literate children, a captive audience in school systems, may represent a viable channel for spreading stroke information into households of poor urban communities where mass media stroke campaigns have shown the lowest penetration. These children may also call 911 when witnessing a stroke in their homes or communities. The HHS program may highlight the potential role of children in the chain of stroke recovery as a strategy for reducing prehospital delays to acute stroke treatment.

Haemodilution for acute ischaemic stroke

PubMed Central

Chang, Timothy S; Jensen, Matthew B

2014-01-01

Background Ischaemic stroke interrupts the flow of blood to part of the brain. Haemodilution is thought to improve the flow of blood to the affected areas of the brain and thus reduce infarct size. Objectives To assess the effects of haemodilution in acute ischaemic stroke. Search methods We searched the Cochrane Stroke Group Trials Register (February 2014), the Cochrane Central Register of Controlled Trials (Issue 1, 2014), MEDLINE (January 2008 to October 2013) and EMBASE (January 2008 to October 2013). We also searched trials registers, scanned reference lists and contacted authors. For the previous version of the review, the authors contacted manufacturers and investigators in the field. Selection criteria Randomised trials of haemodilution treatment in people with acute ischaemic stroke. We included only trials in which treatment was started within 72 hours of stroke onset. Data collection and analysis Two review authors assessed trial quality and one review author extracted the data. Main results We included 21 trials involving 4174 participants. Nine trials used a combination of venesection and plasma volume expander. Twelve trials used plasma volume expander alone. The plasma volume expander was plasma alone in one trial, dextran 40 in 12 trials, hydroxyethyl starch (HES) in five trials and albumin in three trials. Two trials tested haemodilution in combination with another therapy. Evaluation was blinded in 14 trials. Five trials probably included some participants with intracerebral haemorrhage. Haemodilution did not significantly reduce deaths within the first four weeks (risk ratio (RR) 1.10; 95% confidence interval (CI) 0.90 to 1.34). Similarly, haemodilution did not influence deaths within three to six months (RR 1.05; 95% CI 0.93 to 1.20), or death and dependency or institutionalisation (RR 0.96; 95% CI 0.85 to 1.07). The results were similar in confounded and unconfounded trials, and in trials of isovolaemic and hypervolaemic haemodilution. No statistically significant benefits were documented for any particular type of haemodiluting agents, but the statistical power to detect effects of HES was weak. Six trials reported venous thromboembolic events. There was a tendency towards reduction in deep venous thrombosis or pulmonary embolism or both at three to six months’ follow-up (RR 0.68; 95% CI 0.37 to 1.24). There was no statistically significant increased risk of serious cardiac events among haemodiluted participants. Authors’ conclusions The overall results of this review showed no clear evidence of benefit of haemodilution therapy for acute ischaemic stroke. These results are compatible with no persuasive beneficial evidence of haemodilution therapy for acute ischaemic stroke. This therapy has not been proven to improve survival or functional outcome. PMID:25159027

Electromechanical-assisted training for walking after stroke.

PubMed

Mehrholz, Jan; Thomas, Simone; Werner, Cordula; Kugler, Joachim; Pohl, Marcus; Elsner, Bernhard

2017-05-10

Electromechanical- and robotic-assisted gait-training devices are used in rehabilitation and might help to improve walking after stroke. This is an update of a Cochrane Review first published in 2007. To investigate the effects of automated electromechanical- and robotic-assisted gait-training devices for improving walking after stroke. We searched the Cochrane Stroke Group Trials Register (last searched 9 August 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 8), MEDLINE in Ovid (1950 to 15 August 2016), Embase (1980 to 15 August 2016), CINAHL (1982 to 15 August 2016), AMED (1985 to 15 August 2016), Web of Science (1899 to 16 August 2016), SPORTDiscus (1949 to 15 September 2012), the Physiotherapy Evidence Database (PEDro) (searched 16 August 2016), and the engineering databases COMPENDEX (1972 to 16 November 2012) and Inspec (1969 to 26 August 2016). We handsearched relevant conference proceedings, searched trials and research registers, checked reference lists, and contacted authors in an effort to identify further published, unpublished, and ongoing trials. We included all randomised controlled trials and randomised controlled cross-over trials in people over the age of 18 years diagnosed with stroke of any severity, at any stage, in any setting, evaluating electromechanical- and robotic-assisted gait training versus normal care. Two review authors independently selected trials for inclusion, assessed methodological quality and risk of bias, and extracted the data. The primary outcome was the proportion of participants walking independently at follow-up. We included 36 trials involving 1472 participants in this review update. Electromechanical-assisted gait training in combination with physiotherapy increased the odds of participants becoming independent in walking (odds ratio (random effects) 1.94, 95% confidence interval (CI) 1.39 to 2.71; P < 0.001; I² = 8%; moderate-quality evidence) but did not significantly increase walking velocity (mean difference (MD) 0.04 m/s, 95% CI 0.00 to 0.09; P = 0.08; I² = 65%; low-quality evidence) or walking capacity (MD 5.84 metres walked in 6 minutes, 95% CI -16.73 to 28.40; P = 0.61; I² = 53%; very low-quality evidence). The results must be interpreted with caution because 1) some trials investigated people who were independent in walking at the start of the study, 2) we found variations between the trials with respect to devices used and duration and frequency of treatment, and 3) some trials included devices with functional electrical stimulation. Our planned subgroup analysis suggested that people in the acute phase may benefit, but people in the chronic phase may not benefit from electromechanical-assisted gait training. Post hoc analysis showed that people who are non-ambulatory at intervention onset may benefit, but ambulatory people may not benefit from this type of training. Post hoc analysis showed no differences between the types of devices used in studies regarding ability to walk, but significant differences were found between devices in terms of walking velocity. People who receive electromechanical-assisted gait training in combination with physiotherapy after stroke are more likely to achieve independent walking than people who receive gait training without these devices. We concluded that seven patients need to be treated to prevent one dependency in walking. Specifically, people in the first three months after stroke and those who are not able to walk seem to benefit most from this type of intervention. The role of the type of device is still not clear. Further research should consist of large definitive pragmatic phase III trials undertaken to address specific questions about the most effective frequency and duration of electromechanical-assisted gait training as well as how long any benefit may last.

The Risk of Paradoxical Embolism (RoPE) Study: developing risk models for application to ongoing randomized trials of percutaneous patent foramen ovale closure for cryptogenic stroke.

PubMed

Kent, David M; Thaler, David E

2011-07-27

Despite the diffusion into practice of percutaneous closure of a patent foramen ovale (PFO) in patients with cryptogenic stroke (CS), the benefits have not been demonstrated, and remain unclear. For any individual presenting with a PFO in the setting of CS, it is not clear whether the PFO is pathogenically-related to the index event or an incidental finding. Further, the overall rate of stroke recurrence is low in patients with CS and PFO. How patient-specific factors affect the likelihood that a discovered PFO is related to an index stroke or affect the risk of recurrence is not well understood. These probabilities are likely to be important determinants of the benefits of PFO closure in CS. The goal of the Risk of Paradoxical Embolism (RoPE) Study is to develop and test a set of predictive models that can identify those patients most likely to benefit from preventive treatments for PFO-related stroke recurrence, such as PFO closure. To do this, we will construct a database of patients with CS, both with and without PFO, by combining existing cohort studies. We will use this pooled database to identify patient characteristics associated with the presence (versus the absence) of a PFO, and to use this "PFO propensity" to estimate the patient-specific probability that a PFO was pathogenically related to the index stroke (Model #1). We will also develop, among patients with both a CS and a PFO, a predictive model to estimate patient-specific stroke recurrence risk based on clinical, radiographic and echocardiographic characteristics. (Model #2). We will then combine Models #1 and #2 into a composite index that can rank patients with CS and PFO by their conditional probability that their PFO was pathogenically related to the index stroke and the risk of stroke recurrence. Finally, we will apply this composite index to completed clinical trials (currently on-going) testing endovascular PFO closure against medical therapy, to stratify patients from low-expected-benefit to high-expected-benefit.

Searching for the Smoker's Paradox in Acute Stroke Patients Treated With Intravenous Thrombolysis.

PubMed

Hussein, Haitham M; Niemann, Nicki; Parker, Emily D; Qureshi, Adnan I

2017-07-01

Inconsistent evidence supports better outcome in smokers after stroke. Our study examines this association in a large sample of ischemic stroke treated with intravenous thrombolysis. Virtual International Stroke Trials Archive (VISTA) database, composed of individual patient data of multiple clinical trials, was queried. The primary outcome was functional independence at 3 months noted by modified Rankin Scale (mRS; a 7-point scale ranging from 0 [no deficit] to 6 [death]) score≤ 2. The secondary outcomes were National Institutes of Health Stroke Scale (NIHSS; stroke severity measure, ranging from 0 [no deficit] to 42 [most severe]) score at 24 hours and the occurrence of symptomatic intractracranial hemorrhage. A total of 5383 patients were included: 1501 current smokers and 3882 nonsmokers. Smokers were younger (60 ± 13 vs. 71 ± 12 years, p < .0001) and had lower median NIHSS score at baseline (12 [8-17] vs. 13 [9-18], p < .0001). The rate of favorable functional outcome (mRS ≤ 2) at 3 months was significantly higher among current smokers (49.7% vs. 39.5%, p < .0001) and with crude ORs of 1.52, 95% CI 1.33-1.72. The association became non-significant after adjusting for age (OR 1.11, 95% CI 0.97-1.27). Subgroup analysis by age/gender strata showed that current smoking was associated with favorable outcome only in women ≥ 65 years. Current smoking was also associated with lower rates of symptomatic intracranial hemorrhage (adjusted OR 0.55, 95% CI 0.39-0.79). Smokers experience their first ever stroke 11 years younger than nonsmokers. This age difference explains the association between current smoking and favorable functional outcome. Smoking is associated with occurrence of first ever stroke at a younger age, therefore, focus should be on smoking prevention and treatment. The decision to treat ischemic stroke patients with intravenous thrombolysis should not be influenced by the patients' smoking status. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Parkinson's disease patients undershoot target size in handwriting and similar tasks

PubMed Central

Van Gemmert, A W A; Adler, C; Stelmach, G

2003-01-01

Objectives:Previous research suggested that people with Parkinson's disease are able to increase handwriting stroke size up to 1.5 cm without an increase of stroke duration; whereas age matched individuals in normal health are able to modulate stroke size without changes in stroke duration for sizes up to 2 cm. This study was designed to test this finding by examining whether sizes larger than 1.5 cm show different relationships with stroke duration for patients with Parkinson's disease as compared with age matched controls. Methods:The study included 13 subjects with Parkinson's disease and 13 age matched controls. Participants were required to write a cursive "llllllll" pattern, or a cursive "lililili" pattern without the dots, at a comfortable speed and also as fast as possible, in five different sizes (1.0, 1.5, 2.0, 3.0, and 5.0 cm). The participants wrote with a ballpoint pen on a digitiser tablet. The target pattern was displayed at its required size on a screen, but disappeared as soon as the pen touched the surface of the digitiser tablet. Online visual monitoring of the hand was prevented by a cover over the digitiser. After each trial, the recorded movement of the tip of the pen was displayed with two lines to indicate whether the size requirement had been met. The writing conditions were presented in random order and consisted of 12 trials for each participant. Results:The results demonstrated that stroke size and duration produced by the participants with Parkinson's disease were independently modulated up to 1.5 cm; sizes over 1.5 cm resulted in progressive undershooting by patients with Parkinson's disease (PD). It was also shown that these participants modulated acceleration measures inefficiently as compared with controls. Conclusions:The findings suggest that individuals with Parkinson's disease writing at speed produce inadequate stroke sizes when these should equal or exceed 1.5 cm. PMID:14617705

Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.

PubMed

Avezum, Alvaro; Lopes, Renato D; Schulte, Phillip J; Lanas, Fernando; Gersh, Bernard J; Hanna, Michael; Pais, Prem; Erol, Cetin; Diaz, Rafael; Bahit, M Cecilia; Bartunek, Jozef; De Caterina, Raffaele; Goto, Shinya; Ruzyllo, Witold; Zhu, Jun; Granger, Christopher B; Alexander, John H

2015-08-25

Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves. We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.97 and HR, 0.84; 95%, CI 0.67-1.04; interaction P=0.38), causing less major bleeding (HR, 0.79; 95% CI, 0.61-1.04 and HR, 0.65; 95% CI, 0.55-0.77; interaction P=0.23), and reducing mortality (HR, 1.01; 95% CI, 0.84-1.22 and HR, 0.84; 95% CI, 0.73-0.96; interaction P=0.10). More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2015 American Heart Association, Inc.

