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.

Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study.

PubMed

Go, Alan S; Reynolds, Kristi; Yang, Jingrong; Gupta, Nigel; Lenane, Judith; Sung, Sue Hee; Harrison, Teresa N; Liu, Taylor I; Solomon, Matthew D

2018-05-16

Atrial fibrillation is a potent risk factor for stroke, but whether the burden of atrial fibrillation in patients with paroxysmal atrial fibrillation independently influences the risk of thromboembolism remains controversial. To determine if the burden of atrial fibrillation characterized using noninvasive, continuous ambulatory monitoring is associated with the risk of ischemic stroke or arterial thromboembolism in adults with paroxysmal atrial fibrillation. This retrospective cohort study conducted from October 2011 and October 2016 at 2 large integrated health care delivery systems used an extended continuous cardiac monitoring system to identify adults who were found to have paroxysmal atrial fibrillation on 14-day continuous ambulatory electrocardiographic monitoring. The burden of atrial fibrillation was defined as the percentage of analyzable wear time in atrial fibrillation or flutter during the up to 14-day monitoring period. Ischemic stroke and other arterial thromboembolic events occurring while patients were not taking anticoagulation were identified through November 2016 using electronic medical records and were validated by manual review. We evaluated the association of the burden of atrial fibrillation with thromboembolism while not taking anticoagulation after adjusting for the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) or CHA2DS2-VASc stroke risk scores. Among 1965 adults with paroxysmal atrial fibrillation, the mean (SD) age was 69 (11.8) years, 880 (45%) were women, 496 (25%) were persons of color, the median ATRIA stroke risk score was 4 (interquartile range [IQR], 2-7), and the median CHA2DS2-VASc score was 3 (IQR, 1-4). The median burden of atrial fibrillation was 4.4% (IQR ,1.1%-17.23%). Patients with a higher burden of atrial fibrillation were less likely to be women or of Hispanic ethnicity, but had more prior cardioversion attempts compared with those who had a lower burden. After adjusting for either ATRIA or CHA2DS2-VASc stroke risk scores, the highest tertile of atrial fibrillation burden (≥11.4%) was associated with a more than 3-fold higher adjusted rate of thromboembolism while not taking anticoagulants (adjusted hazard ratios, 3.13 [95% CI, 1.50-6.56] and 3.16 [95% CI, 1.51-6.62], respectively) compared with the combined lower 2 tertiles of atrial fibrillation burden. Results were consistent across demographic and clinical subgroups. A greater burden of atrial fibrillation is associated with a higher risk of ischemic stroke independent of known stroke risk factors in adults with paroxysmal atrial fibrillation.

Relations of Anticoagulant Therapy with Cognitive Impairment among Patients with Atrial Fibrillation: A Meta-Analysis and Systematic Review.

PubMed

Cheng, Wenke; Liu, Weijun; Li, Bin; Li, Dongfang

2018-03-02

Currently, it is considered that atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia, which is independent of stroke. However, the relationship between anticoagulant drugs and cognitive function in patients with atrial fibrillation is unknown. This study aimed to complete a meta-analysis, and investigate the association between Anticoagulant therapy and cognitive impairment in patients undergoing AF. Two investigators systematically searched the Cochrane Library, PubMed, Embase databases and Web of Science for all studies showing associations. Hazard ratios (HRs) were extracted and pooled. 8 studies included 471057 participants; TTR < 25% vs TTR> 75%; (HR 3.02, 95% CI 1.12-8.91; P=0.03); TTR 25-50% vs TTR> 75% (HR 2.44, 95% CI 0.95-6.22; P=0.06); TTR 50-75% vs TTR> 75% (HR 1.75, 95% CI 0.90-3.99; P=0.1); OAC vs No OAC (HR 0.71, 95% CI.69-0.74; P<0.00001) NOAC vs warfarin (HR0.51, 95% CI0.37-0.71; P<0.00001). Oral anticoagulants (OAC) significantly reduce the occurrence of cognitive impairment in patients with atrial fibrillation. Compared with warfarin, NOAC has an efficiently protective effect on cognition. In the range of INR2-3, with the increase of TTR, the incidence of cognitive impairment is lower.

Cost-Effectiveness of Oral Anticoagulants for Ischemic Stroke Prophylaxis Among Nonvalvular Atrial Fibrillation Patients.

PubMed

Shah, Anuj; Shewale, Anand; Hayes, Corey J; Martin, Bradley C

2016-06-01

The objective of the study is to compare the cost-effectiveness of oral anticoagulants among atrial fibrillation patients at an increased stroke risk. A Markov model was constructed to project the lifetime costs and quality-adjusted survival (QALYs) of oral anticoagulants using a private payer's perspective. The distribution of stroke risk (CHADS2 score: congestive heart failure, hypertension, advanced age, diabetes mellitus, stroke) and age of the modeled population was derived from a cohort of commercially insured patients with new-onset atrial fibrillation. Probabilities of treatment specific events were derived from published clinical trials. Event and downstream costs were determined from the cost of illness studies. Drug costs were obtained from 2015 National Average Drug Acquisition Cost data. In the base case analysis, warfarin was the least costly ($46 241; 95% CI, 44 499-47 874) and apixaban had the highest QALYs (9.38; 95% CI, 9.24-9.48 QALYs). Apixaban was found to be a cost-effective strategy over warfarin (incremental cost-effectiveness ratio=$25 816) and dominated other anticoagulants. Probabilistic sensitivity analysis showed that apixaban had at least a 61% chance of being the most cost-effective strategy at willingness to pay value of $100 000 per QALY. Among patients with CHADS2 ≥3, dabigatran was the dominant strategy. The model was sensitive to efficacy estimates of apixaban, dabigatran, and edoxaban and the cost of these drugs. All the newer oral anticoagulants compared were more effective than adjusted dosed warfarin. Our model showed that apixaban was the most effective anticoagulant in a general atrial fibrillation population and has an incremental cost-effectiveness ratio <$50 000/QALY. For those with higher stroke risk (CHADS2≥3), dabigatran was the most cost-effective treatment option. © 2016 American Heart Association, Inc.

Early cardioversion of atrial fibrillation and atrial flutter guided by transoesophageal echocardiography: a single centre 8.5-year experience.

PubMed

Corrado, G; Santarone, M; Beretta, S; Tadeo, G; Tagliagambe, L M; Foglia-Manzillo, G; Spata, M; Miglierina, E; Acquati, F; Santarone, M

2000-04-01

To analyse the safety and impact on maintenance of sinus rhythm of transoesophageal echocardiographically guided early cardioversion associated with short-term anticoagulation in a large series of patients with atrial fibrillation and atrial flutter. Patients who were candidates for cardioversion were eligible for inclusion if they had atrial fibrillation or atrial flutter lasting longer than 2 days or of unknown duration. Patients received short-term anticoagulation with warfarin or heparin and underwent transthoracic echocardiography followed by transoesophageal echocardiography. Early cardioversion was performed if no thrombus was seen on the transoesophageal study. Warfarin was maintained for 1 month after cardioversion. In patients with atrial thrombi, cardioversion was deferred and prolonged anticoagulation was prescribed. The study population included 183 patients. One hundred and sixty nine patients without atrial thrombi underwent early cardioversion. Fourteen patients with atrial thrombi (7.6%) underwent a second transoesophageal echocardiogram after a median of 4 weeks of oral warfarin, and cardioversion was performed if clot regression was documented. No patient in our study population had a clinical thromboembolic event at 1 month follow-up (95% C.I. 0-0.016). The immediate success rate of cardioversion was better among patients with atrial fibrillation < 4 weeks duration compared with patients with atrial fibrillation of longer or of unknown duration: 96.6% vs 85%, respectively (P = 0.014). At 1 month follow-up, the percentage of arrhythmia relapses in patients with initially successful cardioversion was similar in the two groups (29% vs 26%, P = ns); thus the initial better outcome in patients with recent-onset arrhythmia was not lost. Transoesophageal echocardiography-guided early cardioversion in concert with short-term anticoagulation is safe. This approach permits abbreviation of the overall duration of atrial fibrillation and has a better impact on the maintenance of sinus rhythm for patients in whom the duration of atrial fibrillation is < 4 weeks.

Stroke prevention in the elderly atrial fibrillation patient with comorbid conditions: focus on non-vitamin K antagonist oral anticoagulants

PubMed Central

Turagam, Mohit K; Velagapudi, Poonam; Flaker, Greg C

2015-01-01

Stroke prevention in elderly atrial fibrillation patients remains a challenge. There is a high risk of stroke and systemic thromboembolism but also a high risk of bleeding if anticoagulants are prescribed. The elderly have increased chronic kidney disease, coronary artery disease, polypharmacy, and overall frailty. For all these reasons, anticoagulant use is underutilized in the elderly. In this manuscript, the benefits of non-vitamin K antagonist oral anticoagulants compared with warfarin in the elderly patient population with multiple comorbid conditions are reviewed. PMID:26366064

Dental Procedures in Patients with Atrial Fibrillation and New Oral Anticoagulants

PubMed Central

2014-01-01

This review discusses the basic pharmacology of new oral anticoagulants that are used for prevention of thromboembolism in patients with atrial fibrillation. It presents available evidence, and provides recommendations for the management of patients requiring invasive procedures in dental practice. PMID:26835072

Ischemic Stroke Risk in Patients With Atrial Fibrillation and CHA2DS2-VASc Score of 1: Systematic Review and Meta-Analysis.

PubMed

Joundi, Raed A; Cipriano, Lauren E; Sposato, Luciano A; Saposnik, Gustavo

2016-05-01

The CHA2DS2-VASc score aims to improve risk stratification of ischemic stroke among patients with atrial fibrillation to identify those who can safely forego oral anticoagulation. Oral anticoagulation treatment guidelines remain uncertain for CHA2DS2-VASc score of 1. We conducted a systematic review and meta-analysis of the risk of ischemic stroke for patients with atrial fibrillation and CHA2DS2-VASc score of 0, 1, or 2 not treated with oral anticoagulation. We searched MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from the start of the database up until April 15, 2015. We included studies that stratified the risk of ischemic stroke by CHA2DS2-VASc score for patients with nonvalvular atrial fibrillation. We estimated the summary annual rate of ischemic stroke using random effects meta-analyses and compared the estimated stroke rates with published net-benefit thresholds for initiating anticoagulants. 1162 abstracts were retrieved, of which 10 met all inclusion criteria for the study. There was substantial heterogeneity among studies. The summary estimate for the annual risk of ischemic stroke was 1.61% (95% confidence interval 0%-3.23%) for CHA2DS2-VASc score of 1, meeting the theoretical threshold for using novel oral anticoagulants (0.9%), but below the threshold for warfarin (1.7%). The summary incident risk of ischemic stroke was 0.68% (95% confidence interval 0.12%-1.23%) for CHA2DS2-VASc score of 0 and 2.49% (95% confidence interval 1.16%-3.83%) for CHA2DS2-VASc score of 2. Our meta-analysis of ischemic stroke risk in atrial fibrillation patients suggests that those with CHA2DS2-VASc score of 1 may be considered for a novel oral anticoagulant, but because of high heterogeneity, the decision should be based on individual patient characteristics. © 2016 American Heart Association, Inc.

Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation.