Exercise Training and Recreational Activities to Promote Executive Functions in Chronic Stroke: A Proof-of-Concept Study

PubMed Central

Liu-Ambrose, Teresa; Eng, Janice J

2015-01-01

Background Stroke survivors represent a target population in need of intervention strategies to promote cognitive function and prevent dementia. Both exercise and recreational activities are promising strategies. We assessed the effect of a six-month exercise and recreation program on executive functions in adults with chronic stroke. Methods A six-month ancillary study within a multi-centre randomized trial. Twenty-eight chronic stroke survivors (i.e., ≥ 12 months since an index stroke) were randomized to one of two experimental groups: intervention (INT; n=12) or delayed intervention (D-INT; n=16). Participants of the INT group received a six-month community-based structured program that included two sessions of exercise training and one session of recreation and leisure activities per week. Participants of the D-INT group received usual care. The primary outcome measure was the Stroop Test, a cognitive test of selective attention and conflict resolution. Secondary cognitive measures included set shifting and working memory. Mood, functional capacity, and general balance and mobility were additional secondary outcome measures. Results Compared with the D-INT group, the INT group significantly improved selective attention and conflict resolution (p=0.02), working memory (p=0.04), and functional capacity (p=0.02) at the end of the six-month intervention period. Improved selective attention and conflict resolution was significantly associated with functional capacity at six months (r=0.39; p=0.04). Conclusions This is the first randomized study to demonstrate that an exercise and recreation program can significantly benefit executive functions in community-dwelling chronic stroke survivors who are mildly cognitively impaired – a population at high-risk for dementia and functional decline. Thus, clinicians should consider prescribing exercise and recreational activities in the cognitive rehabilitation of chronic stroke survivors. Clinical Trial Registration http://clinicaltrials.gov. Unique identifier: NCT01085240. PMID:25440324

Effect of acupuncture on insomnia following stroke: study protocol for a randomized controlled trial.

PubMed

Cao, Yan; Yin, Xuan; Soto-Aguilar, Francisca; Liu, Yiping; Yin, Ping; Wu, Junyi; Zhu, Bochang; Li, Wentao; Lao, Lixing; Xu, Shifen

2016-11-16

The incidence, mortality, and prevalence of stroke are high in China. Stroke is commonly associated with insomnia; both insomnia and stroke have been effectively treated with acupuncture for a long time. The aim of this proposed trial is to assess the therapeutic effect of acupuncture on insomnia following stroke. This proposed study is a single-center, single-blinded (patient-assessor-blinded), parallel-group randomized controlled trial. We will randomly assign 60 participants with insomnia following stroke into two groups in a 1:1 ratio. The intervention group will undergo traditional acupuncture that achieves the De-qi sensation, and the control group will receive sham acupuncture without needle insertion. The same acupoints (DU20, DU24, EX-HN3, EX-HN22, HT7, and SP6) will be used in both groups. Treatments will be given to all participants three times a week for the subsequent 4 weeks. The primary outcome will be the Pittsburgh Sleep Quality Index. The secondary outcomes will be: the Insomnia Severity Index; sleep efficacy, sleep awakenings, and total sleep time recorded via actigraphy; the National Institutes of Health Stroke Scale; the Stroke-Specific Quality of Life score; the Hospital Anxiety and Depression Scale. The use of estazolam will be permitted and regulated under certain conditions. Outcomes will be assessed at baseline, 2 weeks after treatment commencement, 4 weeks after treatment commencement, and at the 8-week follow-up. This proposed study will contribute to expanding knowledge about acupuncture treatment for insomnia following stroke. This will be a high-quality randomized controlled trial with strict methodology and few design deficits. It will investigate the effectiveness of acupuncture as an alternative treatment for insomnia following stroke. Chinese Clinical Trial Registry identifier: ChiCTR-IIC-16008382 . Registered on 28 April 2016.

Details of a prospective protocol for a collaborative meta-analysis of individual participant data from all randomized trials of intravenous rt-PA vs. control: statistical analysis plan for the Stroke Thrombolysis Trialists' Collaborative meta-analysis.

PubMed

2013-06-01

Thrombolysis with intravenous alteplase is both effective and safe when administered to particular types of patient within 4·5 hours of having an ischemic stroke. However, the extent to which effects might vary in different types of patient is uncertain. We describe the protocol for an updated individual patient data meta-analysis of trials of intravenous alteplase, including results from the recently reported third International Stroke Trial, in which a wide range of patients enrolled up to six-hours after stroke onset were randomized to alteplase vs. control. This protocol will specify the primary outcome for efficacy, specified prior to knowledge of the results from the third International Stroke Trial, as the proportion of patients having a 'favorable' stroke outcome, defined by modified Rankin Score 0-1 at final follow-up at three- to six-months. The primary analysis will be to estimate the extent to which the known benefit of alteplase on modified Rankin Score 0-1 diminishes with treatment delay, and the extent to which it is independently modified by age and stroke severity. Key secondary outcomes include effect of alteplase on death within 90 days; analyses of modified Rankin Score using ordinal, rather than dichotomous, methods; and effects of alteplase on symptomatic intracranial hemorrhage, fatal intracranial hemorrhage, symptomatic ischemic brain edema and early edema, effacement and/or midline shift. This collaborative meta-analysis of individual participant data from all randomized trials of intravenous alteplase vs. control will demonstrate how the known benefits of alteplase on ischemic stroke outcome vary across different types of patient. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

The efficacy and safety of novel oral anticoagulants for the preventive treatment in atrial fibrillation patients: a systematic review and meta-analysis.

PubMed

Liu, Guang Jian; Wang, Yun Fu; Chen, Ping You; Chang, Wei; Tu, Ming Li; Chang, Li Ying; Cheng, Ping; Luo, Jie

2014-09-01

Novel oral anticoagulants, including direct factor Xa inhibitors and direct factor IIa inhibitors, have been used to prevent stroke in patients with atrial fibrillation (AF) for a decade. In this study, the efficacy and safety of the novel oral anticoagulants were assessed in AF patients. No language restrictions were applied. Study selection and data extraction were carried out by searching PubMed, EMBASE, OVID, the BIOSIS, the Web of Science, Clinical Trials Registers, Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. Each database was searched from its inception date to June 2013. Using odds ratio (OR) as an indicator, we systematically evaluated the primary efficacy endpoints and safety endpoints, as well as 10 secondary endpoints. Compared to the control drugs, the novel oral anticoagulants showed an OR decreased by 26% (OR: 0.74, 95% confidence interval (CI): 0.62-0.88) for stroke or systemic embolism, decreased by 24% (OR: 0.76, 95% CI: 0.64-0.90) for major bleeding, decreased by 10% (OR: 0.90, 95% CI: 0.84-0.95) for death from any cause, decreased by 27% for disabling or fatal stroke (OR: 0.73, 95% CI: 0.54-0.97), decreased by 31% (OR: 0.69, 95% CI: 0.60-0.8) for fatal bleeding, and decreased by 8% (OR: 0.92, 95% CI: 0.88-0.95) for serious adverse events. However, there was no significant difference in acute myocardial infarction, systemic embolism, major bleeding or clinically relevant non-major, all bleeding events, all adverse events and liver function disorder, between the novel oral anticoagulants and control drugs (p > 0.05). Compared to the control drugs, the novel oral anticoagulants showed higher efficiency and safety in patients with AF, as evidenced by their superior performance not only in reducing the risk of stroke or systemic embolism with a lower risk of major bleeding but also in decreasing the incidence of death from any cause, disabling or fatal stroke, serious adverse events and fatal bleeding.

Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF).

PubMed

Sherwood, Matthew W; Douketis, James D; Patel, Manesh R; Piccini, Jonathan P; Hellkamp, Anne S; Lokhnygina, Yuliya; Spyropoulos, Alex C; Hankey, Graeme J; Singer, Daniel E; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Becker, Richard C

2014-05-06

During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32). TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Pediatric Stroke

MedlinePlus

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2011-02-28

... Project Division of Heart Disease and Stroke Prevention Management Information System--Revision--National... Prevention (CDC). Background and Brief Description CDC's Division of Heart Disease and Stroke Prevention... two programs: The National Heart Disease and Stroke Prevention Program (NHDSPP), and the Well...

Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50 trial.

PubMed

Morrow, David A; Scirica, Benjamin M; Fox, Keith A A; Berman, Gail; Strony, John; Veltri, Enrico; Bonaca, Marc P; Fish, Polly; McCabe, Carolyn H; Braunwald, Eugene

2009-09-01

Thrombin potently activates platelets via interaction with the protease-activated receptor 1. SCH 530348 is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin via antagonism of the protease-activated receptor 1. Because SCH 530348 does not interfere with other pathways for hemostasis, it is possible that SCH 530348 reduces thrombosis with less increase in bleeding than do other potent antiplatelet agents. TRA 2 degrees P-TIMI 50 is a phase III, randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of SCH 530348 during long-term treatment of patients with established atherosclerotic disease receiving standard therapy (up to 27,000). Eligible patients with a history of myocardial infarction, ischemic stroke, or peripheral arterial disease are randomized 1:1 to SCH 530348 2.5 mg daily or matched placebo until the end of study. Randomization is stratified by the qualifying disease and planned use of a thienopyridine. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, or urgent coronary revascularization. The major secondary end point is the composite of cardiovascular death, myocardial infarction, or stroke. The evaluation of long-term safety includes bleeding defined by the GUSTO and TIMI criteria. Recruitment began in September 2007. The trial will continue until 2,279 primary end points and 1,400 secondary end points are recorded with expected completion in 36 to 44 months from first enrollment. TRA 2 degrees P-TIMI 50 is evaluating whether a new approach to platelet inhibition via interruption of thrombin-mediated platelet activation reduces major cardiovascular events with a favorable safety profile in patients with established atherosclerosis.

Effect of Apixaban on All-Cause Death in Patients with Atrial Fibrillation: a Meta-Analysis Based on Imputed Placebo Effect.

PubMed

Guimarães, Patrícia O; Lopes, Renato D; Wojdyla, Daniel M; Abdul-Rahim, Azmil H; Connolly, Stuart J; Flaker, Greg C; Wang, Junyuan; Hanna, Michael; Granger, Christopher B; Wallentin, Lars; Lees, Kennedy R; Alexander, John H; McMurray, John J V

2017-06-01

Vitamin K antagonists (VKAs) are the standard of care for stroke prevention in patients with atrial fibrillation (AF); therefore, there is not equipoise when comparing newer oral anticoagulants with placebo in this setting. To explore the effect of apixaban on mortality in patients with AF, we performed a meta-analysis of apixaban versus placebo using a putative placebo analysis based on randomized controlled clinical trials that compared warfarin, aspirin, and no antithrombotic control. We used data from two prospective randomized controlled trials for our comparison of apixaban versus warfarin (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) and apixaban versus aspirin (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment). Using meta-analysis approaches, we indirectly compared apixaban with an imputed placebo with respect to the risk of death in patients with AF. We used results from meta-analyses of randomized trials as our reference for the comparison between warfarin and placebo/no treatment, and aspirin and placebo/no treatment. In these meta-analyses, a lower rate of death was seen both with warfarin (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.57-0.97) and aspirin (OR 0.86, 95% CI 0.69-1.07) versus placebo/no treatment. Using data from ARISTOTLE and AVERROES, apixaban reduced the risk of death by 34% (95% CI 12-50%; p = 0.004) and 33% (95% CI 6-52%; p = 0.02), respectively, when compared with an imputed placebo. The pooled reduction in all-cause death with apixaban compared with an imputed placebo was 34% (95% CI 18-47%; p = 0.0002). In patients with AF, indirect comparisons suggest that apixaban reduces all-cause death by approximately one third compared with an imputed placebo.

Human Vaccines & Immunotherapeutics

PubMed Central

Riedmann, Eva M.

2012-01-01

Two therapeutic HPV vaccine candidates successful in phase 1 Flu shot may prevent heart attacks and stroke CDX-1401 combined with TLR agonist: Positive phase 1 results Three MRSA vaccines in early clincial trials Ovarian cancer vaccine candidate DPX-Survivac: Positive interim results from phase 1 Chinese biotech partnership brings first hepatitis E vaccine to the market Therapeutic vaccine for treatment of genital herpes enters phase 2 Visionary concept: Printable vaccines PMID:23817319

Issues in recruiting community-dwelling stroke survivors to clinical trials: the AMBULATE trial.

PubMed

Lloyd, Gemma; Dean, Catherine M; Ada, Louise

2010-07-01

Recruitment to clinical trials is often slow and difficult, with a growing body of research examining this issue. However there is very little work related to stroke. The aim of this study was to examine the success and efficiency of recruitment of community-dwelling stroke survivors over the first two years of a clinical trial aiming to improve community ambulation. Recruitment strategies fell into 2 broad categories: (i) advertisement (such as newspaper advertising and media releases), and (ii) referral (via hospital and community physiotherapists, a stroke liaison officer and other researchers). Records were kept of the number of people who were screened, were eligible and were recruited for each strategy. The recruitment target of 60 in the first two years was not met. 111 stroke survivors were screened and 57 were recruited (i.e., a recruitment rate of 51%). The most successful strategy was referral via hospital-based physiotherapists (47% of recruited participants) and the least successful were media release and local newspaper advertising. The referral strategies were all more efficient than any of the advertisement strategies. In general, recruitment was inefficient and costly in terms of human resources. Given that stroke research is underfunded, it is important to find efficient ways of recruiting stroke survivors to clinical trials. An Australian national database similar to other disease-specific data bases (such as the National Cancer Database) is under development. In the interim, recruiting for several clinical trials at once may increase efficiency.