PubMed

Fang, Margaret C; Chang, Yuchiao; Hylek, Elaine M; Rosand, Jonathan; Greenberg, Steven M; Go, Alan S; Singer, Daniel E

2004-11-16

The risk for atrial fibrillation-associated stroke increases at low anticoagulation intensities. However, higher intensities increase hemorrhage risk. Optimal use of warfarin for atrial fibrillation requires precise information on the risk for intracranial hemorrhage as a function of patient age and anticoagulation intensity. To examine the relationship of age, anticoagulation intensity, and risk for intracranial hemorrhage. Case-control study. Academic medical center. 170 case-patients who developed intracranial hemorrhage during warfarin therapy and 1020 matched controls who did not; both case-patients and controls were taking warfarin for atrial fibrillation. The authors performed multivariable conditional logistic regression to determine the odds of intracranial hemorrhage with regard to age and international normalized ratio (INR), controlling for comorbid conditions and aspirin use. Case-patients were older than controls (median age, 78 years vs. 75 years; P < 0.001) and had higher median INRs (2.7 vs. 2.3; P < 0.001). The risk for intracranial hemorrhage increased at 85 years of age or older (adjusted odds ratio, 2.5 [95% CI, 1.3 to 4.7]; referent age, 70 to 74 years) and at an INR range of 3.5 to 3.9 (adjusted odds ratio, 4.6 [CI, 2.3 to 9.4]; referent INR, 2.0 to 3.0). The risk for intracranial hemorrhage at INRs less than 2.0 did not differ statistically from the risk at INRs of 2.0 to 3.0 (adjusted odds ratio, 1.3 [CI, 0.8 to 2.2]). Although duration of anticoagulation has been associated with hemorrhage in other studies, the current study could not control for this potential confounder. The risk for intracranial hemorrhage increases at age 85 years. International normalized ratios less than 2.0 were not associated with lower risk for intracranial hemorrhage compared with INRs between 2.0 and 3.0. Therefore, anticoagulation management should focus on maintaining INRs in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than targeting INRs less than 2.0. Similarly, INRs of 3.5 or greater should be avoided.

Battle of oral anticoagulants in the field of atrial fibrillation scrutinized from a clinical practice (the real world) perspective

PubMed Central

2011-01-01

Warfarin has a long history of benefit and has become the gold standard medication for the prevention of ischemic stroke in patients with atrial fibrillation. Nevertheless, it is far from perfect and there is no doubt that new drugs must be found to replace warfarin. The new oral anticoagulants that are on the market or awaiting approval or under research offer some benefits but not enough to replace warfarin until results of additional studies can show an adequate balance between effectiveness/safety and cost/benefit. There are several issues concerning the new oral anticoagulants. It is essential that the effect of any anticoagulant can be measured in plasma. But to date, there is no test to assess the effect or therapeutic range for the new oral anticoagulants. There is no antidote to neutralize the action of the new drugs in cases of bleeding or when acute surgical intervention is necessary. Dabigatran requires dose adjustment in patients with moderate renal impairment and is contraindicated in patients with severe renal failure. Rivaroxaban should be used with caution in patients with severe renal impairment. Apixaban excretion is also partly dependent on renal function, although the impact of renal insufficiency has not yet been determined. How anticoagulant bridging can be done before surgery has not yet been established. In conclusion, although thousands of patients have been treated in phase III studies, additional data are necessary before conclusions can be drawn on the potential for these new anticoagulant drugs to replace warfarin in patients with atrial fibrillation. PMID:21794130

Anticoagulation for nonvalvular atrial fibrillation: effects of type of practice on physicians' self-reported behavior.

PubMed

Bush, D; Tayback, M

1998-02-01

This study examines whether social and economic factors affect physician practice and attitude with regard to warfarin anticoagulation in patients with nonvalvular atrial fibrillation. We identified physicians in Baltimore City, Baltimore County, and Prince George's County who (1) had written one or more prescriptions for a digitalis compound during the preceding year, and (2) were classified as general practitioners, family practice specialists, internists, or cardiologists. All 358 physicians fulfilling these criteria were surveyed by questionnaire. The overall response rate was 43%. Physicians who wrote 15% or more of their digitalis prescriptions for Medicaid patients said they used warfarin at significantly lower rates for patients with nonvalvular AF than other (66% versus 79%, P <0.01). The opposite pattern was seen with regard to aspirin. There were no significant differences in practice pattern between physicians located in urban vs. suburban counties. In our sample, self-reported anticoagulant practices for patients with nonvalvular AF were associated with the percentage of digitalis prescriptions written for Medicaid patients. In this metropolitan area, anticoagulant therapy was reportedly prescribed for approximately 75% of patients with nonvalvular atrial fibrillation.

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.

Pheochromocytoma diagnosed after anticoagulation for atrial fibrillation ablation procedure: a giant in disguise.

PubMed

Galvão Braga, Carlos; Ribeiro, Sílvia; Martins, Juliana; Arantes, Carina; Ramos, Vítor; Primo, João; Magalhães, Sónia; Correia, Adelino

2014-04-01

Pheochromocytoma is a rare catecholamine-producing tumor, discovered incidentally in 50% of cases. We present the case of a 44-year-old male with a history of paroxysmal palpitations. Baseline ECG, transthoracic echocardiogram and ECG stress test showed no relevant alterations. Paroxysmal atrial fibrillation was detected on 24-hour Holter ECG. After antiarrhythmic therapy, the patient remained symptomatic, and was accordingly referred for electrophysiological study and atrial fibrillation ablation. Anticoagulation was initiated before the procedure. After ablation and still anticoagulated, he complained of hematospermia. The abdominal and pelvic imaging study showed a 10-cm left adrenal mass, predominantly cystic, compatible with pheochromocytoma, which was confirmed after biochemical tests (increased urine metanephrines and plasma catecholamines). Metaiodobenzylguanidine scintigraphy scanning confirmed localized disease in the adrenal gland, excluding other uptake foci. Following appropriate preoperative management, surgical resection of the giant mass was performed successfully and without complications. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Anticoagulant and Antiplatelet Prescribing Patterns for Patients with Atrial Fibrillation after Percutaneous Coronary Intervention.

PubMed

Woods, Erin A; Ackman, Margaret L; Graham, Michelle M; Koshman, Sheri L; Boswell, Rosaleen M; Barry, Arden R

2016-01-01

Current guidelines recommend triple antithrombotic therapy (TAT), defined as acetylsalicylic acid (ASA), clopidogrel, and warfarin, for patients with nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation. The choice of anticoagulant/antiplatelet therapy in this population is ambiguous and complex, and prescribing patterns are not well documented. To characterize local prescribing patterns for anticoagulant/antiplatelet therapy after percutaneous coronary intervention in patients with nonvalvular atrial fibrillation. A chart review was conducted at a single quaternary cardiology centre. Patients with nonvalvular atrial fibrillation were identified via medical records, and those who underwent percutaneous coronary intervention were identified using a local clinical patient registry. Adult inpatients with nonvalvular atrial fibrillation and a CHADS2 score (based on congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) of 1 or higher who underwent percutaneous coronary intervention from 2011 to 2013 were included. Patients undergoing cardiovascular surgery or transcatheter aortic valve replacement, those with mechanical devices requiring anticoagulation, and those with an allergy to any component of TAT were excluded. Seventy patients were included. The median age was 75 years, and 52 (74%) were men. At discharge, 30 (43%) were receiving TAT and 27 (39%) were receiving dual antiplatelet therapy (clopidogrel and ASA). No patients received the combination of warfarin and clopidogrel. Among those who received TAT, 90% (19 of 21) who received a bare metal stent had a recommended duration of 1 month, and 75% (6 of 8) who received a drug-eluting stent had a recommended duration of 1 year. Direct-acting oral anticoagulants with 2 antiplatelet drugs were prescribed for 9% (6 of 70) of the patients, and 10% (7 of 70) received ticagrelor and ASA with or without warfarin. Overall, the combination of ASA, oral anticoagulant, and P2Y12 inhibitor was used for 54% (38/70) of the patients. Fewer than half of the patients in this study received TAT, and almost 20% received non-evidence-based therapy with a direct-acting oral anticoagulant or ticagrelor, alone or in combination. Despite current guideline recommendations, the rate of TAT utilization was lower than rates reported in the literature.

Efficacy of anticoagulation in resolving left atrial and left atrial appendage thrombi: A transesophageal echocardiographic study

NASA Technical Reports Server (NTRS)

Jaber, W. A.; Prior, D. L.; Thamilarasan, M.; Grimm, R. A.; Thomas, J. D.; Klein, A. L.; Asher, C. R.

2000-01-01

BACKGROUND: Transesophageal echocardiography (TEE) is the gold standard for evaluation of the left atrium and the left atrial appendage (LAA) for the presence of thrombi. Anticoagulation is conventionally used for patients with atrial fibrillation to prevent embolization of atrial thrombi. The mechanism of benefit and effectiveness of thrombi resolution with anticoagulation is not well defined. METHODS AND RESULTS: We used a TEE database of 9058 consecutive studies performed between January 1996 and November 1998 to identify all patients with thrombi reported in the left atrium and/or LAA. One hundred seventy-four patients with thrombi in the left atrial cavity (LAC) and LAA were identified (1.9% of transesophageal studies performed). The incidence of LAA thrombi was 6.6 times higher than LAC thrombi (151 vs 23, respectively). Almost all LAC thrombi were visualized on transthoracic echocardiography (90.5%). Mitral valve pathology was associated with LAC location of thrombi (P <.0001), whereas atrial fibrillation or flutter was present in most patients with LAA location of thrombi. Anticoagulation of 47 +/- 18 days was associated with thrombus resolution in 80.1% of the patients on follow-up TEE. Further anticoagulation resulted in limited additional benefit. CONCLUSIONS: LAC thrombi are rare and are usually associated with mitral valve pathology. Transthoracic echocardiography is effective in identifying these thrombi. LAA thrombi occur predominantly in patients with atrial fibrillation or flutter. Short-term anticoagulation achieves a high rate of resolution of LAA and LAC thrombi but does not obviate the need for follow-up TEE.

Prescription frequency and predictors for the use of novel direct oral anticoagulants for secondary stroke prevention in the first year after their marketing in Europe--a multicentric evaluation.

PubMed

Luger, Sebastian; Hohmann, Carina; Kraft, Peter; Halmer, Ramona; Gunreben, Ignaz; Neumann-Haefelin, Tobias; Kleinschnitz, Christoph; Walter, Silke; Haripyan, Veronika; Steinmetz, Helmuth; Foerch, Christian; Pfeilschifter, Waltraud

2014-07-01

Direct oral anticoagulants (DOAC) are alternatives to the use of vitamin K antagonists (VKA) as oral anticoagulant therapies to prevent stroke in patients with atrial fibrillation. We assembled a representative secondary prevention cohort from four tertiary care stroke centers to identify factors that independently influence therapeutic decision making 1) not to anticoagulate with either VKA or DOAC and 2) to use DOAC if the patient appears suitable for oral anticoagulant therapy. We identified all patients discharged with the diagnoses 'ischemic stroke' (ICD-10 code I63) or 'transient ischemic attack' (G45) in combination with 'atrial fibrillation' (I48) during 1 year. We performed binary logistic regression analyses to identify factors independently influencing the aforementioned decisions. Our cohort comprised 758 patients. At discharge from the stroke service, 374 patients (49·3%) received oral anticoagulant therapy. Older age, severe stroke, poor recovery in the acute phase, and higher serum creatinine were independent factors to withhold oral anticoagulant therapy, whereas prior oral anticoagulant therapy favored the decision to anticoagulate. Among patients who were anticoagulated, prescription was balanced for VKA (50·3%) and DOAC (49·7%). Renal function and prior oral anticoagulant therapies were the most important factors in this decision. Shortly after their marketing, DOAC are used as frequently as VKA for secondary stroke prevention in patients with atrial fibrillation. The decision between VKA and DOAC is mainly determined by the patient's renal function and the absence or presence of prior oral anticoagulant therapy. © 2014 World Stroke Organization.

Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: The SAMURAI‐NVAF Study

PubMed Central

Arihiro, Shoji; Todo, Kenichi; Yamagami, Hiroshi; Kimura, Kazumi; Furui, Eisuke; Terasaki, Tadashi; Shiokawa, Yoshiaki; Kamiyama, Kenji; Takizawa, Shunya; Okuda, Satoshi; Okada, Yasushi; Kameda, Tomoaki; Nagakane, Yoshinari; Hasegawa, Yasuhiro; Mochizuki, Hiroshi; Ito, Yasuhiro; Nakashima, Takahiro; Takamatsu, Kazuhiro; Nishiyama, Kazutoshi; Kario, Kazuomi; Sato, Shoichiro; Koga, Masatoshi; Nagatsuka, K; Minematsu, K; Nakagawara, J; Akiyama, H; Shibazaki, K; Maeda, K; Shibuya, S; Yoshimura, S; Endo, K; Miyagi, T; Osaki, M; Kobayashi, J; Okata, T; Tanaka, E; Sakamoto, Y; Takizawa, H; Takasugi, J; Tokunaga, K; Homma, K; Kinoshita, N; Matsuki, T; Higashida, K; Shiozawa, M; Kanai, H; Uehara, S

2015-01-01

Background Large clinical trials are lack of data on non‐vitamin K antagonist oral anticoagulants for acute stroke patients. Aim To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk‐factor Assessment and Improvement‐NVAF registry (ClinicalTrials.gov NCT01581502). Method The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23‐day stay) was assessed. Results Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10‐month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS 2, CHA 2 DS 2‐VASc, and HAS‐BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four‐days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20‐day or shorter hospitalization (OR 2·46, 95% CI 1·87–3·24). Conclusions Warfarin use at acute hospital discharge was still common in the initial years after approval of nonvitamin K antagonist oral anticoagulants, although nonvitamin K antagonist oral anticoagulant users increased gradually. The index stroke was milder and ischemia‐risk indices were lower in nonvitamin K antagonist oral anticoagulant users than in warfarin users. Early initiation of nonvitamin K antagonist oral anticoagulants seemed safe. PMID:25581108

Real-World Use of Apixaban for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Meta-Analysis.

PubMed

Proietti, Marco; Romanazzi, Imma; Romiti, Giulio Francesco; Farcomeni, Alessio; Lip, Gregory Y H

2018-01-01

The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of nonvitamin K antagonist oral anticoagulants would help elucidate their effectiveness and safety in daily clinical practice. Apixaban was the third nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and increasing real-world studies have been published. Our aim was to summarize current evidence about real-world studies on apixaban for stroke prevention in atrial fibrillation. We performed a systematic review and meta-analysis of all observational real-world studies comparing apixaban with other available oral anticoagulant drugs. From the original 9680 results retrieved, 16 studies have been included in the final meta-analysis. Compared with warfarin, apixaban regular dose was more effective in reducing any thromboembolic event (odds ratio: 0.77; 95% confidence interval: 0.64-0.93), but no significant difference was found for stroke risk. Apixaban was as effective as dabigatran and rivaroxaban in reducing thromboembolic events and stroke. The risk of major bleeding was significantly lower for apixaban compared with warfarin, dabigatran, and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively). Similarly, the risk for intracranial hemorrhage was significantly lower for apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when compared with all oral anticoagulant agents ( P <0.00001 for all comparisons). Use of apixaban in real-life is associated with an overall similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin. A better safety profile was found with apixaban compared with warfarin, dabigatran, and rivaroxaban. © 2017 American Heart Association, Inc.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

2015-08-01

The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants. © 2015 American Heart Association, Inc.

The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands.

PubMed

Ten Cate, V; Ten Cate, H; Verheugt, F W A

2016-10-01

There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients.

Predicting Major Bleeding in Ischemic Stroke Patients With Atrial Fibrillation.

PubMed

Hilkens, Nina A; Algra, Ale; Greving, Jacoba P

2017-11-01

Performance of risk scores for major bleeding in patients with atrial fibrillation and a previous transient ischemic attack or ischemic stroke is not well established. We aimed to validate risk scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulants after cerebral ischemia and explore the net benefit of oral anticoagulants among bleeding risk categories. We analyzed 3623 patients with a history of transient ischemic attack or stroke included in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). We assessed performance of HEMORR 2 HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age, reduced platelet count or function, hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), Shireman, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and ORBIT scores (older age, reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) with C statistics and calibration plots. Net benefit of oral anticoagulants was explored by comparing risk reduction in ischemic stroke with risk increase in major bleedings on warfarin. During 6922 person-years of follow-up, 266 patients experienced a major bleed (3.8 per 100 person-years). C statistics ranged from 0.62 (Shireman) to 0.67 (ATRIA). Calibration was poor for ATRIA and moderate for other models. The reduction in recurrent ischemic strokes on warfarin was larger than the increase in major bleeding risk, irrespective of bleeding risk category. Performance of prediction models for major bleeding in patients with cerebral ischemia and atrial fibrillation is modest but comparable with performance in patients with only atrial fibrillation. Bleeding risk scores cannot guide treatment decisions for oral anticoagulants but may still be useful to identify modifiable risk factors for bleeding. Clinical usefulness may be best for ORBIT, which is based on a limited number of easily obtainable variables and showed reasonable performance. © 2017 American Heart Association, Inc.

Rivaroxaban as an effective alternative to warfarin in a patient with atrial fibrillation, thrombophilia, and left atrial appendage thrombus: a case report.

PubMed

Scarano, Michele; Casale, Matteo; Mantini, Cesare; Imbalzano, Egidio; Consorti, Cristiana; Clemente, Daniela; Dattilo, Giuseppe

2017-04-09

Atrial fibrillation is the most common cardiac arrhythmia. It is responsible for up to 20% of all ischemic strokes. Rate control and anticoagulation are crucial for atrial fibrillation management and stroke prevention. We present the case of an 84-year-old Italian woman with a left atrial appendage thrombus that developed despite her use of anticoagulant therapy with warfarin for a previous pulmonary embolism. She had atrial fibrillation and heterozygosity for both factor V Leiden and methylenetetrahydrofolate reductase C677T mutation, thus creating resistance to activated protein C. Anticoagulant therapy was switched to heparin for 1 week and then to rivaroxaban. After 3 months of rivaroxaban use, the thrombus disappeared. This case raises the issue of the ineffectiveness of warfarin therapy in complex cases involving particular thrombophilic conditions and the possibility of using rivaroxaban as a safe and effective alternative.

Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

PubMed

Minhas, Anum S; Jiang, Qingmei; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2016-11-01

All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance <50 mL/min and 23 (12.2 %) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

Cost Effectiveness of Implantable Cardiac Monitor-Guided Intermittent Anticoagulation for Atrial Fibrillation: An Analysis of the REACT.COM Pilot Study.

PubMed

Steinhaus, Daniel A; Zimetbaum, Peter J; Passman, Rod S; Leong-Sit, Peter; Reynolds, Matthew R

2016-08-30

Anticoagulation guidelines for patients with atrial fibrillation (AF) disregard AF burden. A strategy of targeted anticoagulation with novel oral anticoagulants (NOACs) based on continuous rhythm assessment with an implantable cardiac monitor (ICM) has recently been explored. We evaluated the potential cost-effectiveness of this strategy versus projected outcomes with continuous anticoagulation. We developed a Markov model using data from the Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT.COM) pilot study (N = 59) and prior NOAC trials to calculate the costs and quality-adjusted life years (QALYs) associated with ICM-guided intermittent anticoagulation for AF versus standard care during a 3-year time horizon. Health state utilities were estimated from the pilot study population using the SF-12. Costs were based on current Medicare reimbursement. Over 14 ± 4 months of follow-up, 18 of 59 patients had 35 AF episodes. The ICM-guided strategy resulted in a 94% reduction in anticoagulant use relative to continuous treatment. There were no strokes, 3 (5.1%) TIAs, 2 major bleeding events (on aspirin) and 3 minor bleeding events with the ICM-guided strategy. The projected total 3-year costs were $12,535 for the ICM-guided strategy versus $13,340 for continuous anticoagulation. Projected QALYs were 2.45 for both groups. Based on a pilot study, a strategy of ICM-guided anticoagulation with NOACs may be cost-saving relative to expected outcomes with continuous anticoagulation, with similar quality-adjusted survival. This strategy could be attractive from a health economic perspective if shown to be safe and effective in a rigorous clinical trial. © 2016 Wiley Periodicals, Inc.

Cost Effectiveness of Implantable Cardiac Monitor-Guided Intermittent Anticoagulation for Atrial Fibrillation: An Analysis of the REACT.COM Pilot Study

PubMed Central

Steinhaus, Daniel A; Zimetbaum, Peter J; Passman, Rod S; Leong-Sit, Peter; Reynolds, Matthew R.

2016-01-01

Introduction Anticoagulation guidelines for patients with atrial fibrillation (AF) disregard AF burden. A strategy of targeted anticoagulation with novel oral anticoagulants (NOACs) based on continuous rhythm assessment with an implantable cardiac monitor (ICM) has recently been explored. We evaluated the potential cost-effectiveness of this strategy versus projected outcomes with continuous anticoagulation. Methods and Results We developed a Markov model using data from the Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT.COM) pilot study (N=59) and prior NOAC trials to calculate the costs and quality-adjusted life years (QALYs) associated with ICM-guided intermittent anticoagulation for AF vs. standard care over a 3-year time horizon. Health state utilities were estimated from the pilot study population using the SF-12. Costs were based on current Medicare reimbursement. Over 14±4 months of follow-up 18 of 59 patients had 35 AF episodes. The ICM-guided strategy resulted in a 94% reduction in anticoagulant use relative to continuous treatment. There were no strokes, 3 (5.1%) TIAs, 2 major bleeding events (on aspirin) and 3 minor bleeding events with the ICM-guided strategy. The projected total 3-year costs were $12,535 for the ICM-guided strategy vs. $13,340 for continuous anticoagulation. Projected QALYs were 2.45 for both groups. Conclusion Based on a pilot study, a strategy of ICM-guided anticoagulation with NOACs may be cost-saving relative to expected outcomes with continuous anticoagulation, with similar quality-adjusted survival. This strategy could be attractive from a health economic perspective if shown to be safe and effective in a rigorous clinical trial. PMID:27571718

Risk of stroke and oral anticoagulant use in atrial fibrillation: a cross-sectional survey

PubMed Central

Holt, Tim A; Hunter, Tina D; Gunnarsson, Candace; Khan, Nada; Cload, Paul; Lip, Gregory YH

2012-01-01

Background Oral anticoagulants substantially reduce the risk of stroke in atrial fibrillation but are underutilised in current practice. Aim To measure the distribution of stroke risk in patients with atrial fibrillation (using the CHADS2 and CHA2DS2-VASc scores) and changes in oral anticoagulant use during 2007–2010. Design and setting Longitudinal series of cross-sectional survey in 583 UK practices linked to the QResearch® database providing 99 351 anonymised electronic records from people with atrial fibrillation. Method The proportion of patients in each CHADS2 and CHA2DS2-VASc risk band in 2010 was calculated; for each of the years 2007–2010, the proportions with risk scores ≥2 that were using anticoagulants or antiplatelet agents were estimated. The proportions identified at high risk were re-estimated using alternative definitions of hypertension based on coded data. Finally, the prevalence of comorbid conditions in treated and untreated high-risk (CHADS2 ≥2) groups was derived. Results The proportion at high risk of stroke in 2010 was 56.9% according to the CHADS2 ≥2 threshold, and 84.5% according to CHA2DS2-VASc ≥2 threshold. The proportions of these groups receiving anticoagulants were 53.0% and 50.7% respectively and increased during 2007–2010. The means of identifying the population of individuals with hypertension significantly influenced the estimated proportion at high risk. Comorbid conditions associated with avoidance of anticoagulants included history of falls, use of nonsteroidal anti-inflammatory drugs, and dementia. Conclusion Oral anticoagulant use in atrial fibrillation has increased in UK practice since 2007, but remains suboptimal. Improved coding of hypertension is required to support systematic identification of individuals at high risk of stroke and could be assisted by practice-based software. PMID:23265231

[Prophylaxis of thromboembolism in atrial fibrillation: new oral anticoagulants and left atrial appendage closure].