Primary and Secondary Stroke Prevention Using Left Atrial Appendage Closure with Watchman Devices in Atrial Fibrillation Patients: A Single Center Experience from Mainland China.

PubMed

Chen, Yanhong; Zhang, Yonghua; Huang, Weiping; Huang, Keqiang; Xu, Bei; Su, X I

2017-06-01

Atrial fibrillation (AF) is associated with increased stroke risk resulting from cardiac embolism of the left atrial appendage (LAA). Stroke tends to recur in NVAF patients. Yet safety and feasibility of secondary stroke preventions with LAA closure (LAAC) have not been assessed in detail. This retrospective study was designed to compare the feasibility and safety of LAAC in primary and secondary stroke preventions, in a real-world setting of Chinese patients. From 2014 to 2015, non-valvular AF patients with CHA2DS2-VASc ≥1 were selected for percutaneous LAAC operations. Outcome observations of primary and secondary stroke preventions with Watchman devices were analyzed and compared. Overall, 122 patients were included. LAAC with Watchman devices were attempted in 115 patients, of whom 68 were for primary stroke prevention and 47 were for secondary prevention. Both the CHA2DS2-VASc score and the HASBLED score were significantly higher in the secondary prevention group (4.09 ± 1.06 vs. 1.93 ± 1.09 for CHA2DS2-VASc and 1.83 ± 1.03 vs. 1.26 ± 0.87 for HASBLED, P < 0.01). In both groups LAAC were achieved with high successful rate (98.53% in the primary prevention group and 100% in the secondary prevention group, P > 0.05) and low complication rates. The stroke rates were at a low level in both groups (1.47% in primary prevention group vs. 2.13% in secondary prevention group, P > 0.05). In our initial single-center experience, percutaneous LAA closure was a feasible and safe procedure for both primary and secondary stroke preventions in Chinese patients with nonvalvular AF. © 2017 Wiley Periodicals, Inc.

Early mobilization after stroke: an example of an individual patient data meta-analysis of a complex intervention.

PubMed

Craig, Louise E; Bernhardt, Julie; Langhorne, Peter; Wu, Olivia

2010-11-01

Very early mobilization (VEM) is a distinctive characteristic of care in some stroke units; however, evidence of the effectiveness of this approach is limited. To date, only 2 phase II trials have compared VEM with standard care: A Very Early Rehabilitation Trial (AVERT) in Australia and the recently completed Very Early Rehabilitation or Intensive Telemetry after Stroke trial in the United Kingdom. The Very Early Rehabilitation or Intensive Telemetry after Stroke protocol was designed to complement that of AVERT in a number of key areas. The aim of this analysis was to investigate the impact of VEM on independence by pooling data from these 2 comparable trials. Individual data from the 2 trials were pooled. Overall, patients were between 27 and 97 years old, had first or recurring stroke, and were treated within 36 hours after stroke onset. The primary outcome was independence, defined as modified Rankin scale score of 0 to 2 at 3 months. The secondary outcomes included complications of immobility and activities of daily living. Logistic regression was used to assess the effect of VEM on outcome, adjusting for known confounders including age, baseline stroke severity, and premorbid modified Rankin scale score. Findings-All patients in AVERT and Very Early Rehabilitation or Intensive Telemetry after Stroke were included, resulting in 54 patients in the VEM group and 49 patients in the standard care group. The baseline characteristics of VEM patients were largely comparable with standard care patients. Time to first mobilization from symptom onset was significantly shorter among VEM patients (median, 21 hours; interquartile range, 15.8-27.8 hours) compared with standard care patients (median, 31 hours; interquartile range, 23.0-41.2 hours). VEM patients had significantly greater odds of independence compared with standard care patients (adjusted odds ratio, 3.11; 95% confidence interval, 1.03-9.33). Planned collaborations between stroke researchers to conduct trials with common protocols and outcome measures can help advance rehabilitation science. VEM was associated with improved independence at 3 months compared with standard care. However, both trials are limited by small sample sizes. Larger trials (such as AVERT phase III) are still needed in this field.

Stroke Prevention & Treatment: Diet & Nutrition

MedlinePlus

... Diet & Nutrition Advertising Policy Stroke Prevention & Treatment: Diet & Nutrition A healthy diet can reduce your risk for ... Dysphagia How does a stroke affect eating and nutrition? Stroke can devastate a person's nutritional health because ...

Acute ischemic cerebrovascular events on antiplatelet therapy: what is the optimal prevention strategy?

PubMed

Milionis, Haralampos; Michel, Patrik

2013-01-01

Even though patients who develop ischemic stroke despite taking antiplatelet drugs represent a considerable proportion of stroke hospital admissions, there is a paucity of data from investigational studies regarding the most suitable therapeutic intervention. There have been no clinical trials to test whether increasing the dose or switching antiplatelet agents reduces the risk for subsequent events. Certain issues have to be considered in patients managed for a first or recurrent stroke while receiving antiplatelet agents. Therapeutic failure may be due to either poor adherence to treatment, associated co-morbid conditions and diminished antiplatelet effects (resistance to treatment). A diagnostic work up is warranted to identify the etiology and underlying mechanism of stroke, thereby guiding further management. Risk factors (including hypertension, dyslipidemia and diabetes) should be treated according to current guidelines. Aspirin or aspirin plus clopidogrel may be used in the acute and early phase of ischemic stroke, whereas in the long-term, antiplatelet treatment should be continued with aspirin, aspirin/extended release dipyridamole or clopidogrel monotherapy taking into account tolerance, safety, adherence and cost issues. Secondary measures to educate patients about stroke, the importance of adherence to medication, behavioral modification relating to tobacco use, physical activity, alcohol consumption and diet to control excess weight should also be implemented.

Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats

PubMed Central

Weise, Gesa; Lorenz, Marlene; Pösel, Claudia; Maria Riegelsberger, Ute; Störbeck, Veronika; Kamprad, Manja; Kranz, Alexander; Wagner, Daniel-Christoph; Boltze, Johannes

2014-01-01

Previous studies have highlighted the enormous potential of cell-based therapies for stroke not only to prevent ischemic brain damage, but also to amplify endogenous repair processes. Considering its widespread availability and low immunogenicity human umbilical cord blood (HUCB) is a particularly attractive stem cell source. Our goal was to investigate the neurorestorative potential of cryopreserved HUCB mononuclear cells (MNC) after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). Human umbilical cord blood MNC or vehicle solution was administered intravenously 24 hours after MCAO. Experimental groups were as follows: (1) quantitative polymerase chain reaction (PCR) of host-derived growth factors up to 48 hours after stroke; (2) immunohistochemical analysis of astroglial scarring; (3) magnetic resonance imaging (MRI) and weekly behavioral tests for 2 months after stroke. Long-term functional outcome and lesion development on MRI were not beneficially influenced by HUCB MNC therapy. Furthermore, HUCB MNC treatment did not change local growth factor levels and glial scarring extent. In summary, we could not demonstrate neurorestorative properties of HUCB MNC after stroke in SHR. Our results advise caution regarding a prompt translation of cord blood therapy into clinical stroke trials as long as deepened knowledge about its precise modes of action is missing. PMID:24169850

Factors Associated With Major Bleeding Events

PubMed Central

Goodman, Shaun G.; Wojdyla, Daniel M.; Piccini, Jonathan P.; White, Harvey D.; Paolini, John F.; Nessel, Christopher C.; Berkowitz, Scott D.; Mahaffey, Kenneth W.; Patel, Manesh R.; Sherwood, Matthew W.; Becker, Richard C.; Halperin, Jonathan L.; Hacke, Werner; Singer, Daniel E.; Hankey, Graeme J.; Breithardt, Gunter; Fox, Keith A. A.; Califf, Robert M.

2014-01-01

Objectives This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). Background The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. Methods The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. Results The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. Conclusions Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767) PMID:24315894

Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial.

PubMed

Piccini, Jonathan P; Stevens, Susanna R; Lokhnygina, Yuliya; Patel, Manesh R; Halperin, Jonathan L; Singer, Daniel E; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Breithardt, Günter

2013-05-14

This study sought to investigate the outcomes following cardioversion or catheter ablation in patients with atrial fibrillation (AF) treated with warfarin or rivaroxaban. There are limited data on outcomes following cardioversion or catheter ablation in AF patients treated with factor Xa inhibitors. We compared the incidence of electrical cardioversion (ECV), pharmacologic cardioversion (PCV), or AF ablation and subsequent outcomes in patients in a post hoc analysis of the ROCKET AF (Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation) trial. Over a median follow-up of 2.1 years, 143 patients underwent ECV, 142 underwent PCV, and 79 underwent catheter ablation. The overall incidence of ECV, PCV, or AF ablation was 1.45 per 100 patient-years (n = 321; 1.44 [n = 161] in the warfarin arm, 1.46 [n = 160] in the rivaroxaban arm). The crude rates of stroke and death increased in the first 30 days after cardioversion or ablation. After adjustment for baseline differences, the long-term incidence of stroke or systemic embolism (hazard ratio [HR]: 1.38; 95% confidence interval [CI]: 0.61 to 3.11), cardiovascular death (HR: 1.57; 95% CI: 0.69 to 3.55), and death from all causes (HR: 1.75; 95% CI: 0.90 to 3.42) were not different before and after cardioversion or AF ablation. Hospitalization increased after cardioversion or AF ablation (HR: 2.01; 95% CI: 1.51 to 2.68), but there was no evidence of a differential effect by randomized treatment (p value for interaction = 0.58). The incidence of stroke or systemic embolism (1.88% vs. 1.86%) and death (1.88% vs. 3.73%) were similar in the rivaroxaban-treated and warfarin-treated groups. Despite an increase in hospitalization, there were no differences in long-term stroke rates or survival following cardioversion or AF ablation. Outcomes were similar in patients treated with rivaroxaban or warfarin. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation [ROCKET AF]; NCT00403767). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Endarterectomy achieves lower stroke and death rates compared with stenting in patients with asymptomatic carotid stenosis.

PubMed

Kakkos, Stavros K; Kakisis, Ioannis; Tsolakis, Ioannis A; Geroulakos, George

2017-08-01

It is currently unclear if carotid artery stenting (CAS) is as safe as carotid endarterectomy (CEA) for patients with significant asymptomatic stenosis. The aim of our study was to perform a systematic review and meta-analysis of trials comparing CAS with CEA. On March 17, 2017, a search for randomized controlled trials was performed in MEDLINE and Scopus databases with no time limits. We performed meta-analyses with Peto odds ratios (ORs) and 95% confidence intervals (CIs). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation method. The primary safety and efficacy outcome measures were stroke or death rate at 30 days and ipsilateral stroke at 1 year (including ipsilateral stroke and death rate at 30 days), respectively. Perioperative stroke, ipsilateral stroke, myocardial infarction (MI), and cranial nerve injury (CNI) were all secondary outcome measures. The systematic review of the literature identified nine randomized controlled trials reporting on 3709 patients allocated into CEA (n = 1479) or CAS (n = 2230). Stroke or death rate at 30 days was significantly higher for CAS (64/2176 [2.94%]) compared with CEA (27/1431 [1.89%]; OR, 1.57; 95% CI, 1.01-2.44; P = .044), with low level of heterogeneity beyond chance (I 2  = 0%). Also, stroke rate at 30 days was significantly higher for CAS (63/2176 [2.90%]) than for CEA (26/1431 [1.82%]; OR, 1.63; 95% CI, 1.04-2.54; P = .032; I 2  = 0%). MI at 30 days was nonsignificantly lower for CAS (12/1815 [0.66%]) compared with CEA (16/1070 [1.50%]; OR, 0.53; 95% CI, 0.24-1.14; P = .105; I 2  = 0%); however, CNI at 30 days was significantly lower for CAS (2/1794 [0.11%]) than for CEA (33/1061 [3.21%]; OR, 0.13; 95% CI, 0.07-0.26; P < .00001; I 2  = 0%). Regarding the long-term outcome of stroke or death rate at 30 days plus ipsilateral stroke during follow-up, this was significantly higher for CAS (79/2173 [3.64%]) than for CEA (35/1430 [2.45%]; OR, 1.51; 95% CI, 1.02-2.24; P = .04; I 2  = 0%). Quality of evidence for all stroke outcomes was graded moderate. Among patients with asymptomatic stenosis undergoing carotid intervention, there is moderate-quality evidence to suggest that CEA had significantly lower 30-day stroke and also stroke or death rates compared with CAS at the cost of higher CNI and nonsignificantly higher MI rates. The long-term efficacy of CEA in ipsilateral stroke prevention, taking into account perioperative stroke and death, was preserved during follow-up. There is an urgent need for high-quality research before a firm recommendation is made that CAS is inferior or not to CEA. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Guidelines for the Primary Prevention of Stroke

PubMed Central

Meschia, James F.; Bushnell, Cheryl; Boden-Albala, Bernadette; Braun, Lynne T.; Bravata, Dawn M.; Chaturvedi, Seemant; Creager, Mark A.; Eckel, Robert H.; Elkind, Mitchell S.V.; Fornage, Myriam; Goldstein, Larry B.; Greenberg, Steven M.; Horvath, Susanna E.; Iadecola, Costantino; Jauch, Edward C.; Moore, Wesley S.; Wilson, John A.