PubMed

Zeus, Tobias; Kelm, Malte; Bode, Christoph

2015-08-01

Thrombo-embolic prophylaxis is a key element within the therapy of atrial fibrillation/atrial flutter. Besides new oral anticoagulants the concept of left atrial appendage occlusion has approved to be a good alternative option, especially in patients with increased risk of bleeding. © Georg Thieme Verlag KG Stuttgart · New York.

The prevalence of oral anticoagulation in patients with atrial fibrillation in Portugal: Systematic review and meta-analysis of observational studies.

PubMed

Caldeira, Daniel; Barra, Márcio; David, Cláudio; Costa, João; Ferreira, Joaquim J; Pinto, Fausto J

2014-09-01

Oral anticoagulation (OAC) is an effective treatment in the prevention of thromboembolic events in patients with atrial fibrillation (AF). The aim of this review was to estimate the prevalence of OAC therapy in patients with AF in Portugal. MEDLINE, the Index of Portuguese Medical Journals and SIBUL (the Bibliographic Catalog of the Integrated Library System of the University of Lisbon) were searched for Portuguese observational studies reporting the proportion of anticoagulated patients with AF. The pooled estimated prevalence of anticoagulated patients and respective 95% confidence interval (CI) were determined by means of a meta-analysis. Seven studies were included for analysis, of which four were conducted in a hospital environment and three in the general community. These studies enrolled a total of 891 patients with AF. The pooled estimated prevalence of anticoagulated patients was 40% (95% CI: 32-48%). The prevalence of OAC in Portuguese AF patients is low. There is a need to promote change in OAC prescribing habits for AF patients in Portugal, in accordance with international guidelines. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Atrial Fibrillation, Type 2 Diabetes, and Non-Vitamin K Antagonist Oral Anticoagulants: A Review.

PubMed

Plitt, Anna; McGuire, Darren K; Giugliano, Robert P

2017-04-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a 5-fold increase in the risk for stroke. Type 2 diabetes is an independent risk factor for both stroke and atrial fibrillation, and in the setting of AF, type 2 diabetes is independently associated with a 2% to 3.5% increase in absolute stroke rate per year. The overlap in the pathophysiologies of AF and type 2 diabetes are not well understood, and current practice guidelines provide few recommendations regarding patients with both conditions. In this article, we review the epidemiology and pathophysiology of the nexus of AF and type 2 diabetes. Furthermore, we analyze the subgroup of patients with type 2 diabetes enrolled in phase 3 clinical trials of non-vitamin K antagonist oral anticoagulants in prevention of arterial thromboembolism in AF, highlighting the greater absolute benefit of non-vitamin K oral anticoagulants in patients with type 2 diabetes. Finally, we offer recommendations on risk stratification and therapy for patients with concomitant AF and type 2 diabetes. We highlight the increased thromboembolic risk with coexisting AF and type 2 diabetes. We recommend that further studies be done to evaluate the potential benefits of anticoagulation for all patients who have both and the potential for non-vitamin K oral anticoagulants to have greater benefits than risks over vitamin K antagonists.

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.

Healthcare resources and needs in anticoagulant therapy for patients with nonvalvular atrial fibrillation. SAMOA Study.

PubMed

Barrios, V; Egocheaga-Cabello, M I; Gállego-Culleré, J; Ignacio-García, E; Manzano-Espinosa, L; Martín-Martínez, A; Mateo-Arranz, J; Polo-García, J; Vargas-Ortega, D

2017-05-01

To determine, in the various medical specialties, the healthcare process for anticoagulated patients with nonvalvular atrial fibrillation, to determine the available and necessary resources and to identify potential areas of improvement in the care of these patients. We performed a cross-sectional survey of primary care and specialised physicians involved in the care of anticoagulated patients. The questionnaires referred to the healthcare process, the indication and prescription of anticoagulant therapy and the barriers and deficiencies present for these patients. A total of 893 physicians participated in the study, 437 of whom worked in primary care and 456 of whom were specialists (mostly cardiologists). Forty-two percent of the family doctors indicated that they assessed and prescribed anticoagulant therapy, and 66% performed the regular follow-up of these patients. In both healthcare settings, the physicians noted the lack of standardised protocols. There was also a lack of quality control in the treatment. The role of primary care in managing anticoagulated patients has grown compared with previous reports. The responses of the participating physicians suggest marked gaps in the standardisation of the healthcare process and several areas for improvement in these patients' follow-up. The promotion of training in direct-acting anticoagulant drugs remains pivotal. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Risk scores and geriatric profile: can they really help us in anticoagulation decision making among older patients suffering from atrial fibrillation?

PubMed

Maes, Frédéric; Dalleur, Olivia; Henrard, Séverine; Wouters, Dominique; Scavée, Christophe; Spinewine, Anne; Boland, Benoit

2014-01-01

Anticoagulation for the prevention of cardio-embolism is most frequently indicated but largely underused in frail older patients with atrial fibrillation (AF). This study aimed at identifying characteristics associated with anticoagulation underuse. A cross-sectional study of consecutive geriatric patients aged ≥75 years, with AF and clear anticoagulation indication (CHADS₂ [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack] ≥2) upon hospital admission. All patients benefited from a comprehensive geriatric assessment. Their risks of stroke and bleeding were predicted using CHADS₂ and HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age >75 years), Reduced platelet count or function, Rebleed risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, and Stroke) scores, respectively. Anticoagulation underuse was observed in 384 (50%) of 773 geriatric patients with AF (median age 85 years; female 57%, cognitive disorder 33%, nursing home 20%). No geriatric characteristic was found to be associated with anticoagulation underuse. Conversely, anticoagulation underuse was markedly increased in the patients treated with aspirin (odds ratio [OR] [95% confidence interval]: 5.3 [3.8; 7.5]). Other independent predictors of anticoagulation underuse were ethanol abuse (OR: 4.0 [1.4; 13.3]) and age ≥90 years (OR: 2.0 [1.2; 3.4]). Anticoagulation underuse was not inferior in patients with a lower bleeding risk and/or a higher stroke risk and underuse was surprisingly not inferior either in the AF patients who had previously had a stroke. Half of this geriatric population did not receive any anticoagulation despite a clear indication, regardless of their individual bleeding or stroke risks. Aspirin use is the main characteristic associated with anticoagulation underuse.

Risk scores and geriatric profile: can they really help us in anticoagulation decision making among older patients suffering from atrial fibrillation?

PubMed Central

Maes, Frédéric; Dalleur, Olivia; Henrard, Séverine; Wouters, Dominique; Scavée, Christophe; Spinewine, Anne; Boland, Benoit

2014-01-01

Objectives Anticoagulation for the prevention of cardio-embolism is most frequently indicated but largely underused in frail older patients with atrial fibrillation (AF). This study aimed at identifying characteristics associated with anticoagulation underuse. Methods A cross-sectional study of consecutive geriatric patients aged ≥75 years, with AF and clear anticoagulation indication (CHADS2 [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack] ≥2) upon hospital admission. All patients benefited from a comprehensive geriatric assessment. Their risks of stroke and bleeding were predicted using CHADS2 and HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age >75 years), Reduced platelet count or function, Rebleed risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, and Stroke) scores, respectively. Results Anticoagulation underuse was observed in 384 (50%) of 773 geriatric patients with AF (median age 85 years; female 57%, cognitive disorder 33%, nursing home 20%). No geriatric characteristic was found to be associated with anticoagulation underuse. Conversely, anticoagulation underuse was markedly increased in the patients treated with aspirin (odds ratio [OR] [95% confidence interval]: 5.3 [3.8; 7.5]). Other independent predictors of anticoagulation underuse were ethanol abuse (OR: 4.0 [1.4; 13.3]) and age ≥90 years (OR: 2.0 [1.2; 3.4]). Anticoagulation underuse was not inferior in patients with a lower bleeding risk and/or a higher stroke risk and underuse was surprisingly not inferior either in the AF patients who had previously had a stroke. Conclusion Half of this geriatric population did not receive any anticoagulation despite a clear indication, regardless of their individual bleeding or stroke risks. Aspirin use is the main characteristic associated with anticoagulation underuse. PMID:25053883

Stroke prophylaxis with warfarin or dabigatran for patients with non-valvular atrial fibrillation-cost analysis.

PubMed

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-09-01

cost of anticoagulation with dabigatran is largely based on estimation of complication rates derived from clinical trials. to investigate cost of anticoagulation with dabigatran in comparison with warfarin in clinical practice. a prospective observational study of patients with non-vavular atrial fibrillation (NVAF) referred to anticoagulation clinic. Patients were interviewed (4-6 weekly by telephone) about bleeding events. Costs of anticoagulation were calculated as: (i) drug cost, (ii) international normalised ratio (INR) monitoring cost and (iii) bleeding cost. For cost calculation of dabigatran, INR monitoring cost was omitted. a total of 402 patients were included and followed up for a mean (SD) of 19 (8.1) months. Annual cost of anticoagulation was £207.3 and £1,573.5 per patient for warfarin and dabigatran, respectively. Drug price constituted 13.6% of the total cost for warfarin and 94% for dabigatran. Total cost of anticoagulation to prevent one stroke per year was £6,219, £28,086.5 and £25,181 for warfarin, dabigatran 110 and 150 mg, respectively. cost of anticoagulation is mainly driven by drug price for dabigatran and quality of INR control for warfarin. Until the price of dabigatran is reviewed, warfarin remains suitable for the majority of patients with NVAF.

Meta-analysis of CHADS2 versus CHA2DS2-VASc for predicting stroke and thromboembolism in atrial fibrillation patients independent of anticoagulation.

PubMed

Zhu, Wen-Gen; Xiong, Qin-Mei; Hong, Kui

2015-02-01

Two validated scoring systems for predicting embolic risk, CHADS2 and CHA2DS2-VASc, contribute to optimizing antithrombotic prescription practices in patients who have atrial fibrillation. However, data about anticoagulated patients are sparse. We compared CHADS2 and CHA2DS2-VASc, in terms of their predictive risk evaluation, in patients with atrial fibrillation who were and were not taking anticoagulants. We systematically searched the Cochrane Library, PubMed, and Embase databases for studies of the comparative diagnostic performance of CHADS2 and CHA2DS2-VASc. We identified 12 cohort studies for meta-analysis. With regard to the occurrence of cardiovascular events individually, patients with CHA2DS2-VASc scores ≥2 have a greater risk of stroke (risk ratio [RR]=5.15; 95% confidence interval [CI], 3.85-6.88; P <0.00001) and thromboembolism (RR=5.96; 95% CI, 5.50-6.45; P <0.00001) (P diff=0.34) than do patients with CHA2DS2-VASc scores <2, independent of anticoagulation therapy (RR=5.76; 95% CI, 5.23-6.35; P <0.00001 in anticoagulated patients; and RR=6.12; 95% CI, 5.40-6.93; P <0.00001 in patients not taking anticoagulants; P diff=0.45). The pooled RR estimates indicate an approximate 6-fold increase in the risk of endpoint events in patients with CHA2DS2-VASc scores ≥2 (RR=5.90; 95% CI, 5.46-6.37; P <0.0001). These results clearly indicate the discriminative capacity of the CHA2DS2-VASc score for stroke, thromboembolic events, or both, independent of optimal anticoagulation. The CHA2DS2-VASc score enables the identification of patients who are at genuinely high risk and can direct the selection of appropriate therapeutic approaches.

Novel oral anticoagulants for atrial fibrillation.

PubMed

How, Choon How

2015-12-01

Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes.

Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

PubMed

Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Gorst-Rasmussen, Anders; Rasmussen, Lars Hvilsted; Lip, Gregory Y H

2015-08-11

Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively. Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality rates, supporting oral anticoagulant treatment reintroduction after intracranial hemorrhage as feasible. Future trials are encouraged to guide clinical practice in these patients. © 2015 American Heart Association, Inc.

[Splenic infarction after warfarin discontinuation during atrial fibrillation].

PubMed

Trappolini, M; Scorzai, A; Loguercio, V; Stoppo, M; Sebastianelli, A; Iannotta, M; Del Porto, F; Proietta, M; Aliberti, G

2008-01-01

We describe a case of patient with splenic infarction, admitted to our department for sudden abdominal pain and fever after discontinuation of anticoagulant therapy for atrial fibrillation, complicating a dilated myocardiopathy and mechanical prosthetic valve. Diagnosis of splenic infarction was made by enhanced-contrast computed tomography, while ultrasounds and radiography were negative. Anticoagulant therapy, gold-standard treatment, was followed by fast clinical improvement. Moreover, splenic infarction should be considered in all cases of acute or chronic pain in left hypochondrium and especially in patients with emboligenous cardiopathies or atrial fibrillation, the most common arrhythmia source of peripheral embolism in clinical practice.

Understanding and Managing Atrial Fibrillation in Patients with Kidney Disease.

PubMed

Khouri, Yazan; Stephens, Tiona; Ayuba, Gloria; AlAmeri, Hazim; Juratli, Nour; McCullough, Peter A

2015-01-01

Chronic kidney disease (CKD) is on the rise due to the increased rate of related comorbidities such as diabetes and hypertension. Patients with CKD are at higher risk of cardiovascular events and atrial fibrillation is more common in this patient population. It is estimated that the prevalence of chronic atrial fibrillation in patients with CKD is two to three times higher than general population. Furthermore, patients with CKD are less likely to stay in sinus rhythm. Atrial fibrillation presents a major burden in this population due to difficult treatment decisions in the setting of a lack of evidence from randomized clinical trials. Patients with CKD have higher risk of stroke with more than half having a CHADS2 score ≥ 2. Anticoagulation have been shown to significantly decrease embolic stroke risk, however bleeding complications such as hemorrhagic stroke is twofold higher with warfarin. Although newer novel anticoagulation drugs have shown promise with lower intracranial hemorrhage risk in comparison to warfarin, lack clinical trial data in CKD and the unavailability of an antidote remains an issue. In this review, we discuss the treatment options available including anticoagulation and the evidence behind them in patients with chronic kidney disease suffering from atrial fibrillation.

Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial Fibrillation in Older People: Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016).

PubMed

Wehling, Martin; Collins, Ronan; Gil, Victor M; Hanon, Olivier; Hardt, Roland; Hoffmeister, Martin; Monteiro, Pedro; Quinn, Terence J; Ropers, Dieter; Sergi, Giuseppe; Verheugt, Freek W A

2017-07-01

Age appropriateness of anticoagulants for stroke prevention in atrial fibrillation is uncertain. To review oral anticoagulants for the treatment of atrial fibrillation in older (age >65 years) people and to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability using the Fit-fOR-The-Aged (FORTA) classification. We performed a structured comprehensive review of controlled clinical trials and summaries of individual product characteristics to assess study and total patient numbers, quality of major outcome data and data of geriatric relevance. The resulting evidence was discussed in a round table with an interdisciplinary panel of ten European experts. Decisions on age appropriateness were made using a Delphi process. For the eight drugs included, 380 citations were identified. The primary outcome results were reported in 32 clinical trials with explicit and relevant data on older people. Though over 24,000 patients aged >75/80 years were studied for warfarin, data on geriatric syndromes were rare (two studies reporting on frailty/falls/mental status) and missing for all other compounds. Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist oral anticoagulants (including low/high-intensity dabigatran and high-intensity edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon, acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting the absence of data. All non-vitamin K antagonist oral anticoagulants and warfarin were classified as beneficial or very beneficial in older persons (FORTA-A or -B), underlining the overall positive assessment of the risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally used in Europe, the lack of evidence should challenge current practice.

Underuse of Anticoagulation in Older Patients with Atrial Fibrillation and CHADS2 Score ≥ 2: Are We Doing Better Since the Marketing of Direct Oral Anticoagulants?

PubMed

Henrard, Séverine; Vandenabeele, Caroline; Marien, Sophie; Boland, Benoit; Dalleur, Olivia

2017-11-01

Our objectives were to (1) describe the evolution of the underuse of anticoagulants in older people with atrial fibrillation (AF) and a CHADS 2 score ≥ 2 since direct oral anticoagulants (DOACs) were introduced to the market and (2) describe factors associated with this underuse. We conducted a retrospective cross-sectional study including geriatric patients admitted during the pre-DOAC (2008-2011) and post-DOAC (2013-2015) periods in an academic hospital in Belgium. Five inclusion criteria were met: age ≥ 75 years, diagnosis of AF, indication for anticoagulation (CHADS 2 score ≥ 2), risk of functional decline (Identification of Seniors At Risk [ISAR] score ≥ 2), and comprehensive geriatric assessment. The use of anticoagulants and antiplatelets at home before admission was recorded. Risks of stroke and bleeding were calculated using CHADS 2 and HEMORR 2 HAGES scores, respectively. Three different logistic regression models were performed to describe the evolution of and factors associated with the underuse of anticoagulants after DOAC marketing. Anticoagulant underuse, present in 209 of 614 (34%) geriatric patients with AF, was lower in patients with a history of stroke (28.5%) or congestive heart failure (26.9%) but higher in those receiving antiplatelets (56.2%) and in older individuals. Anticoagulant underuse decreased significantly from the pre-DOAC (37.3%) to the post-DOAC (29.7%) era, as shown by two analyses using propensity scores. In older patients with AF, anticoagulant underuse was mainly associated with antiplatelet use. Anticoagulant underuse and antiplatelet use have both decreased since DOAC marketing. Underuse of anticoagulants was still a concern for three in ten geriatric patients with AF at high risk of stroke (CHADS 2 score ≥ 2).

Stroke prophylaxis in atrial fibrillation: searching for management improvement opportunities in the emergency department: the HERMES-AF study.

PubMed

Coll-Vinent, Blanca; Martín, Alfonso; Malagón, Francisco; Suero, Coral; Sánchez, Juan; Varona, Mercedes; Cancio, Manuel; Sánchez, Susana; Montull, Eugeni; Del Arco, Carmen

2015-01-01

We determine the prevalence of stroke prophylaxis prescription in emergency department (ED) patients with atrial fibrillation and the factors associated with a lack of prescription of anticoagulation in high-risk patients without contraindications. This was a multicenter, observational, cross-sectional study with prospective standardized data collection carried out in 124 Spanish EDs. Clinical variables, risk factors for stroke, type of prophylaxis prescribed, and reasons for not prescribing anticoagulation in high-risk patients (congestive heart failure/left ventricular dysfunction, hypertension, age >75 years, diabetes and previous stroke/transient ischemic attack/systemic embolism [CHADS2] score ≥2 and the congestive heart failure/left ventricular dysfunction, hypertension, age >75 years, diabetes, previous stroke/transient ischemic attack/systemic embolism, vascular disease age 65 to 74 years and sex category [CHA2DS2-VASc] score ≥2) without contraindications were collected. Of 3,276 patients enrolled, 71.5% were at high risk according to CHADS2; 89.7% according to CHA2DS2-VASc. At discharge from the ED, 2,255 patients (68.8%) were receiving anticoagulants, 1,691 of whom (75%) were high-risk patients. Of the 1,931 patients discharged home, anticoagulation was prescribed for 384 patients (19.9%) de novo and for 932 patients (48.3%) previously receiving anticoagulation. The main reasons for not prescribing anticoagulation to eligible patients were considering antiplatelet therapy as adequate prophylaxis (33.1%), advanced age (15%), and considering stroke risk as low (8.3%). Advanced age (odds ratio 0.46; 95% confidence interval 0.30 to 0.69) and female sex (odds ratio 0.50; 95% confidence interval 0.36 to 0.71) were significantly associated with the lack of prescription of anticoagulation to eligible patients. In Spain, most patients with atrial fibrillation treated in EDs who do not receive anticoagulation are at high risk of stroke, with relevant differences with regard to the risk stratification scheme used. Anticoagulation is underused, mainly because the risk of stroke is underestimated by the treating physicians and the benefits of antiplatelets are overrated, principally in female patients and the elderly. Efforts to increase the prescription of anticoagulation in these patients appear warranted. Copyright © 2014 American College of Emergency Physicians. 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.

Percutaneous Occlusion of the Left Atrial Appendage with the Watchman Device in an Active Duty Sailor with Atrial Fibrillation and Recurrent Thromboembolism Despite Appropriate Use of Oral Anticoagulation.

PubMed

Cox, Justin M; Choi, Anthony J; Oakley, Luke S; Francisco, Gregory M; Nayak, Keshav R

2018-05-23

Atrial fibrillation is the most common significant cardiac arrhythmia and is associated with a five-fold increased risk of stroke from thromboembolism. Over 94% of these emboli arise from the left atrial appendage. Systemic embolic phenomena are rare, accounting for less than 1 out of 10 of all embolic events, but have a similar prevention strategy. Anticoagulation significantly reduces the risk of these events, and thus forms the cornerstone of therapy for most patients with atrial fibrillation. Left atrial appendage occlusion with the Watchman device is a recently approved alternative for stroke prevention in selected patients. We present a case of an active duty U.S. Navy sailor at low risk for thromboembolism who nonetheless suffered recurrent thromboembolic events despite appropriate anticoagulation, and thus underwent Watchman implantation. The therapy in this case will ideally provide a lifetime of protection from recurrent systemic embolization while allowing the patient to continue his active duty military career without restriction due to oral anticoagulation.

Outcomes of Temporary Interruption of Rivaroxaban Compared With Warfarin in Patients With Nonvalvular Atrial Fibrillation

PubMed Central

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.

2014-01-01

Background 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. Methods and Results 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). Conclusions 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. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767. PMID:24552831

Novel oral anticoagulants for atrial fibrillation

PubMed Central

How, Choon How

2015-01-01

Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes. PMID:26702159

Rhythmic chaos: irregularities of computer ECG diagnosis.

PubMed

Wang, Yi-Ting Laureen; Seow, Swee-Chong; Singh, Devinder; Poh, Kian-Keong; Chai, Ping

2017-09-01

Diagnostic errors can occur when physicians rely solely on computer electrocardiogram interpretation. Cardiologists often receive referrals for computer misdiagnoses of atrial fibrillation. Patients may have been inappropriately anticoagulated for pseudo atrial fibrillation. Anticoagulation carries significant risks, and such errors may carry a high cost. Have we become overreliant on machines and technology? In this article, we illustrate three such cases and briefly discuss how we can reduce these errors. Copyright: © Singapore Medical Association.

A new therapeutic strategy for electrical cardioversion of atrial fibrillation.