2016-01-01

The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of stroke among individuals who have not previously experienced a stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches to atherosclerotic disease of the cervicocephalic circulation, and antithrombotic treatments for preventing thrombotic and thromboembolic stroke. Further recommendations are provided for genetic and pharmacogenetic testing and for the prevention of stroke in a variety of other specific circumstances, including sickle cell disease and patent foramen ovale. PMID:25355838

USE OF STROKE SECONDARY PREVENTION SERVICES

PubMed Central

Ross, Joseph S.; Halm, Ethan A.; Bravata, Dawn M.

2009-01-01

Objective To examine whether there are disparities in use of stroke secondary prevention services because disparities in stroke outcomes have been found among older adults, women, racial minorities, and within Stroke Belt states. Methods Using the nationally-representative 2005 Behavior Risk Factor Surveillance System, we examined self-reported use of 11 stroke secondary prevention services queried in the survey. We used multivariable logistic regression to examine the association between service use and age, sex, race, and Stroke Belt state residence, controlling for other socio-demographic and health care access characteristics. Results Among 11,862 adults with a history of stroke, 16% were 80 or older, 54% were women, 13% were non-Hispanic black, and 23% lived within a Stroke Belt state. Overall service use varied: 31% reported post-stroke outpatient rehabilitation, 57% regular exercise, 66% smoking cessation counseling, and 91% current use of anti-hypertensive medications. Age 80 or older was not associated with lower use of any of the 11 services. Women were less likely to report post-stroke outpatient rehabilitation and regular exercise when compared with men (P values ≤ 0.005); there were no sex-based differences in use of the 9 other services. Blacks were less likely to report pneumococcal vaccination when compared with whites, but were more likely to report post-stroke outpatient rehabilitation (P values ≤ 0.005); there were no race-based differences in use of the 9 other services. Stroke Belt state residence was not associated with lower use of any of the 11 services. Conclusions Use of many stroke secondary prevention services was suboptimal. We did not find consistent age, sex, racial, or Stroke Belt state residence disparities in care. CONDENSED ABSTRACT We examined the association between stroke secondary prevention service use and age, sex, race, and Stroke Belt state residence using nationally-representative data. Although use of many stroke secondary prevention services was suboptimal, we did not find consistent age, sex, racial, or Stroke Belt state residence disparities in care. PMID:19265044

How I treat and manage strokes in sickle cell disease

PubMed Central

Kassim, Adetola A.; Galadanci, Najibah A.; Pruthi, Sumit

2015-01-01

Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ∼11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by a multidisciplinary team (a hematologist, neurologist, neuroradiologist, and transfusion medicine specialist); prompt neuro-imaging and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion) is recommended if the hemoglobin is >4 gm/dL and <10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in SCD. PMID:25824688

Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials.

PubMed

Bath, Philip M; Woodhouse, Lisa; Krishnan, Kailash; Anderson, Craig; Berge, Eivind; Ford, Gary A; Robinson, Thompson G; Saver, Jeffrey L; Sprigg, Nikola; Wardlaw, Joanna M; In Acute Stroke Collaboration Basc, Blood Pressure

2016-01-01

Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4-6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34-0.78) and reduced death (OR 0.32, 95% CI 0.14-0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

CSDC: a nationwide screening platform for stroke control and prevention in China.

PubMed

Jinghui Yu; Huajian Mao; Mei Li; Dan Ye; Dongsheng Zhao

2016-08-01

As a leading cause of severe disability and death, stroke places an enormous burden on Chinese society. A nationwide stroke screening platform called CSDC (China Stoke Data Center) has been built to support the national stroke prevention program and stroke clinical research since 2011. This platform is composed of a data integration system and a big data analysis system. The data integration system is used to collect information on risk factors, diagnosis history, treatment, and sociodemographic characteristics and stroke patients' EMR. The big data analysis system support decision making of stroke control and prevention, clinical evaluation and research. In this paper, the design and implementation of CSDC are illustrated, and some application results are presented. This platform is expected to provide rich data and powerful tool support for stroke control and prevention in China.

Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation.

PubMed

Bruins Slot, Karsten Mh; Berge, Eivind

2018-03-06

Factor Xa inhibitors and vitamin K antagonists (VKAs) are now recommended in treatment guidelines for preventing stroke and systemic embolic events in people with atrial fibrillation (AF). This is an update of a Cochrane review previously published in 2013. To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for preventing cerebral or systemic embolic events in people with AF. We searched the trials registers of the Cochrane Stroke Group and the Cochrane Heart Group (September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (August 2017), MEDLINE (1950 to April 2017), and Embase (1980 to April 2017). We also contacted pharmaceutical companies, authors and sponsors of relevant published trials. We used outcome data from marketing authorisation applications of apixaban, edoxaban and rivaroxaban that were submitted to regulatory authorities in Europe and the USA. We included randomised controlled trials (RCTs) that directly compared the effects of long-term treatment (lasting more than four weeks) with factor Xa inhibitors versus VKAs for preventing cerebral and systemic embolism in people with AF. The primary efficacy outcome was the composite endpoint of all strokes and systemic embolic events. Two review authors independently extracted data, and assessed the quality of the trials and the risk of bias. We calculated a weighted estimate of the typical treatment effect across trials using the odds ratio (OR) with 95% confidence interval (CI) by means of a fixed-effect model. In case of moderate or high heterogeneity of treatment effects, we used a random-effects model to compare the overall treatment effects. We also performed a pre-specified sensitivity analysis excluding any open-label studies. We included data from 67,688 participants randomised into 13 RCTs. The included trials directly compared dose-adjusted warfarin with either apixaban, betrixaban, darexaban, edoxaban, idraparinux, idrabiotaparinux, or rivaroxaban. The majority of the included data (approximately 90%) was from apixaban, edoxaban, and rivaroxaban.The composite primary efficacy endpoint of all strokes (both ischaemic and haemorrhagic) and non-central nervous systemic embolic events was reported in all of the included studies. Treatment with a factor Xa inhibitor significantly decreased the number of strokes and systemic embolic events compared with dose-adjusted warfarin in participants with AF (OR 0.89, 95% CI 0.82 to 0.97; 13 studies; 67,477 participants; high-quality evidence).Treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.78, 95% CI 0.73 to 0.84; 13 studies; 67,396 participants; moderate-quality evidence). There was, however, statistically significant and high heterogeneity (I 2 = 83%). When we repeated this analysis using a random-effects model, it did not show a statistically significant decrease in the number of major bleedings (OR 0.88, 95% CI 0.66 to 1.17). A pre-specified sensitivity analysis excluding all open-label studies showed that treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.75, 95% CI 0.69 to 0.81), but high heterogeneity was also observed in this analysis (I 2 = 72%). The same sensitivity analysis using a random-effects model also showed a statistically significant decrease in the number of major bleedings in participants treated with factor Xa inhibitors (OR 0.76, 95% CI 0.60 to 0.96).Treatment with a factor Xa inhibitor significantly reduced the risk of intracranial haemorrhages (ICHs) compared with warfarin (OR 0.50, 95% CI 0.42 to 0.59; 12 studies; 66,259 participants; high-quality evidence). We observed moderate, but statistically significant heterogeneity (I 2 = 55%). The pre-specified sensitivity analysis excluding open-label studies showed that treatment with a factor Xa inhibitor significantly reduced the number of ICHs compared with warfarin (OR 0.47, 95% CI 0.40 to 0.56), with low, non-statistically significant heterogeneity (I 2 = 27%).Treatment with a factor Xa inhibitor also significantly reduced the number of all-cause deaths compared with warfarin (OR 0.89, 95% 0.83 to 0.95; 10 studies; 65,624 participants; moderate-quality evidence). Treatment with factor Xa inhibitors significantly reduced the number of strokes and systemic embolic events compared with warfarin in people with AF. The absolute effect of factor Xa inhibitors compared with warfarin treatment was, however, rather small. Factor Xa inhibitors also reduced the number of ICHs, all-cause deaths and major bleedings compared with warfarin, although the evidence for a reduction in the latter is less robust.

Quality of full and final publications reporting acute stroke trials: a systematic review.

PubMed

Bath, F J; Owen, V E; Bath, P M

1998-10-01

Several studies have shown that the quality of reporting of trials throughout medicine is variable and often poor. We report on the quality of the final reports of randomized controlled trials (RCTs) of drug therapies assessed in acute stroke. English-language reports published up to the end of 1996 relating to completed RCTs in acute stroke were identified from electronic searches of the Cochrane Stroke Review Group database of stroke trials and the Cochrane Controlled Trials Register (CD-ROM issue 1, 1997, of the Cochrane Library). Report quality was assessed with the 33 criteria of the CONSORT statement and 53 additional factors relevant to acute stroke or trials in general. Trial quality was also assessed with a 7-point scale. Up to 1996, 114 RCTs were published which involved 20 536 patients (median, 80; range, 16 to 1267 per trial); 39 (35.5%) of these were published in Stroke. The median total report quality was 40/86 (range, 15 to 61) for all criteria and 19/33 (range, 9 to 29) for the CONSORT criteria alone. Although adequate information was given in the introduction and discussion sections of most reports, insufficient details were given on methods, assignment of patients to treatment groups, statistical analyses, the prevalence of risk factors, and assessment of outcomes. Report quality has improved between 1956 and 1996 (Spearman correlation coefficient [rs], 0.575; 95% confidence interval [CI], 0. 439 to 0.685) and was superior in large trials (rs=0.434; 95% CI, 0. 274 to 0.571). Although report quality was related to trial quality (rs=0.675; 95% CI, 0.563 to 0.763), it was not related to journal impact factor (rs=0.170; 95% CI, -0.015 to 0.344). Trials with a positive outcome tended to be less well reported than those with a neutral or negative outcome (rs=-0.192; 95% CI, -0.351 to -0.011). The overall quality of study reports for parallel group RCTs in acute stroke is poor but appears to be improving with time and in parallel with an increase in trial size. Reports often lack detailed information on the methods of randomization, concealment of allocation, and statistical analysis, all factors which can, if undertaken poorly, affect trial results and validity. It is vital that future trials are adequately reported; we believe that authors should follow the CONSORT guidelines and that referees and editors should ensure this happens.

Promoting Recruitment using Information Management Efficiently (PRIME): a stepped-wedge, cluster randomised trial of a complex recruitment intervention embedded within the REstart or Stop Antithrombotics Randomised Trial.

PubMed

Maxwell, Amy E; Parker, Richard A; Drever, Jonathan; Rudd, Anthony; Dennis, Martin S; Weir, Christopher J; Al-Shahi Salman, Rustam

2017-12-28

Few interventions are proven to increase recruitment in clinical trials. Recruitment to RESTART, a randomised controlled trial of secondary prevention after stroke due to intracerebral haemorrhage, has been slower than expected. Therefore, we sought to investigate an intervention to boost recruitment to RESTART. We conducted a stepped-wedge, cluster randomised trial of a complex intervention to increase recruitment, embedded within the RESTART trial. The primary objective was to investigate if the PRIME complex intervention (a recruitment co-ordinator who conducts a recruitment review, provides access to bespoke stroke audit data exports, and conducts a follow-up review after 6 months) increases the recruitment rate to RESTART. We included 72 hospital sites located in England, Wales, or Scotland that were active in RESTART in June 2015. All sites began in the control state and were allocated using block randomisation stratified by hospital location (Scotland versus England/Wales) to start the complex intervention in one of 12 different months. The primary outcome was the number of patients randomised into RESTART per month per site. We quantified the effect of the complex intervention on the primary outcome using a negative binomial, mixed model adjusting for site, December/January months, site location, and background time trends in recruitment rate. We recruited and randomised 72 sites and recorded their monthly recruitment to RESTART over 24 months (March 2015 to February 2017 inclusive), providing 1728 site-months of observations for the primary analysis. The adjusted rate ratio for the number of patients randomised per month after allocation to the PRIME complex intervention versus control time before allocation to the PRIME complex intervention was 1.06 (95% confidence interval 0.55 to 2.03, p = 0.87). Although two thirds of respondents to the 6-month follow-up questionnaire agreed that the audit reports were useful, only six patients were reported to have been randomised using the audit reports. Respondents frequently reported resource and time pressures as being key barriers to running the audit reports. The PRIME complex intervention did not significantly improve the recruitment rate to RESTART. Further research is needed to establish if PRIME might be beneficial at an earlier stage in a prevention trial or for prevention dilemmas that arise more often in clinical practice.

CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot Trial: rationale and design.