PubMed

de Luca, I; Sorino, M; Del Salvatore, B; de Luca, L

2001-11-01

The conventional approach to cardioversion of atrial fibrillation includes a period of anticoagulation with oral anticoagulant therapy (OAT) extending from 3 weeks precardioversion to 4 weeks postcardioversion. The protocol of rapid anticoagulation (such as that of the ACUTE study) consists of a precardioversion transesophageal echocardiography (TEE) followed by OAT for 4 weeks. In the last few years low-molecular-weight heparins have established themselves as a safe and efficacious alternative to traditional antithrombotic therapies. The aim of this study was to demonstrate that the exclusion of thrombi by precardioversion TEE together with the exclusion of atrial stunning by a second TEE performed after 1 week, to date not suggested in the literature, could reduce to 7 days the period of pericardioversion anticoagulation. This therapy would be carried out using low-molecular-weight heparins with no need for biological monitoring and with the possibility of self-administration. We have studied 57 consecutive patients who had atrial fibrillation or flutter with a history of atrial fibrillation lasting > 48 hours. All patients received enoxaparin at a dosage of 100 IU antiXa/kg twice daily before undergoing multiplane TEE. Previous informed consent and ethical committee authorization had been obtained. Twenty-four hours following TEE, in the absence of thrombi and/or spontaneous moderate/severe echocontrast in the atrial chambers, the patients underwent electrical cardioversion and were discharged within 24 hours of sinus rhythm restoration. These patients were prescribed enoxaparin at the indicated dosage twice daily until TEE, performed in an outpatients setting 7 days following cardioversion. In the absence of thrombi and/or atrial and/or left atrial appendage stunning, OAT was terminated. Enoxaparin was associated with OAT for the following 3 weeks if any of the following signs of stunning were present: A wave inferior to the normal value for age at transmitral Doppler; a left atrial appendage emptying velocity < 40 cm/s; the appearance or increase in the severity of spontaneous echocontrast. For all patients, clinical and electrocardiographic follow-up was carried out at 1 month. In one patient TEE was not tolerated and one refused it. In 7 patients cardioversion was not performed: 4 because of the presence of thrombi, 1 because of moderate/severe spontaneous echocontrast and 2 owing to spontaneous cardioversion. Of the remaining 48 patients, cardioversion proved to be efficacious in 38, with sustained sinus rhythm at 1 week in 33 patients. One of these refused the second TEE and of the remaining 32 patients, 24 (75%) showed no signs of stunning at the second TEE and so anticoagulation was terminated. Thus, after 1 week, 75% (24/33) of patients in sinus rhythm could benefit from a shortened anticoagulation therapy which lasted for a mean of only 8.5 days. No patients showed signs of a thromboembolic accident at 1 and 2 months of follow-up. Most patients undergoing electrical cardioversion for atrial fibrillation could benefit from a shorter period of anticoagulation with low-molecular-weight heparins for 1 week if TEE precardioversion and 7 days postcardioversion excludes thrombi and atrial stunning. The management of patients with atrial fibrillation would be greatly simplified.

Thromboprophylaxis for Patients with High-risk Atrial Fibrillation and Flutter Discharged from the Emergency Department.

PubMed

Vinson, David R; Warton, E Margaret; Mark, Dustin G; Ballard, Dustin W; Reed, Mary E; Chettipally, Uli K; Singh, Nimmie; Bouvet, Sean Z; Kea, Bory; Ramos, Patricia C; Glaser, David S; Go, Alan S

2018-03-01

Many patients with atrial fibrillation or atrial flutter (AF/FL) who are high risk for ischemic stroke are not receiving evidence-based thromboprophylaxis. We examined anticoagulant prescribing within 30 days of receiving dysrhythmia care for non-valvular AF/FL in the emergency department (ED). This prospective study included non-anticoagulated adults at high risk for ischemic stroke (ATRIA score ≥7) who received emergency AF/FL care and were discharged home from seven community EDs between May 2011 and August 2012. We characterized oral anticoagulant prescribing patterns and identified predictors of receiving anticoagulants within 30 days of the index ED visit. We also describe documented reasons for withholding anticoagulation. Of 312 eligible patients, 128 (41.0%) were prescribed anticoagulation at ED discharge or within 30 days. Independent predictors of anticoagulation included age (adjusted odds ratio [aOR] 0.89 per year, 95% confidence interval [CI] 0.82-0.96); ED cardiology consultation (aOR 1.89, 95% CI [1.10-3.23]); and failure of sinus restoration by time of ED discharge (aOR 2.65, 95% CI [1.35-5.21]). Reasons for withholding anticoagulation at ED discharge were documented in 139 of 227 cases (61.2%), the most common of which were deferring the shared decision-making process to the patient's outpatient provider, perceived bleeding risk, patient refusal, and restoration of sinus rhythm. Approximately 40% of non-anticoagulated AF/FL patients at high risk for stroke who presented for emergency dysrhythmia care were prescribed anticoagulation within 30 days. Physicians were less likely to anticoagulate older patients and those with ED sinus restoration. Opportunities exist to improve rates of thromboprophylaxis in this high-risk population.

Anticoagulation Quality Assessment in Patients with Nonvalvular Atrial Fibrillation (NVAF) and Comparison with Major Trials of Direct-Acting Oral Anticoagulants

DTIC Science & Technology

2016-04-22

Purpose: The benefits of warfarin anticoagulation therapy are strongly correlated with the ability to maintain patients’ INR goal, known as the time...Rosendaal). Differences in TTR calculations could alter perceptions about the effectiveness of warfarin therapy.

Resolution of massive left atrial appendage thrombi with rivaroxaban before balloon mitral commissurotomy in severe mitral stenosis: A case report and literature review.

PubMed

Li, Yuechun; Lin, Jiafeng; Peng, Chen

2016-12-01

Data on nonvitamin K antagonist oral anticoagulant being used for the treatment of LAA thrombi are limited only in nonvalvular atrial fibrillation. There are no data on the antithrombotic efficacy and safety of nonvitamin K antagonist oral anticoagulant in the resolution of left atrial appendage (LAA) thrombi in patients with rheumatic mitral stenosis. A 49-year-old woman with known rheumatic mitral stenosis and atrial fibrillation was referred for percutaneous transvenous mitral commissurotomy because of progressive dyspnea on exertion over a period of 3 months. Transesophageal echocardiography (TEE) demonstrated a large LAA thrombus protruding into left atria cavity before the procedure. Direct factor Xa (FXa) inhibitor rivaroxaban (20 mg/d) was started for the patient. After 3 weeks of rivaroxaban treatment TEE showed a relevantly decreased thrombus size, and a complete thrombus resolution was achieved after 5 weeks of anticoagulant therapy with the FXa inhibitor. To the best of our knowledge, this is the first documented case of large LAA thrombus resolution with nonvitamin K antagonist oral anticoagulant in severe mitral stenosis, and in which percutaneous transvenous mitral commissurotomy was performed subsequently. The report indicated that rivaroxaban could be a therapeutic option for mitral stenosis patients with LAA thrombus. Further study is required before the routine use of rivaroxaban in patients with rheumatic mitral stenosis and atrial fibrillation.

Oral anticoagulation management in patients with atrial fibrillation undergoing cardiac implantable electronic device implantation.

PubMed

Black-Maier, Eric; Kim, Sunghee; Steinberg, Benjamin A; Fonarow, Gregg C; Freeman, James V; Kowey, Peter R; Ansell, Jack; Gersh, Bernard J; Mahaffey, Kenneth W; Naccarelli, Gerald; Hylek, Elaine M; Go, Alan S; Peterson, Eric D; Piccini, Jonathan P

2017-09-01

Oral anticoagulation (OAC) therapy is associated with increased periprocedural risks after cardiac implantable electronic device (CIED) implantation. Patterns of anticoagulation management involving non-vitamin K antagonist oral anticoagulants (NOACs) have not been characterized. Anticoagulation strategies and outcomes differ by anticoagulant type in patients undergoing CIED implantation. Using the nationwide Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we assessed how atrial fibrillation (AF) patients undergoing CIED implantation were cared for and their subsequent outcomes. Outcomes were compared by oral anticoagulant therapy (none, warfarin, or NOAC) as well as by anticoagulation interruption status. Among 9129 AF patients, 416 (5%) underwent CIED implantation during a median follow-up of 30 months (interquartile range, 24-36). Of these, 60 (14%) had implantation on a NOAC. Relative to warfarin therapy, those on a NOAC were younger (70.5 years [range, 65-77.5 years] vs 77 years [range, 70-82 years]), had less valvular heart disease (15.0% vs 31.3%), higher creatinine clearance (67.3 [range, 59.7-99.0] vs 65.8 [range, 50.0-91.6]), were more likely to have persistent AF (26.7% vs 22.9%), and use concomitant aspirin (51.7% vs 35.2%). OAC therapy was commonly interrupted for CIED in 64% (n = 183 of 284) of warfarin patients and 65% (n = 39 of 60) of NOAC patients. Many interrupted patients received intravenous bridging anticoagulation: 33/183 (18%) interrupted warfarin and 4/39 (10%) interrupted NOAC patients. Thirty-day periprocedure bleeding and stroke adverse events were infrequent. Management of anticoagulation among AF patients undergoing CIED implantation is highly variable, with OAC being interrupted in more than half of both warfarin- and NOAC-treated patients. Bleeding and stroke events were infrequent in both warfarin and NOAC-treated patients. © 2017 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.

Anticoagulation knowledge in patients with atrial fibrillation: An Australian survey.

PubMed

Obamiro, Kehinde O; Chalmers, Leanne; Lee, Kenneth; Bereznicki, Bonnie J; Bereznicki, Luke R E

2018-03-01

Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia in clinical practice, and is associated with a significant medical and economic burden. Anticoagulants reduce the risk of stroke and systemic embolism by approximately two-thirds compared with no therapy. Knowledge regarding anticoagulant therapy can influence treatment outcomes in patients with AF. To measure the level of anticoagulation knowledge in patients with AF taking oral anticoagulants (OACs), investigate the association between patient-related factors and anticoagulation knowledge, and compare these results in patients taking warfarin and direct-acting oral anticoagulant (DOACs). Participants were recruited for an online survey via Facebook. Survey components included the Anticoagulation Knowledge Tool, the Perception of Anticoagulant Treatment Questionnaires (assessing treatment expectations, convenience and satisfaction), a modified Cancer Information Overload scale and the Morisky Medication Adherence Scale. Treatment groups were compared and predictors of OAC knowledge were identified. Participants taking warfarin had a higher knowledge score compared with those taking DOACs (n = 386, 73% ± 13% vs 66% ± 14%, P<.001). Advancing age, type of OAC, health information overload and ease of OAC use (treatment expectation) were significant predictors of knowledge. Treatment expectation, including the belief that OAC treatment would cause bleeding side effects, varied significantly between participants taking warfarin and DOACs (P = .011). The study identified knowledge gaps in patients taking OACs, and these deficiencies appeared to be greater in participants taking DOACs. Knowledge assessment should be integrated into patient counselling sessions to help identify and resolve knowledge deficits. © 2018 John Wiley & Sons Ltd.

A Multilevel Analysis of Real-World Variations in Oral Anticoagulation Initiation for Atrial Fibrillation in Valencia, a European Region.

PubMed

García-Sempere, Aníbal; Bejarano-Quisoboni, Daniel; Librero, Julián; Rodríguez-Bernal, Clara L; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

2017-01-01

Introduction: Beyond clinical trials, clinical practice guidelines, and administrative regulation, treatment decision-making can be influenced by individual and contextual factors. Our goal was to describe variations in the patterns of initiation of anticoagulation therapy in patients with atrial fibrillation by Health Areas (HA) in the region of Valencia in Spain and to quantify the influence of the HAs on variations in treatment choice. Methods: We conducted a population-based retrospective cohort study of all atrial fibrillation patients who started treatment with oral anticoagulants between November 2011 and February 2014 in each of the region's 24 HAs. We described patient and utilization characteristics per HA and initiation patterns over time, and we identified contextual and individual factors associated with differences in initiation patterns. Results: 21,879 patients initiated treatment with an oral anticoagulant in the 24 HAs. Initiation with direct oral anticoagulants (DOAC) in the first year was 14.6%. In November 2013 the ratio was 25.4%, with HA ratios ranging from 3.8 to 57.1%. DOAC-initiating patients had less comorbidity but were more likely to present episodes of previous ischemic stroke, hemorrhagic stroke, or TIA when compared with patients initiating with VKA treatment. Variability among HAs was statistically significant, with the majority of HAs ranking above or below the regional initiation average (ICC ≈ 8%). Conclusion: There was high variability in the percentage of DOAC initiation and in the choice of DOAC among HAs. Interventions aimed to improve DOAC initiation decision-making and to reduce variations should take into account the Health Area component.