PubMed

Potter, J; Robinson, T; Ford, G; James, M; Jenkins, D; Mistri, A; Bulpitt, C; Drummond, A; Jagger, C; Knight, J; Markus, H; Beevers, G; Dewey, M; Lees, K; Moore, A; Paul, S

2005-03-01

High and low blood pressure (BP) levels are common following acute stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly 20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours of ictus, both conditions being associated with an adverse prognosis. At present, the optimum management of blood pressure in the immediate post-stroke period is unclear. The primary aim of the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether hypertension and relative hypotension, manipulated therapeutically in the first 24 h following acute stroke, affects short-term outcome measures. The CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo-controlled, titrated dose trial. Acute stroke and medical units in teaching and district general hospitals, in the UK. The CHHIPS Pilot Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed by brain imaging, who have no compelling indication or contraindication for BP manipulation. The primary outcome measure will be the effects of acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post-stroke. Secondary outcome measures will include the influence of therapy on early neurological deterioration, the effectiveness of treatment in manipulating BP levels, the influence of time to treatment and stroke type on response and a cost-effectiveness analysis.

Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery.

PubMed

Duncan, Dallas; Sankar, Ashwin; Beattie, W Scott; Wijeysundera, Duminda N

2018-03-06

The surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may help prevent postoperative cardiac complications. To determine the efficacy and safety of α-2 adrenergic agonists for reducing mortality and cardiac complications in adults undergoing cardiac surgery and non-cardiac surgery. We searched CENTRAL (2017, Issue 4), MEDLINE (1950 to April Week 4, 2017), Embase (1980 to May 2017), the Science Citation Index, clinical trial registries, and reference lists of included articles. We included randomized controlled trials that compared α-2 adrenergic agonists (i.e. clonidine, dexmedetomidine or mivazerol) against placebo or non-α-2 adrenergic agonists. Included trials had to evaluate the efficacy and safety of α-2 adrenergic agonists for preventing perioperative mortality or cardiac complications (or both), or measure one or more relevant outcomes (i.e. death, myocardial infarction, heart failure, acute stroke, supraventricular tachyarrhythmia and myocardial ischaemia). Two authors independently assessed trial quality, extracted data and independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials. We evaluated included studies using the Cochrane 'Risk of bias' tool, and the quality of the evidence underlying pooled treatment effects using GRADE methodology. Given the clinical heterogeneity between cardiac and non-cardiac surgery, we analysed these subgroups separately. We expressed treatment effects as pooled risk ratios (RR) with 95% confidence intervals (CI). We included 47 trials with 17,039 participants. Of these studies, 24 trials only included participants undergoing cardiac surgery, 23 only included participants undergoing non-cardiac surgery and eight only included participants undergoing vascular surgery. The α-2 adrenergic agonist studied was clonidine in 21 trials, dexmedetomidine in 24 trials and mivazerol in two trials.In non-cardiac surgery, there was high quality evidence that α-2 adrenergic agonists led to a similar risk of all-cause mortality compared with control groups (1.3% with α-2 adrenergic agonists versus 1.7% with control; RR 0.80, 95% CI 0.61 to 1.04; participants = 14,081; studies = 16). Additionally, the risk of cardiac mortality was similar between treatment groups (0.8% with α-2 adrenergic agonists versus 1.0% with control; RR 0.86, 95% CI 0.60 to 1.23; participants = 12,525; studies = 5, high quality evidence). The risk of myocardial infarction was probably similar between treatment groups (RR 0.94, 95% CI 0.69 to 1.27; participants = 13,907; studies = 12, moderate quality evidence). There was no associated effect on the risk of stroke (RR 0.93, 95% CI 0.55 to 1.56; participants = 11,542; studies = 7; high quality evidence). Conversely, α-2 adrenergic agonists probably increase the risks of clinically significant bradycardia (RR 1.59, 95% CI 1.18 to 2.13; participants = 14,035; studies = 16) and hypotension (RR 1.24, 95% CI 1.03 to 1.48; participants = 13,738; studies = 15), based on moderate quality evidence.There was insufficient evidence to determine the effect of α-2 adrenergic agonists on all-cause mortality in cardiac surgery (RR 0.52, 95% CI 0.26 to 1.04; participants = 1947; studies = 16) and myocardial infarction (RR 1.01, 95% CI 0.43 to 2.40; participants = 782; studies = 8), based on moderate quality evidence. There was one cardiac death in the clonidine arm of a study of 22 participants. Based on very limited data, α-2 adrenergic agonists may have reduced the risk of stroke (RR 0.37, 95% CI 0.15 to 0.93; participants = 1175; studies = 7; outcome events = 18; low quality evidence). Conversely, α-2 adrenergic agonists increased the risk of bradycardia from 6.4% to 12.0% (RR 1.88, 95% CI 1.35 to 2.62; participants = 1477; studies = 10; moderate quality evidence), but their effect on hypotension was uncertain (RR 1.19, 95% CI 0.87 to 1.64; participants = 1413; studies = 9; low quality evidence).These results were qualitatively unchanged in subgroup analyses and sensitivity analyses. Our review concludes that prophylactic α-2 adrenergic agonists generally do not prevent perioperative death or major cardiac complications. For non-cardiac surgery, there is moderate-to-high quality evidence that these agents do not prevent death, myocardial infarction or stroke. Conversely, there is moderate quality evidence that these agents have important adverse effects, namely increased risks of hypotension and bradycardia. For cardiac surgery, there is moderate quality evidence that α-2 adrenergic agonists have no effect on the risk of mortality or myocardial infarction, and that they increase the risk of bradycardia. The quality of evidence was inadequate to draw conclusions regarding the effects of alpha-2 agonists on stroke or hypotension during cardiac surgery.

[Dabigatran versus warfarin for the prevention of stroke in Chinese patients with nonvalvular atrial fibrillation: Chinese subpopulation analysis of RE-LY].

PubMed

Gao, X; Yang, Y M; Zhu, J; Dai, Y; Tan, H Q

2016-11-24

Objective: This analysis was performed to evaluate the efficacy in stroke prevention and safety of dabigatran in Chinese nonvalvular atrial fibrillation(NVAF) patients enrolled in RE-LY trial. Methods: RE-LY was an prospective, open-label, randomized, multicenter study. From March 2006 to March 2009, 541 atrial fibrillation patients at risk of stroke were recruited from 13 medical centers in China. Patients randomly received, in a blinded fashion, fixed doses of dabigatran-110 mg or 150 mg twice daily or, in an unblinded fashion, adjusted-dose warfarin. The primary efficacy endpoint was stroke or systemic embolism. The primary safety endpoint was major bleeding. Results: The incidence of stroke in the Chinese subpopulation was 1.94% per year(7 cases) in the group that received 110 mg of dabigatran (dabigatran 110) and 1.10% per year(4 cases) in the group that received 150 mg of dabigatran (dabigatran 150), as compared with 2.87% per year (10 cases) in warfarin group . Incidence of ischemic stroke was 1.11% per year(4 patients) in dabigatran 110 group, 0.82% per year(3 cases) in dabigatran 150 group and 2.01% per year(7 patients) in warfarin group. Incidence of hemorrhagic stroke was 0.28% per year(1 case) in dabigatran 110 group, 0.27% per year(1 case) in dabigatran 150 group and 0.57% per year(2 cases) in warfarin group. All-cause mortality was similar among the three treatment groups: 3.33% per year(12 cases) in dabigatran 110, 2.19% per year(8 cases) in dabigatran 150 and 2.58% per year(9 cases) in warfarin group. Incidence of major bleeding event was 0.56% per year(2 cases) in both dabigatran groups, as compared with 1.43% per year(5 cases) in warfarin group. Gastrointestinal disorders such as dyspepsia occurred in 12.8% patients of both dabigatran groups, and in 5.6% patients of warfarin group. Conclusions: Despite the descriptive statistical analysis in nature of present study due to the limited number of subjects, our subgroup analysis implies that like warfarin, dabigatran is efficacious and safe for thromboembolism prevention in Chinese patients with atrial fibrillation at risk of stroke. Clinical Trail Registry National Institutes of Health(http: //www.clinicaltrials.gov), CT00262600.

Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial.

PubMed

Held, Claes; Hylek, Elaine M; Alexander, John H; Hanna, Michael; Lopes, Renato D; Wojdyla, Daniel M; Thomas, Laine; Al-Khalidi, Hussein; Alings, Marco; Xavier, Dennis; Ansell, Jack; Goto, Shinya; Ruzyllo, Witold; Rosenqvist, Mårten; Verheugt, Freek W A; Zhu, Jun; Granger, Christopher B; Wallentin, Lars

2015-05-21

In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban. Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI. Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

The risk of carotid artery stenting compared with carotid endarterectomy is greatest in patients treated within 7 days of symptoms.

PubMed

Rantner, Barbara; Goebel, Georg; Bonati, Leo H; Ringleb, Peter A; Mas, Jean-Louis; Fraedrich, Gustav

2013-03-01

Among patients with symptomatic carotid artery stenosis, carotid artery stenting (CAS) is associated with a higher risk of periprocedural stroke or death than carotid endarterectomy (CEA). Uncertainty remains whether the balance of risk changes with time since the most recent ischemic event. We investigated the association of time between the qualifying ischemic event and treatment (0-7 days, 8-14 days, and >14 days) with the risk of stroke or death within 30 days after CAS or CEA in a pooled analysis of data from individual patients randomized in the Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and the International Carotid Stenting Study (ICSS). Data were analyzed with a fixed-effect binomial regression model adjusted for source trial. Information on time of qualifying event was available for 2839 patients. In the first 30 days after intervention, any stroke or death occurred significantly more often in the CAS group (110/1434 [7.7%]) compared with the CEA group (54/1405 [3.8%]; crude risk ratio, 2.0; 95% confidence interval, 1.5-2.7). Patients undergoing CEA within the first 7 days of the qualifying event had the lowest periprocedural stroke or death rate (3/106 [2.8%]). Patients treated with CAS in the same period had a 9.4% risk of periprocedural stroke or death (13/138; risk ratio CAS vs CEA: 3.4; 95% confidence interval, 1.01-11.8; adjusted for age, sex, and type of qualifying event). Patients treated between 8 and 14 days showed a periprocedural stroke or death rate of 3.4% (7/208) and 8.1% (19/234), respectively, for CEA and CAS. The latest treatment group had 4% complications in the CEA group (44/1091) and 7.3% in the CAS group (78/1062). The increase in risk of CAS compared with CEA appears to be greatest in patients treated within 7 days of symptoms. Early surgery might remain most effective in stroke prevention in patients with symptomatic carotid artery stenosis. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

The Effects of Delirium Prevention Guidelines on Elderly Stroke Patients.

PubMed

Song, Jihye; Lee, Minkyung; Jung, Dukyoo

2017-07-01

This study aimed to evaluate the effectiveness of the delirium prevention interventions recommended by the Delirium Prevention Guidelines for Elderly Stroke Patients (DPGESP). The DPGESP comprises nine dimensions with 28 interventions, including risk factor assessment, orientation disorder prevention, sleeping pattern maintenance, sensory interventions, constipation, dehydration, hypoxia and infection prevention, pain management, and appropriate nutrition maintenance. This quasi-experimental study used a nonequivalent control group and a pretest-posttest design. The experimental and control groups each included 54 patients, and the participants were elderly patients who were admitted to the stroke unit. The study outcomes were the delirium incidence and severity, stroke impact, and length of hospitalization. Posttest values for delirium incidence, severity, stroke impact, and length of hospitalization were significantly improved in the experimental group. Implementation of the DPGESP had beneficial effects on the delirium incidence and severity, stroke impact, and length of hospitalization among elderly patients admitted to a stroke unit.

Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Asian Patients With Nonvalvular Atrial Fibrillation: Meta-Analysis.

PubMed

Wang, Kang-Ling; Lip, Gregory Y H; Lin, Shing-Jong; Chiang, Chern-En

2015-09-01

The use of vitamin K antagonists (VKAs), the cornerstone treatment for stroke prevention in patients with atrial fibrillation, is limited by the perceived risk of serious bleeding in Asia. Non-VKA oral anticoagulants (NOACs) are safer alternatives. Here, we evaluate performance differences of NOACs between Asians and non-Asians. We compared efficacy and safety of NOACs between patients enrolled in Asian and non-Asian countries using aggregative data from phase III clinical trials. The odds ratios (ORs [95% confidence interval]) were calculated by a random effects model. Comparing with VKAs, standard-dose NOACs reduced stroke or systemic embolism (OR=0.65 [0.52-0.83] versus 0.85 [0.77-0.93], P interaction= 0.045) more in Asians than in non-Asians and were safer in Asians than in non-Asians about major bleeding (OR=0.57 [0.44-0.74] versus 0.89 [0.76-1.04], P interaction=0.004), hemorrhagic stroke (OR=0.32 [0.19-0.52] versus 0.56 [0.44-0.70], P interaction=0.046) in particular, whereas gastrointestinal bleeding was significantly increased in non-Asians (OR=0.79 [0.48-1.32] versus 1.44 [1.12-1.85], P interaction=0.041). Generally, low-dose NOACs were safer than VKAs without heterogeneity in efficacy and safety between Asians and non-Asians, except for ischemic stroke, major, and gastrointestinal bleeding. Our findings suggest that standard-dose NOACs were more effective and safer in Asians than in non-Asians, whereas low-dose NOACs performed similarly in both populations. © 2015 The Authors.