A Multilevel Analysis of Real-World Variations in Oral Anticoagulation Initiation for Atrial Fibrillation in Valencia, a European Region

PubMed Central

García-Sempere, Aníbal; Bejarano-Quisoboni, Daniel; Librero, Julián; Rodríguez-Bernal, Clara L.; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

2017-01-01

Introduction: Beyond clinical trials, clinical practice guidelines, and administrative regulation, treatment decision-making can be influenced by individual and contextual factors. Our goal was to describe variations in the patterns of initiation of anticoagulation therapy in patients with atrial fibrillation by Health Areas (HA) in the region of Valencia in Spain and to quantify the influence of the HAs on variations in treatment choice. Methods: We conducted a population-based retrospective cohort study of all atrial fibrillation patients who started treatment with oral anticoagulants between November 2011 and February 2014 in each of the region's 24 HAs. We described patient and utilization characteristics per HA and initiation patterns over time, and we identified contextual and individual factors associated with differences in initiation patterns. Results: 21,879 patients initiated treatment with an oral anticoagulant in the 24 HAs. Initiation with direct oral anticoagulants (DOAC) in the first year was 14.6%. In November 2013 the ratio was 25.4%, with HA ratios ranging from 3.8 to 57.1%. DOAC-initiating patients had less comorbidity but were more likely to present episodes of previous ischemic stroke, hemorrhagic stroke, or TIA when compared with patients initiating with VKA treatment. Variability among HAs was statistically significant, with the majority of HAs ranking above or below the regional initiation average (ICC ≈ 8%). Conclusion: There was high variability in the percentage of DOAC initiation and in the choice of DOAC among HAs. Interventions aimed to improve DOAC initiation decision-making and to reduce variations should take into account the Health Area component. PMID:28883793

Impact of CHA2DS2VASc Score on Candidacy for Anticoagulation in Patients With Atrial Fibrillation: A Multi-payer Analysis.

PubMed

Patel, Aarti A; Nelson, Winnie W; Schein, Jeff

2016-10-01

The purpose of this study is to report on the effect of using CHA 2 DS 2 VASc (congestive heart failure, hypertension, age ≥75 years [doubled], type 1 or type 2 diabetes mellitus, stroke or transient ischemic attack or thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) rather than CHADS 2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke) to determine candidacy for anticoagulant prophylaxis in insured patients with atrial fibrillation (AF). Six administrative claims databases that included medical and pharmacy claims for patients aged ≥18 years with a new or existing diagnosis of AF and patient outcomes assessed for 1 year after diagnosis were analyzed. Retrospective health plan data analyses were performed using a software tool (Anticoagulant Quality Improvement Analyzer). Study measures included stroke risk (identified by CHADS 2 and CHA 2 DS 2 VASc scores), bleeding risk (identified by the Anticoagulation and Risk Factors in Atrial Fibrillation score), and anticoagulant use. A total of 115,906 patients with AF (range of mean ages among the 6 databases, 56-79 years) met the inclusion criteria. All ranges reported represent the minimum and maximum values among the 6 databases. Using the CHA 2 DS 2 VASc compared with the CHADS 2 index to assess stroke risk resulted in a 23% to 32% increase in patients considered potential candidates for anticoagulant prophylaxis. This translated to a 38% to 114% increase in the number of ostensibly undertreated patients. Among patients with high stroke and low bleeding risk, 18% to 28% more patients were considered potential candidates for anticoagulation treatment using CHA 2 DS 2 VASc compared with CHADS 2 , or a 57% to 151% increase in the number of undertreated patients. Use of the CHA 2 DS 2 VASc score to determine the risk of stroke increased the number of AF patients for whom oral anticoagulation would be recommended. Additional research is needed to determine whether this paradigm shift to greater use of oral anticoagulants improves patient outcomes. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

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

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.

Current and Emerging Uses of Insertable Cardiac Monitors: Evaluation of Syncope and Monitoring for Atrial Fibrillation.

PubMed

Tomson, Todd T; Passman, Rod

Insertable cardiac monitors (ICMs) have provided clinicians with a superb tool for assessing infrequent or potentially asymptomatic arrhythmias. ICMs have shown their usefulness in the evaluation of unexplained syncope, providing high diagnostic yields in a cost-effective manner. While unexplained syncope continues to be the most common reason for their use, ICMs are increasingly being used for the monitoring of atrial fibrillation (AF). Recent trials have demonstrated that a substantial proportion of patients with cryptogenic stroke have AF detected only by the prolonged monitoring provided by ICMs. A particularly promising and emerging use for ICMs is in the management of anticoagulation in patients with known paroxysmal AF. The introduction in recent years of ICMs with automatic AF detection algorithms and continuous remote monitoring in combination with novel oral anticoagulants have opened the door for targeted anticoagulation guided by remote monitoring, a strategy that has recently shown promise in pilot studies of this technique. While further research is needed before official recommendations can be given, this use of ICMs opens exciting new possibilities for personalized medicine that could potentially reduce bleeding risk and improve quality of life in patients with atrial fibrillation.

Adherence and Coagulation Assays in Dabigatran-treated Patients With Atrial Fibrillation

ClinicalTrials.gov

2017-09-12

Atrial Fibrillation; Medication Adherence; Blood Coagulation Tests; Anticoagulants; Circulating, Hemorrhagic Disorder; Drug Effect; Drug Use; Drug Toxicity; Drug Intolerance; Blood Clot; Blood Coagulation Disorder; Laboratory Problem; Bleeding; Thrombosis

Percutaneous left atrial appendage occlusion in atrial fibrillation patients with a contraindication to oral anticoagulation: a focused review.

PubMed

Nishimura, Marin; Sab, Shiv; Reeves, Ryan R; Hsu, Jonathan C

2017-12-08

Stroke is the most feared complication of atrial fibrillation (AF). Although oral anticoagulation with non-vitamin K antagonist and non-vitamin K antagonist oral anticoagulants (NOACs) have been established to significantly reduce risk of stroke, real-world use of these agents are often suboptimal due to concerns for adverse events including bleeding from both patients and clinicians. Particularly in patients with previous serious bleeding, oral anticoagulation may be contraindicated. Left atrial appendage occlusion (LAAO), mechanically targeting the source of most of the thrombi in AF, holds an immense potential as an alternative to OAC in management of stroke prophylaxis. In this focused review, we describe the available evidence of various LAAO devices, detailing data regarding their use in patients with a contraindication for oral anticoagulation. Although some questions of safety and appropriate use of these new devices in patients who cannot tolerate anticoagulation remain, LAAO devices offer a significant step forward in the management of patients with AF, including those patients who may not be able to be prescribed OAC at all. Future studies involving patients fully contraindicated to OAC are warranted in the era of LAAO devices for stroke risk reduction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

[Consensus statement: Management of oral anticoagulation for stroke prevention in patients with nonvalvular atrial fibrillation].

PubMed

Helms, Thomas Maria; Silber, Sigmund; Schäfer, Andreas; Masuhr, Florian; Palm, Frederick; Darius, Harald; Schrör, Karsten; Bänsch, Dietmar; Bramlage, Peter; Hankowitz, Johannes; Karle, Christoph A; Stargardt, Tom; Weil, Joachim; Geller, Johann Christoph

2016-09-01

With the introduction of edoxaban last year in Germany, four nonvitamin K antagonist oral anticoagulants are now available for stroke prevention in patients with nonvalvular atrial fibrillation. These novel oral anticoagulants (NOAC) represent an attractive new option compared to vitamin K antagonists (e.g., warfarin or phenprocoumon) due to simple use and fewer interactions with other drugs or food. Therefore, no INR monitoring and dosage adjustments are required for NOAC. The compelling clinical advantage of NOAC is the dramatic risk reduction of hemorhagic stroke and intracranial bleeding compared to current standard. In addition, total mortality is significantly reduced by 10 %. These effects are demonstrated for all four NOAC (dabigatran, rivaroxaban, apixaban and edoxaban). Therefore, current national and international guidelines recommend NOAC as the preferred option or at least as an attractive alternative compared to the former standard of vitamin K antagonists. The economic impact and reimbursement by Statutory Health Insurance (GKV) is of major importance for treatment in an outpatient setting. For apixaban and edoxaban, an additional benefit was granted by the institution of G‑BA and IQWiG in this clinical setting, whereas dabigatran and rivaroxaban were not assessed due to market entrance prior to 2011 before the AMNOG procedure was initiated. The members of this consensus paper recommend NOAC as the preferred option for patients with nonvalvular atrial fibrillation who are currently not treated with anticoagulant drugs in spite of clear indication for anticoagulation. For new patients with nonvalvular fibrillation, it should be decided on an individual basis which treatment option is adequate for the patient with their respective comorbidities.

Coherex WAVECREST I Left Atrial Appendage Occlusion Study

ClinicalTrials.gov

2015-01-13

Non-valvular Paroxysmal, Persistent, or Permanent Atrial Fibrillation; LAA Anatomy Amenable to Treatment by Percutaneous Technique; Anticoagulation Indication for Potential Thrombus Formation in the Left Atrium

Triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a viewpoint.

PubMed

Gwyn, Jennifer C V; Thomas, Mark R; Kirchhof, Paulus

2017-07-01

Patients undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy to reduce the risk of subsequent myocardial infarction (MI) and stent thrombosis. Approximately 5-10% of patients undergoing PCI also have atrial fibrillation (AF). Patients with AF have an additional requirement for anticoagulation, as dual antiplatelet therapy alone is insufficient to adequately reduce the risk of stroke in patients with AF. However, it is now well established that combining anticoagulants with dual antiplatelet therapy also causes a significant increase in the risk of bleeding. Hence, there is great interest in discovering the optimal blend of antiplatelet therapy and oral anticoagulation in this situation, aiming to reduce the risk of stent thrombosis, recurrent MI, and stroke, while also minimizing the risk of bleeding. Recent studies have experimented with combining oral anticoagulation with a single antiplatelet agent, rather than combining oral anticoagulation with dual antiplatelet therapy. These studies show that this reduces the risk of bleeding but are underpowered to determine whether this still provides as much cardiovascular benefit. This review summarizes the currently available evidence on this topic and highlights the key questions that remain to be answered including ongoing clinical trials in the field. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Comparison of estimated glomerular filtration rate equations for dosing new oral anticoagulants in patients with atrial fibrillation.