Under-prescribing of Prevention Drugs and Primary Prevention of Stroke and Transient Ischaemic Attack in UK General Practice: A Retrospective Analysis.

PubMed

Turner, Grace M; Calvert, Melanie; Feltham, Max G; Ryan, Ronan; Fitzmaurice, David; Cheng, K K; Marshall, Tom

2016-11-01

Stroke is a leading cause of death and disability; worldwide it is estimated that 16.9 million people have a first stroke each year. Lipid-lowering, anticoagulant, and antihypertensive drugs can prevent strokes, but may be underused. We analysed anonymised electronic primary care records from a United Kingdom (UK) primary care database that covers approximately 6% of the UK population. Patients with first-ever stroke/transient ischaemic attack (TIA), ≥18 y, with diagnosis between 1 January 2009 and 31 December 2013, were included. Drugs were considered under-prescribed when lipid-lowering, anticoagulant, or antihypertensive drugs were clinically indicated but were not prescribed prior to the time of stroke or TIA. The proportions of strokes or TIAs with prevention drugs under-prescribed, when clinically indicated, were calculated. In all, 29,043 stroke/TIA patients met the inclusion criteria; 17,680 had ≥1 prevention drug clinically indicated: 16,028 had lipid-lowering drugs indicated, 3,194 anticoagulant drugs, and 7,008 antihypertensive drugs. At least one prevention drug was not prescribed when clinically indicated in 54% (9,579/17,680) of stroke/TIA patients: 49% (7,836/16,028) were not prescribed lipid-lowering drugs, 52% (1,647/3,194) were not prescribed anticoagulant drugs, and 25% (1,740/7,008) were not prescribed antihypertensive drugs. The limitations of our study are that our definition of under-prescribing of drugs for stroke/TIA prevention did not address patients' adherence to medication or medication targets, such as blood pressure levels. In our study, over half of people eligible for lipid-lowering, anticoagulant, or antihypertensive drugs were not prescribed them prior to first stroke/TIA. We estimate that approximately 12,000 first strokes could potentially be prevented annually in the UK through optimal prescribing of these drugs. Improving prescription of lipid-lowering, anticoagulant, and antihypertensive drugs is important to reduce the incidence and burden of stroke and TIA.

Stroke and Nutrition: A Review of Studies

PubMed Central

Foroughi, Mehdi; Akhavanzanjani, Mohsen; Maghsoudi, Zahra; Ghiasvand, Reza; Khorvash, Fariborz; Askari, Gholamreza

2013-01-01

Background: Stroke is one of the leading causes of death and certainly the major cause of disability in the world. Diet and nutrient has an effective role in prevention and control of the risk of stroke. The aim of this study was to review the studies on the relationship between dietary intake and stroke incidence. Methods: In this study, the terms of “Fat”, “cholesterol”, “antioxidant”, “vitamins”, “salt”, “potassium”, “calcium”, “carbohydrate”, “vegetables”, “fruits”, “meat”, “tea”, “whole grains”, “sugar-sweetened beverages”, “Mediterranean diet”, “dietary approaches to stop hypertension diet (DASH diet)”, “Western diet”, and “stroke” were searched in Pubmed search engine. The observational studies, cohort studies, clinical trial studies, systemic review, and meta-analysis reviews are also included in this study. Results: The study revealed that adherence to theimprovements in nutrition and diet canreducethe incidence ofstroke. Higher antioxidant, vitamins, potassium, calcium, vegetables, fruits, whole grain intake, and adherence to the Mediterranean dietor DASH diet can lower stroke incidence. Conclusions: Adherence to Mediterranean diet or DASH diet and increasing the consumption of antioxidant, vitamins, potassium, calcium food sources, vegetables, fruits, and whole grains intake can lower the risk of stroke. Healthy diet is effective in reducing risk of stroke, however, more studies need to be carried out in this area. PMID:23776719

How a Stroke Is Diagnosed

MedlinePlus

... Trials News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis ... UT Southwestern Medical Center. Copyright © 1997-2018 - The Internet Stroke Center. All rights reserved. The information contained ...

Stress reduction in the secondary prevention of cardiovascular disease: randomized, controlled trial of transcendental meditation and health education in Blacks.

PubMed

Schneider, Robert H; Grim, Clarence E; Rainforth, Maxwell V; Kotchen, Theodore; Nidich, Sanford I; Gaylord-King, Carolyn; Salerno, John W; Kotchen, Jane Morley; Alexander, Charles N

2012-11-01

Blacks have disproportionately high rates of cardiovascular disease. Psychosocial stress may contribute to this disparity. Previous trials on stress reduction with the Transcendental Meditation (TM) program have reported improvements in cardiovascular disease risk factors, surrogate end points, and mortality in blacks and other populations. This was a randomized, controlled trial of 201 black men and women with coronary heart disease who were randomized to the TM program or health education. The primary end point was the composite of all-cause mortality, myocardial infarction, or stroke. Secondary end points included the composite of cardiovascular mortality, revascularizations, and cardiovascular hospitalizations; blood pressure; psychosocial stress factors; and lifestyle behaviors. During an average follow-up of 5.4 years, there was a 48% risk reduction in the primary end point in the TM group (hazard ratio, 0.52; 95% confidence interval, 0.29-0.92; P=0.025). The TM group also showed a 24% risk reduction in the secondary end point (hazard ratio, 0.76; 95% confidence interval, 0.51-0.1.13; P=0.17). There were reductions of 4.9 mmHg in systolic blood pressure (95% confidence interval -8.3 to -1.5 mmHg; P=0.01) and anger expression (P<0.05 for all scales). Adherence was associated with survival. A selected mind-body intervention, the TM program, significantly reduced risk for mortality, myocardial infarction, and stroke in coronary heart disease patients. These changes were associated with lower blood pressure and psychosocial stress factors. Therefore, this practice may be clinically useful in the secondary prevention of cardiovascular disease. Clinical Trial Registration- URL: www.clinicaltrials.gov Unique identifier: NCT01299935.

Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery.

PubMed

Arsenault, Kyle A; Yusuf, Arif M; Crystal, Eugene; Healey, Jeff S; Morillo, Carlos A; Nair, Girish M; Whitlock, Richard P

2013-01-31

Atrial fibrillation is a common post-operative complication of cardiac surgery and is associated with an increased risk of post-operative stroke, increased length of intensive care unit and hospital stays, healthcare costs and mortality. Numerous trials have evaluated various pharmacological and non-pharmacological prophylactic interventions for their efficacy in preventing post-operative atrial fibrillation. We conducted an update to a 2004 Cochrane systematic review and meta-analysis of the literature to gain a better understanding of the effectiveness of these interventions. The primary objective was to assess the effects of pharmacological and non-pharmacological interventions for preventing post-operative atrial fibrillation or supraventricular tachycardia after cardiac surgery. Secondary objectives were to determine the effects on post-operative stroke or cerebrovascular accident, mortality, cardiovascular mortality, length of hospital stay and cost of treatment during the hospital stay. We searched the Cochrane Central Register of ControlLed Trials (CENTRAL) (Issue 8, 2011), MEDLINE (from 1946 to July 2011), EMBASE (from 1974 to July 2011) and CINAHL (from 1981 to July 2011). We selected randomized controlled trials (RCTs) that included adult patients undergoing cardiac surgery who were allocated to pharmacological or non-pharmacological interventions for the prevention of post-operative atrial fibrillation or supraventricular tachycardia, except digoxin, potassium (K(+)), or steroids. Two review authors independently abstracted study data and assessed trial quality. One hundred and eighteen studies with 138 treatment groups and 17,364 participants were included in this review. Fifty-seven of these studies were included in the original version of this review while 61 were added, including 27 on interventions that were not considered in the original version. Interventions included amiodarone, beta-blockers, sotalol, magnesium, atrial pacing and posterior pericardiotomy. Each of the studied interventions significantly reduced the rate of post-operative atrial fibrillation after cardiac surgery compared with a control. Beta-blockers (odds ratio (OR) 0.33; 95% confidence interval) CI 0.26 to 0.43; I(2) = 55%) and sotalol (OR 0.34; 95% CI 0.26 to 0.43; I(2) = 3%) appear to have similar efficacy while magnesium's efficacy (OR 0.55; 95% CI 0.41 to 0.73; I(2) = 51%) may be slightly less. Amiodarone (OR 0.43; 95% CI 0.34 to 0.54; I(2) = 63%), atrial pacing (OR 0.47; 95% CI 0.36 to 0.61; I(2) = 50%) and posterior pericardiotomy (OR 0.35; 95% CI 0.18 to 0.67; I(2) = 66%) were all found to be effective. Prophylactic intervention decreased the hospital length of stay by approximately two-thirds of a day and decreased the cost of hospital treatment by roughly $1250 US. Intervention was also found to reduce the odds of post-operative stroke, though this reduction did not reach statistical significance (OR 0.69; 95% CI 0.47 to 1.01; I(2) = 0%). No significant effect on all-cause or cardiovascular mortality was demonstrated. Prophylaxis to prevent atrial fibrillation after cardiac surgery with any of the studied pharmacological or non-pharmacological interventions may be favored because of its reduction in the rate of atrial fibrillation, decrease in the length of stay and cost of hospital treatment and a possible decrease in the rate of stroke. However, this review is limited by the quality of the available data and heterogeneity between the included studies. Selection of appropriate interventions may depend on the individual patient situation and should take into consideration adverse effects and the cost associated with each approach.

Acupuncture for acute stroke: study protocol for a multicenter, randomized, controlled trial.

PubMed

Chen, Lifang; Fang, Jianqiao; Ma, Ruijie; Froym, Ronen; Gu, Xudong; Li, Jianhua; Chen, Lina; Xu, Shouyu; Ji, Conghua

2014-06-08

Acupuncture has been widely used as a treatment for stroke in China for more than 3,000 years. However, previous research has not yet shown that acupuncture is effective as a stroke treatment. We report a protocol for a multicenter, randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on acute ischemic stroke. In a prospective trial involving three hospitals in the Zhejiang Province (China) 250 patients with a recent (less than 1 week previous) episode of ischemic stroke will be included. Patients will be randomized into two groups: an acupuncture group given scalp acupuncture and electroacupuncture, and a control group given no acupuncture. Eighteen treatment sessions will be performed over a three-week period. The primary outcome will be measured by changes in the National Institutes of Health Stroke Scale score at the one, three, and four-week follow-up. Secondary outcome measures will be: 1) the Fugl-Meyer assessment scale for motor function; 2) the mini-mental state examination and Montreal cognitive assessment for cognitive function; 3) the video-fluoroscopic swallowing study for swallowing ability; and 4) the incidence of adverse events. This trial is expected to clarify whether or not acupuncture is effective for acute stroke. It will also show if acupuncture can improve motor, cognitive, or swallowing function. Chinese Clinical Trial Registry ChiCTR-TRC-12001971.

Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

PubMed

Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

2012-01-01

The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

Cost-effectiveness of dabigatran etexilate in the prevention of stroke and systemic embolism in patients with atrial fibrillation in Belgium.

PubMed

Wouters, Hanne; Thijs, Vincent; Annemans, Lieven

2013-01-01

To assess the cost-effectiveness of dabigatran etexilate ('dabigatran') vs vitamin K antagonists (VKAs) in the Belgian healthcare setting for the prevention of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (AF). A Markov model was used to calculate the cost-effectiveness of dabigatran vs VKAs in Belgium, whereby warfarin was considered representative for the VKA class. Efficacy and safety data were taken from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial and a network meta-analysis. Local resource use and unit costs were included in the model. Effectiveness was expressed in Quality Adjusted Life-Years (QALYs). The model outcomes were total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). The level of International Normalized Ratio (INR) control and the use of other antithrombotic therapies observed in Belgian clinical practice were reflected in two scenario analyses. In the base case analysis, total costs per patient were €13,333 for dabigatran and €12,454 for warfarin. Total QALYs per patient were 9.51 for dabigatran and 9.19 for warfarin. The corresponding ICER was €2807/QALY. The ICER of dabigatran was €970/QALY vs warfarin with real-world INR control and €5296/QALY vs a mix of warfarin, aspirin, and no treatment. Results were shown to be robust in one-way and probabilistic sensitivity analyses. The analysis does not include long-term costs for clinical events, as these data were not available for Belgium. As in any economic model based on data from a randomized clinical trial, several assumptions had to be made when extrapolating results to routine clinical practice in Belgium. This analysis suggests that dabigatran, a novel oral anticoagulant, is a cost-effective treatment for the prevention of stroke and SE in patients with non-valvular AF in the Belgian healthcare setting.

Relationship between Risk Factor Control and Compliance with a Lifestyle Modification Program in the Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis Trial.

PubMed

Turan, Tanya N; Al Kasab, Sami; Nizam, Azhar; Lynn, Michael J; Harrell, Jamie; Derdeyn, Colin P; Fiorella, David; Janis, L Scott; Lane, Bethany F; Montgomery, Jean; Chimowitz, Marc I

2018-03-01

Lifestyle modification programs have improved the achievement of risk factor targets in a variety of clinical settings, including patients who have previously suffered a stroke or transient ischemic attack and those with multiple risk factors. Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) was the first vascular disease prevention trial to provide a commercially available lifestyle modification program to enhance risk factor control. We sought to determine the relationship between compliance with this program and risk factor control in SAMMPRIS. SAMMPRIS aggressive medical management included a telephonic lifestyle modification program provided free of charge to all subjects (n = 451) during their participation in the study. Subjects with fewer than 3 expected lifestyle-coaching calls were excluded from these analyses. Compliant subjects (n = 201) had  greater than or equal to 78.5% of calls (median % of completed/expected calls). Noncompliant subjects (n = 200) had less than 78.5% of calls or refused to participate. Mean risk factor values or % in-target for each risk factor was compared between compliant versus noncompliant subjects, using t tests and chi-square tests. Risk factor changes from baseline to follow-up were compared between the groups to account for baseline differences. Compliant subjects had better risk factor control throughout follow-up for low-density lipoprotein, systolic blood pressure (SBP), hemoglobin A1c (HgA1c), non-high-density lipoprotein, nonsmoking, and exercise than noncompliant subjects, but there was no difference for body mass index. After adjusting for baseline differences between the groups, compliant subjects had a greater change from baseline than noncompliant subjects for SBP did at 24 months and HgA1c at 6 months. SAMMPRIS subjects who were compliant with the lifestyle modification program had better risk factor control during the study for almost all risk factors. Published by Elsevier Inc.

Stroke survivors' endorsement of a "stress belief model" of stroke prevention predicts control of risk factors for recurrent stroke.

PubMed

Phillips, L Alison; Tuhrim, Stanley; Kronish, Ian M; Horowitz, Carol R

2014-01-01

Perceptions that stress causes and stress-reduction controls hypertension have been associated with poorer blood pressure (BP) control in hypertension populations. The current study investigated these "stress-model perceptions" in stroke survivors regarding prevention of recurrent stroke and the influence of these perceptions on patients' stroke risk factor control. Stroke and transient ischemic attack survivors (N=600) participated in an in-person interview in which they were asked about their beliefs regarding control of future stroke; BP and cholesterol were measured directly after the interview. Counter to expectations, patients who endorsed a "stress-model" but not a "medication-model" of stroke prevention were in better control of their stroke risk factors (BP and cholesterol) than those who endorsed a medication-model but not a stress-model of stroke prevention (OR for poor control=.54, Wald statistic=6.07, p=.01). This result was not explained by between group differences in patients' reported medication adherence. The results have implications for theory and practice, regarding the role of stress belief models and acute cardiac events, compared to chronic hypertension.

Implementing a complex rehabilitation intervention in a stroke trial: a qualitative process evaluation of AVERT.

PubMed

Luker, Julie A; Craig, Louise E; Bennett, Leanne; Ellery, Fiona; Langhorne, Peter; Wu, Olivia; Bernhardt, Julie

2016-05-10

The implementation of multidisciplinary stroke rehabilitation interventions is challenging, even when the intervention is evidence-based. Very little is known about the implementation of complex interventions in rehabilitation clinical trials. The aim of study was to better understand how the implementation of a rehabilitation intervention in a clinical trial within acute stroke units is experienced by the staff involved. This qualitative process evaluation was part of a large Phase III stroke rehabilitation trial (AVERT). A descriptive qualitative approach was used. We purposively sampled 53 allied health and nursing staff from 19 acute stroke units in Australia, New Zealand and Scotland. Semi-structured interviews were conducted by phone, voice-internet, or face to face. Digitally recorded interviews were transcribed and analysed by two researchers using rigorous thematic analysis. Our analysis uncovered ten important themes that provide insight into the challenges of implementing complex new rehabilitation practices within complex care settings, plus factors and strategies that assisted implementation. Themes were grouped into three main categories: staff experience of implementing the trial intervention, barriers to implementation, and overcoming the barriers. Participation in the trial was challenging but had personal rewards and improved teamwork at some sites. Over the years that the trial ran some staff perceived a change in usual care. Barriers to trial implementation at some sites included poor teamwork, inadequate staffing, various organisational barriers, staff attitudes and beliefs, and patient-related barriers. Participants described successful implementation strategies that were built on interdisciplinary teamwork, education and strong leadership to 'get staff on board', and developing different ways of working. The AVERT stroke rehabilitation trial required commitment to deliver an intervention that needed strong collaboration between nurses and physiotherapists and was different to current care models. This qualitative process evaluation contributes unique insights into factors that may be critical to successful trials teams, and as AVERT was a pragmatic trial, success factors to delivering complex intervention in clinical practice. AVERT registered with Australian New Zealand Clinical Trials Registry ACTRN12606000185561 .

Prevention of ischemic stroke in clinical practice: a role of internists and general practitioners.

PubMed

Niewada, Maciej; Członkowska, Anna

2014-01-01

Stroke constitutes a substantial clinical and socio-economic burden. It is currently the third cause of death worldwide and results in mortality or disability in every third patient at the end of the first year following an acute cerebrovascular event. Although in-hospital mortality rates in stroke patients have decreased, prevention and cardiovascular risk control remain critical for improving the prognosis and reducing stroke burden worldwide. The definitions of stroke and transient ischemic attack (TIA) have been recently modified following the findings from neuroimaging and thrombolysis research. Both stroke and TIA are recurrent and preventable disorders. Both patients with stroke and those with TIA require prompt clinical workup, risk assessment, and appropriate management because the risk of recurrence, stroke, and coronary events is significant. The 5 most common cardiovascular risk factors (high blood pressure, smoking, abdominal obesity, diet, and lack of physical activity) are responsible for 80% of the cases. Stroke prevention involves lifestyle modification and specific treatment. Secondary prevention of ischemic stroke involves early treatment (antiplatelets and carotid interventions) and long-term management including lifestyle changes, antihypertensive therapy, antiplatelets, antithrombotic drugs in patients with atrial fibrillation, and the use of statins and other lipid-lowering drugs. Stroke patients are at risk of depression, dementia, epilepsy, and other complications that also require targeted treatment.

Frequency, Risk Factors, and Outcome of Coexistent Small Vessel Disease and Intracranial Arterial Stenosis: Results From the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial.

PubMed

Kwon, Hyung-Min; Lynn, Michael J; Turan, Tanya N; Derdeyn, Colin P; Fiorella, David; Lane, Bethany F; Montgomery, Jean; Janis, L Scott; Rumboldt, Zoran; Chimowitz, Marc I

2016-01-01

Intracranial arterial stenosis (ICAS) and small vessel disease (SVD) may coexist. There are limited data on the frequency and risk factors for coexistent SVD and the effect of SVD on stroke recurrence in patients receiving medical treatment for ICAS. To investigate the frequency and risk factors for SVD and the effect of SVD on stroke recurrence in patients with ICAS. A post hoc analysis of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study, a prospective, multicenter clinical trial. Among 451 participants, 313 (69.4%) had baseline brain magnetic resonance imaging scans read centrally for SVD that was defined by any of the following: old lacunar infarction, grade 2 to 3 on the Fazekas scale (for high-grade white matter hyperintensities), or microbleeds. Patient enrollment in SAMMPRIS began November 25, 2008, and follow-up ended on April 30, 2013. Data analysis for the present study was performed from May 13, 2014, to July 29, 2015. Risk factors in patients with vs without SVD and the association between SVD and other baseline risk factors with any ischemic stroke and ischemic stroke in the territory of the stenotic artery determined using proportional hazards regression. Of 313 patients, 155 individuals (49.5%) had SVD noted on baseline magnetic resonance imaging. Variables that were significantly higher in patients with SVD, reported as mean (SD), included age, 63.5 (10.5) years (P < .001), systolic blood pressure, 149 (22) mm Hg (P < .001), glucose level, 130 (50) mg/dL (P = .03), and lower Montreal Cognitive Assessment scores (median, ≥24 [interquartile range, 20-26]; P = .02).Other significant variables were the number of patients with diabetes mellitus (88 of 155 [56.8%]; P = .003), coronary artery disease (46 [29.7%]; P = .004), stroke before the qualifying event (59 [38.1%]; P < .001), old infarct in the territory of the stenotic intracranial artery (88 [56.8%]; P < .001), and receiving antithrombotic therapy at the time of the qualifying event (109 [70.3%]; P = .005). The association between SVD and any ischemic stroke was nearly significant in the direction of a higher risk (18 [23.7%]); P = .07) for patients with SVD. On bivariate analysis, SVD was not associated with an increased risk on multivariable analyses (hazard ratio, 1.7 [95% CI, 0.8-3.8]; P = .20). In addition, SVD was not associated with an increased risk of stroke in the territory on either bivariate or multivariable analyses. Although SVD is common in patients with ICAS, the presence of SVD on baseline magnetic resonance imaging is not independently associated with an increased risk of stroke in patients with ICAS. clinicaltrials.gov Identifier: NCT00576693.

Acupuncture for stroke rehabilitation.

PubMed

Yang, Ai; Wu, Hong Mei; Tang, Jin-Ling; Xu, Li; Yang, Ming; Liu, Guan J

2016-08-26

Stroke is the second most common cause of death in the world and in China it has now become the main cause of death. It is also a main cause of adult disability and dependency. Acupuncture for stroke has been used in China for hundreds of years and is increasingly practiced in some Western countries. This is an update of the Cochrane review originally published in 2006 . To determine the efficacy and safety of acupuncture therapy in people with subacute and chronic stroke. We intended to test the following hypotheses: 1) acupuncture can reduce the risk of death or dependency in people with subacute and chronic stroke at the end of treatment and at follow-up; 2) acupuncture can improve neurological deficit and quality of life after treatment and at the end of follow-up; 3) acupuncture can reduce the number of people requiring institutional care; and 4) acupuncture is not associated with any intolerable adverse effects. We searched the Cochrane Stroke Group Trials Register (June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library 2015, Issue 7), MEDLINE (1966 to July 2015, Ovid), EMBASE (1980 to July 2015, Ovid), CINAHL (1982 to July 2015, EBSCO), and AMED (1985 to July 2015, Ovid). We also searched the following four Chinese medical databases: China Biological Medicine Database (July 2015); Chinese Science and Technique Journals Database (July 2015); China National Infrastructure (July 2015), and Wan Fang database (July 2015). Truly randomised unconfounded clinical trials among people with ischaemic or haemorrhagic stroke, in the subacute or chronic stage, comparing acupuncture involving needling with placebo acupuncture, sham acupuncture, or no acupuncture. Two review authors independently selected trials for inclusion, assessed quality, extracted and cross-checked the data. We included 31 trials with a total of 2257 participants in the subacute or chronic stages of stroke. The methodological quality of most of the included trials was not high. The quality of evidence for the main outcomes was low or very low based on the assessment by the system of Grades of Recommendation, Assessment, Development and Evaluation (GRADE).Two trials compared real acupuncture plus baseline treatment with sham acupuncture plus baseline treatment. There was no evidence of differences in the changes of motor function and quality of life between real acupuncture and sham acupuncture for people with stroke in the convalescent stage.Twenty-nine trials compared acupuncture plus baseline treatment versus baseline treatment alone. Compared with no acupuncture, for people with stroke in the convalescent phase, acupuncture had beneficial effects on the improvement of dependency (activity of daily living) measured by Barthel Index (nine trials, 616 participants; mean difference (MD) 9.19, 95% confidence interval (CI) 4.34 to 14.05; GRADE very low), global neurological deficiency (seven trials, 543 participants; odds ratio (OR) 3.89, 95% CI 1.78 to 8.49; GRADE low), and specific neurological impairments including motor function measured by Fugl-Meyer Assessment (four trials, 245 participants; MD 6.16, 95% CI 4.20 to 8.11; GRADE low), cognitive function measured by the Mini-Mental State Examination (five trials, 278 participants; MD 2.54, 95% CI 0.03 to 5.05; GRADE very low), depression measured by the Hamilton Depression Scale (six trials, 552 participants; MD -2.58, 95% CI -3.28 to -1.87; GRADE very low), swallowing function measured by drinking test (two trials, 200 participants; MD -1.11, 95% CI -2.08 to -0.14; GRADE very low), and pain measured by the Visual Analogue Scale (two trials, 118 participants; MD -2.88, 95% CI -3.68 to -2.09; GRADE low). Sickness caused by acupuncture and intolerance of pain at acupoints were reported in a few participants with stroke in the acupuncture groups. No data on death, the proportion of people requiring institutional care or requiring extensive family support, and all-cause mortality were available in all included trials. From the available evidence, acupuncture may have beneficial effects on improving dependency, global neurological deficiency, and some specific neurological impairments for people with stroke in the convalescent stage, with no obvious serious adverse events. However, most included trials were of inadequate quality and size. There is, therefore, inadequate evidence to draw any conclusions about its routine use. Rigorously designed, randomised, multi-centre, large sample trials of acupuncture for stroke are needed to further assess its effects.

Omega-3 polyunsaturated fatty acids for the prevention of cardiovascular disease: do formulation, dosage & comparator matter?

PubMed

DiNicolantonio, James J; Meier, Pascal; O'Keefe, James H

2013-01-01

Multiple trials over the past two decades testing omega-3 polyunsaturated fatty acids (PUFAs), containing eicosapentaenoic acid (EPA) and or docosahexaenoic acid (DHA), have shown substantial benefits for reducing major coronary heart disease (CHD) events, all-cause mortality, cardiovascular (CV) death, sudden cardiac death (SCD), and stroke. However, recent trials testing omega-3s have generally failed to confirm these benefits. While increased fish and fish oil intake among the general population, increased use of optimal medical therapy (including statins, aspirin, and modern antihypertensive medications) probably make it more challenging for fish oil supplementation to show additional benefits, there might be further explanations in the formulation, dosage, and comparator used in these recent omega-3 trials.

General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial.

PubMed

Lewis, S C; Warlow, C P; Bodenham, A R; Colam, B; Rothwell, P M; Torgerson, D; Dellagrammaticas, D; Horrocks, M; Liapis, C; Banning, A P; Gough, M; Gough, M J

2008-12-20

The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. The Health Foundation (UK) and European Society of Vascular Surgery.

From prevention to nursing home care: a comprehensive national audit of stroke care.

PubMed

Horgan, Frances; McGee, Hannah; Hickey, Anne; Whitford, David L; Murphy, Sean; Royston, Maeve; Cowman, Seamus; Shelley, Emer; Conroy, Ronan M; Wiley, Miriam; O'Neill, Desmond

2011-01-01

Many countries are developing national audits of stroke care. However, these typically focus on stroke care from acute event to hospital discharge rather than the full spectrum from prevention to long-term care. We report on a comprehensive national audit of stroke care in the community and hospitals in the Republic of Ireland. The findings provide insights into the wider needs of people with stroke and their families, a basis for developing stroke-appropriate health strategies, and a global model for the evaluation of stroke services. Six national surveys were completed: general practitioners (prevention and primary care), hospital organisational and clinical audit of 2,570 consecutive stroke admissions (acute and hospital care), allied health professionals and public health nurses (discharge to community care), nursing homes (needs of patients discharged to long-term care), and patient and carers (post-hospital phase of rehabilitation and ongoing care). The audit identified substantial deficits in a number of areas including primary prevention, emergency assessment/investigation and treatment in hospital, discharge planning, rehabilitation and ongoing secondary prevention, and communication with patients and families. There was a lack of coordination and communication between the acute and community services, with a dearth of therapy services in both home and nursing home settings. This multi-faceted national stroke audit facilitated multiple perspectives on the continuum of stroke prevention and care. An overall synthesis of surveys supports the development of a multidisciplinary perspective in planning the development of comprehensive stroke services at the national level, and may assist in regional and global development of stroke strategies. Copyright © 2011 S. Karger AG, Basel.

Reducing stroke in women with risk factor management: blood pressure and cholesterol.

PubMed

Baghshomali, Sanam; Bushnell, Cheryl

2014-09-01

Stroke is a major cause of death and disability in adults worldwide. Prevention focused on modifiable risk factors, such as hypertension and hyperlipidemia, has shown them to be of significant importance in decreasing the risk of stroke. Multiple studies have brought to light the differences between men and women with regards to stroke and these risk factors. Women have a higher prevalence of stroke, mortality and disability and it has been shown that preventive and treatment options are not as comprehensive for women. Hence, it is of great necessity to evaluate and summarize the differences in gender and stroke risk factors in order to target disparities and optimize prevention, especially because women have a higher lifetime risk of stroke. The purpose of this review is to summarize sex differences in the prevalence of hypertension and hyperlipidemia. In addition, we will review the sex differences in stroke prevention effectiveness and adherence to blood pressure and cholesterol medications, and suggest future directions for research to reduce the burden of stroke in women.

Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease.

PubMed

Kimachi, Miho; Furukawa, Toshi A; Kimachi, Kimihiko; Goto, Yoshihito; Fukuma, Shingo; Fukuhara, Shunichi

2017-11-06

Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin. To assess the efficacy and safety of DOAC including apixaban, dabigatran, edoxaban, and rivaroxaban versus warfarin among AF patients with CKD. We searched the Cochrane Kidney and Transplant Specialised Register (up to 1 August 2017) through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. We included all randomised controlled trials (RCTs) which directly compared the efficacy and safety of direct oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) with dose-adjusted warfarin for preventing stroke and systemic embolic events in non-valvular AF patients with CKD, defined as creatinine clearance (CrCl) or eGFR between 15 and 60 mL/min (CKD stage G3 and G4). Two review authors independently selected studies, assessed quality, and extracted data. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for the association between anticoagulant therapy and all strokes and systemic embolic events as the primary efficacy outcome and major bleeding events as the primary safety outcome. Confidence in the evidence was assessing using GRADE. Our review included 12,545 AF participants with CKD from five studies. All participants were randomised to either DOAC (apixaban, dabigatran, edoxaban, and rivaroxaban) or dose-adjusted warfarin. Four studies used a central, interactive, automated response system for allocation concealment while the other did not specify concealment methods. Four studies were blinded while the other was partially open-label. However, given that all studies involved blinded evaluation of outcome events, we considered the risk of bias to be low. We were unable to create funnel plots due to the small number of studies, thwarting assessment of publication bias. Study duration ranged from 1.8 to 2.8 years. The large majority of participants included in this study were CKD stage G3 (12,155), and a small number were stage G4 (390). Of 12,545 participants from five studies, a total of 321 cases (2.56%) of the primary efficacy outcome occurred per year. Further, of 12,521 participants from five studies, a total of 617 cases (4.93%) of the primary safety outcome occurred per year. DOAC appeared to probably reduce the incidence of stroke and systemic embolism events (5 studies, 12,545 participants: RR 0.81, 95% CI 0.65 to 1.00; moderate certainty evidence) and to slightly reduce the incidence of major bleeding events (5 studies, 12,521 participants: RR 0.79, 95% CI 0.59 to 1.04; low certainty evidence) in comparison with warfarin. Our findings indicate that DOAC are as likely as warfarin to prevent all strokes and systemic embolic events without increasing risk of major bleeding events among AF patients with kidney impairment. These findings should encourage physicians to prescribe DOAC in AF patients with CKD without fear of bleeding. The major limitation is that the results of this study chiefly reflect CKD stage G3. Application of the results to CKD stage G4 patients requires additional investigation. Furthermore, we could not assess CKD stage G5 patients. Future reviews should assess participants at more advanced CKD stages. Additionally, we could not conduct detailed analyses of subgroups and sensitivity analyses due to lack of data.

A multilevel intervention to increase community hospital use of alteplase for acute stroke (INSTINCT): a cluster-randomised controlled trial.

PubMed

Scott, Phillip A; Meurer, William J; Frederiksen, Shirley M; Kalbfleisch, John D; Xu, Zhenzhen; Haan, Mary N; Silbergleit, Robert; Morgenstern, Lewis B

2013-02-01

Use of alteplase improves outcome in some patients with stroke. Several types of barrier frequently prevent its use. We assessed whether a standardised, barrier-assessment, multicomponent intervention could increase alteplase use in community hospitals in Michigan, USA. In a cluster-randomised controlled trial, we selected adult, non-specialty, acute-care community hospitals in the Lower Peninsula of Michigan, USA. Eligible hospitals discharged at least 100 patients who had had a stroke per year, had less than 100 000 visits to the emergency department per year, and were not academic comprehensive stroke centres. Using a computer-generated randomisation sequence, we selected 12 matched pairs of eligible hospitals. Within pairs, the hospitals were allocated to intervention or control groups with restricted randomisation in January, 2007. Between January, 2007, and December, 2007, intervention hospitals implemented a multicomponent intervention that included qualitative and quantitative assessment of barriers to alteplase use and ways to address the findings, and provided additional support. The primary outcome was change in alteplase use in patients with stroke in emergency departments between the pre-intervention period (January, 2005, to December, 2006) and the post-intervention period (January, 2008, to January, 2010). Physicians in participating hospitals and the coordinating centre could not be masked to group assignment, but were masked to progress made in paired control hospitals. External medical reviewers who were masked to group assignment assessed outcomes. We did intention-to-treat (ITT) and target-population (without one pair that was excluded after randomisation) analyses. This trial is registered at ClinicalTrials.gov, number NCT00349479. All 24 hospitals completed the study. Overall, 745 of 40 823 patients with stroke received intravenous alteplase treatment. In the ITT analysis, the proportion of patients with stroke who were admitted and treated with alteplase increased between the pre-intervention and post-intervention periods in intervention hospitals (89 [1·25%] of 7119 patients to 235 [2·79%] of 8419) to a greater extent than in control hospitals (99 [1·25%] of 7946 to 194 [2·10%] of 9222), but the difference between groups was not significant (relative risk [RR] 1·37, 95% CI 0·96-1·93; p=0·08). In the target-population analysis, the increase in alteplase use in intervention hospitals (59 [1·00%] of 5882 to 191 [2·62%] of 7288) was significantly greater than in control hospitals (65 [1·09%] of 5957 to 120 [1·72%] of 6989; RR 1·68, 95% CI 1·09-2·57; p=0·02), but was still clinically modest. The intervention did not significantly increase alteplase use in patients with ischaemic stroke. The increase in use of alteplase in the target population was significant, but smaller than the effect to which the study was powered. Additional strategies to increase acute stroke treatment are needed. National Institutes of Health National Institute of Neurological Disorders and Stroke. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimal combination treatment and vascular outcomes in recent ischemic stroke patients by premorbid risk level.

PubMed

Park, Jong-Ho; Ovbiagele, Bruce

2015-08-15

Optimal combination of secondary stroke prevention treatment including antihypertensives, antithrombotic agents, and lipid modifiers is associated with reduced recurrent vascular risk including stroke. It is unclear whether optimal combination treatment has a differential impact on stroke patients based on level of vascular risk. We analyzed a clinical trial dataset comprising 3680 recent non-cardioembolic stroke patients aged ≥35 years and followed for 2 years. Patients were categorized by appropriateness levels 0 to III depending on the number of the drugs prescribed divided by the number of drugs potentially indicated for each patient (0=none of the indicated medications prescribed and III=all indicated medications prescribed [optimal combination treatment]). High-risk was defined as having a history of stroke or coronary heart disease (CHD) prior to the index stroke event. Independent associations of medication appropriateness level with a major vascular event (stroke, CHD, or vascular death), ischemic stroke, and all-cause death were analyzed. Compared with level 0, for major vascular events, the HR of level III in the low-risk group was 0.51 (95% CI: 0.20-1.28) and 0.32 (0.14-0.70) in the high-risk group; for stroke, the HR of level III in the low-risk group was 0.54 (0.16-1.77) and 0.25 (0.08-0.85) in the high-risk group; and for all-cause death, the HR of level III in the low-risk group was 0.66 (0.09-5.00) and 0.22 (0.06-0.78) in the high-risk group. Optimal combination treatment is related to a significantly lower risk of future vascular events and death among high-risk patients after a recent non-cardioembolic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Ischemic Stroke: What Does the Histological Composition Tell Us About the Origin of the Thrombus?

PubMed

Sporns, Peter B; Hanning, Uta; Schwindt, Wolfram; Velasco, Aglaé; Minnerup, Jens; Zoubi, Tarek; Heindel, Walter; Jeibmann, Astrid; Niederstadt, Thomas Ulrich

2017-08-01

The introduction of stent retrievers allows for a complete extraction and histological analysis of human thrombi. Ischemic stroke is a major health issue, and differentiation of underlying causes is highly relevant to prevent recurrent stroke. Therefore, histopathologic analysis of the embolic clots after removal may provide valuable information about underlying pathologies. This study analyzes histological clot composition and aims to identify specific patterns that might help to distinguish causes of ischemic stroke. Patients with occlusion of the carotid-T or middle cerebral artery who underwent thrombectomy at our university medical center between December 2013 and February 2016 were included. Samples were histologically analyzed (hematoxylin and eosin, Elastica van Gieson, and Prussian blue), additionally immunohistochemistry for CD3, CD20, and CD68/KiM1P was performed. These data, along with additional clinical and interventional parameters, were compared for different stroke subtypes, as defined by the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. One hundred eighty-seven patients were included, of these, in 77 patients, cardioembolic; in 46 patients, noncardioembolic; and in 64 patients, cryptogenic pathogenesis was determined. Cardioembolic thrombi had higher proportions of fibrin/platelets ( P =0.027), less erythrocytes ( P =0.005), and more leucocytes ( P =0.026) than noncardioembolic thrombi. We observed a strong overlap of cryptogenic strokes and cardioembolic strokes concerning thrombus histology. The immunohistochemical parameters CD3, CD20, and CD68/KiM1P showed no statistically noticeable differences between stroke subtypes. Histological thrombus features vary significantly according to the underlying cause and may help to differentiate between cardioembolic and noncardioembolic stroke. In addition, our study supports the hypothesis that most cryptogenic strokes have a cardioembolic cause. © 2017 American Heart Association, Inc.