PubMed

Manzano-Fernández, Sergio; Andreu-Cayuelas, José M; Marín, Francisco; Orenes-Piñero, Esteban; Gallego, Pilar; Valdés, Mariano; Vicente, Vicente; Lip, Gregory Y H; Roldán, Vanessa

2015-06-01

New oral anticoagulants require dosing adjustment according to renal function. We aimed to determine discordance in hypothetical recommended dosing of these drugs using different estimated glomerular filtration rate equations in patients with atrial fibrillation. Cross-sectional analysis of 910 patients with atrial fibrillation and an indication for oral anticoagulation. The glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations. For dabigatran, rivaroxaban, and apixaban we identified dose discordance when there was disagreement in the recommended dose based on different equations. Among the overall population, relative to Cockcroft-Gault, discordance in dabigatran dosage was 11.4% for Modification of Diet in Renal Disease and 10% for Chronic Kidney Disease Epidemiology Collaboration, discordance in rivaroxaban dosage was 10% for Modification of Diet in Renal Disease and 8.5% for the Chronic Kidney Disease Epidemiology Collaboration. The lowest discordance was observed for apixaban: 1.4% for Modification of Diet in Renal Disease and 1.5% for the Chronic Kidney Disease Epidemiology Collaboration. In patients with Cockcroft-Gault<60mL/min or elderly patients, discordances in dabigatran and rivaroxaban dosages were higher, ranging from 13.2% to 30.4%. Discordance in apixaban dosage remained<5% in these patients. Discordance in new oral anticoagulation dosages using different equations is frequent, especially among elderly patients with renal impairment. This discordance was higher in dabigatran and rivaroxaban dosages than in apixaban dosages. Further studies are needed to clarify the clinical importance of these discordances and the optimal anticoagulant dosages depending on the use of different equations to estimate renal function. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Assessment of anticoagulation treatments in non-valvular atrial fibrillation patients diagnosed in a basic health area.

PubMed

Aguilera Alcaraz, Beatriz M; Abellán Huerta, José; Carbayo Herencia, Julio Antonio; Ariza Copado, Consuelo; Hernández Menárguez, Fernando; Abellán Alemán, José

Atrial fibrillation (AF) is the most common cardiac arrhythmia. To assess the need for anticoagulation is essential for its management. Our objective was to investigate whether the indication of anticoagulation was adequate in patients diagnosed with non-valvular AF, given the CHA2-DS2-VASc scale, measuring the International Normalizad Ratio range (INR) in patients treated with anti-vitamin K drugs. This is an observational and cross sectional study. 232 patients with atrial fibrillation were included. We analyzed demographic, the CHA2-DS2-VASc and HAS-BLED variables, the treatment and INR values for 6 consequentive months. The confrontation of variables was performed using chi-square and Mantel-Haenzel test. The prevalence of AF was 1.05%. The 88.4% had CHA2-DS2-VASc ≥ 2. The 71.1% were taking anticoagulants, of which 58.2% were under antivitamin k. The 46.7% of patients taking antivitamin K, presented inadequate range of INR. There was a greater prescription of antivitamin k in patients with persistent or permanent AF compared to the paroxysmal form (62.8 vs. 37.2% p<.001). The use of drugs that increase bleeding was associated with a worse control of INR after adjustment for the main variables of clinical relevance (odds ratio 2.17 [1.02-4.59], p=.043). The level of anticoagulation with antivitamin K was inadequate in our sample, despite a proper follow up and adherence to treatment. Patients with paroxysmal AF received less antivitamin K than those with persistent/permanent AF. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

PubMed

DiMarco, John P; Flaker, Gregory; Waldo, Albert L; Corley, Scott D; Greene, H Leon; Safford, Robert E; Rosenfeld, Lynda E; Mitrani, Gladys; Nemeth, Margit

2005-04-01

Stroke and systemic thromboembolism are serious problems for patients with atrial fibrillation (AF), but their incidence can be substantially reduced by appropriate anticoagulation. Bleeding is the major complication of anticoagulant treatment, and the relative risks for bleeding vs stroke must be considered when starting anticoagulation. The AFFIRM trial included patients with AF and at least one risk factor for stroke, randomly assigning them to either a rate-control or rhythm-control strategy. All patients were initially treated with warfarin. The incidence of protocol-defined major and minor bleeding was documented during follow-up. Variables associated with bleeding were determined using a Cox proportional hazards model, using baseline and time-dependent covariates. The 4060 patients in the AFFIRM trial were followed for an average of 3.5 years. Major bleeding occurred in 260 patients, an annual incidence of approximately 2% per year, with no significant difference between the rate-control and rhythm-control groups. Increased age, heart failure, hepatic or renal disease, diabetes, first AF episode, warfarin use, and aspirin use were significantly associated with major bleeding. Minor bleeding was common in both treatment arms, with 738 patients reporting this problem in one or more visits. Bleeding is a significant problem that complicates management of patients with AF. Risk factors for bleeding can be identified, and knowledge of these risk factors can be used to plan therapy.

[ESC guidelines on atrial fibrillation 2016 : Summary of the most relevant recommendations and modifications].

PubMed

Eckardt, L; Häusler, K G; Ravens, U; Borggrefe, M; Kirchhof, P

2016-12-01

The first European Society of Cardiology (ESC) guidelines on atrial fibrillation (AF) developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) were published in August 2016. These guidelines replace the revised guidelines from 2012 and contain some interesting new aspects. The topics range from the pathophysiology through diagnostics, therapy and stroke prevention up to special clinical situations, such as atrial fibrillation in cardiopathy, sport and pregnancy. Early screening, patient informed consent, individualized therapy and the modification of factors promoting atrial fibrillation are of particular importance. The guidelines recommend the establishment of AF heart teams, containing specialists from various disciplines. The guidelines also underline the importance of non-vitamin K‑dependent oral anticoagulants (NOAC) for stroke prevention compared to standard anticoagulants with vitamin K antagonists. For symptomatic and especially paroxysmal atrial fibrillation, the guidelines emphasize the importance of an antiarrhythmic treatment with catheter ablation and/or pharmaceutical antiarrhythmic therapy in addition to a frequency regulating therapy.

Use of Warfarin at Discharge Among Acute Ischemic Stroke Patients With Nonvalvular Atrial Fibrillation in China.

PubMed

Yang, Xiaomeng; Li, Zixiao; Zhao, Xingquan; Wang, Chunjuan; Liu, Liping; Wang, Chunxue; Pan, Yuesong; Li, Hao; Wang, David; Hart, Robert G; Wang, Yilong; Wang, Yongjun

2016-02-01

Guidelines recommend oral anticoagulation for ischemic stroke patients with atrial fibrillation, and previous studies have shown the underuse of anticoagulation for these patients in China. We sought to explore the underlying reasons and factors that currently affect the use of warfarin in China. From June 2012 to January 2013, 19 604 patients with acute ischemic stroke were admitted to 219 urban hospitals voluntarily participating in the China National Stroke Registry II. Multivariable logistic regression models using the generalized estimating equation method were used to identify patient/hospital factors independently associated with warfarin use at discharge. Among the 952 acute ischemic stroke patients with nonvalvular atrial fibrillation, 19.4% were discharged on warfarin. The risk of bleeding (52.8%) and patient refusal (31.9%) were the main reasons for not prescribing anticoagulation. Larger/teaching hospitals were more likely to prescribe warfarin. Older patients, heavy drinkers, patients with higher National Institutes of Health Stroke Scale score on admission were less likely to be given warfarin, whereas patients with history of heart failure and an international normalized ratio between 2.0 and 3.0 during hospitalization were significantly associated with warfarin use at discharge. The rate of warfarin use remains low among patients with ischemic stroke and known nonvalvular atrial fibrillation in China. Hospital size and academic status together with patient age, heart failure, heavy alcohol drinking, international normalized ratio in hospital, and stroke severity on admission were each independently associated with the use of warfarin at discharge. There is much room for improvement for secondary stroke prevention in nonvalvular atrial fibrillation patients in China. © 2015 American Heart Association, Inc.

Contemporary approach to stroke prevention in atrial fibrillation: Risks, benefits, and new options.

PubMed

Stock, Jonathan; Malm, Brian J

2018-04-04

Atrial fibrillation is a common diagnosis affecting nearly 3 million adults in the United States. Morbidity and mortality in these patients is driven largely by the associated increased risk of thromboembolic complications, especially stroke. Atrial fibrillation is a stronger risk factor than hypertension, coronary disease, or heart failure and is associated with an approximately five-fold increased risk. Mitigating stroke risk can be challenging and requires accurate assessment of stroke risk factors and careful selection of appropriate therapy. Anticoagulation, including the more recently introduced direct oral anticoagulants, is the standard of care for most patients. In addition, emerging non-pharmacologic mechanical interventions are playing an expanding role in reducing stroke risk in select patients. In this review we highlight the current approach to stroke risk stratification in atrial fibrillation and discuss in detail the mechanism, risks, and benefits of current and evolving therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

Does sex affect anticoagulant use for stroke prevention in nonvalvular atrial fibrillation? The prospective global anticoagulant registry in the FIELD-Atrial Fibrillation.

PubMed

Lip, Gregory Y H; Rushton-Smith, Sophie K; Goldhaber, Samuel Z; Fitzmaurice, David A; Mantovani, Lorenzo G; Goto, Shinya; Haas, Sylvia; Bassand, Jean-Pierre; Camm, Alan John; Ambrosio, Giuseppe; Janský, Petr; Al Mahmeed, Wael; Oh, Seil; van Eickels, Martin; Raatikainen, Pekka; Steffel, Jan; Oto, Ali; Kayani, Gloria; Accetta, Gabriele; Kakkar, Ajay K

2015-03-01

Among patients with atrial fibrillation (AF), women are at higher risk of stroke than men. Using prospective cohort data from a large global population of patients with nonvalvular AF, we sought to identify any differences in the use of anticoagulants for stroke prevention in women and men. This was a prospective multicenter observational registry with 858 randomly selected sites in 30 countries. A total of 17 184 patients with newly diagnosed (≤6 weeks) nonvalvular AF and ≥1 additional investigator-defined stroke risk factor(s) were recruited (March 2010 to June 2013). The main outcome measure was the use of anticoagulants (vitamin K antagonists, factor Xa inhibitors, and direct thrombin inhibitors) for stroke prevention at AF diagnosis. Of 17 184 patients enrolled, 43.8% were women. More women than men were at moderate-to-high risk of stroke (CHADS2 score ≥2: 65.1% versus 54.7%). Rates of anticoagulant use were not different overall (60.9% of men versus 60.8% of women) and in patients with a CHADS2 score ≥2 (adjusted odds ratio for women versus men, 1.00; 95% confidence interval, 0.92-1.09). In patients at low risk (CHA2DS2-VASc of 0 in men and 1 in women), 41.8% of men and 41.1% of women received an anticoagulant. In patients at high risk (CHA2DS2-VASc score ≥2), 35.4% of men and 38.4% of women did not receive an anticoagulant. These contemporary global data show that anticoagulant use for stroke prevention is no different in men and women with nonvalvular AF. Thromboprophylaxis was, however, suboptimal in substantial proportions of men and women, with underuse in those at moderate-to-high risk of stroke and overuse in those at low risk. http://www.clinicaltrials.gov. Unique identifier: NCT01090362. © 2015 American Heart Association, Inc.

Adherence to recommendations of the Therapeutic Positioning Report about treatment with oral anticoagulants in elderly patients with atrial fibrillation. The ESPARTA study.

PubMed

Suárez Fernández, Carmen; Mostaza, Jose María; Castilla Guerra, Luis; Cantero Hinojosa, Jesus; Suriñach, Josep Maria; Acosta de Bilbao, Fernando; Tamarit, Juan José; Diaz Diaz, José Luis; Hernandez, Jose Luis; Cazorla, Daniel; Ràfols, Carles

2017-10-06

To evaluate the adherence to the recommendations in clinical practice performed by the Therapeutic Positioning Report (TPR) of the Spanish Agency of Medicines and Sanitary Products about the treatment with oral anticoagulants in patients aged≥75 years old with nonvalvular atrial fibrillation (NVAF) treated in Internal Medicine departments in Spain. Observational, cross-sectional and multicenter study in which 837 patients aged≥75 years old with NVAF, with stable treatment with oral anticoagulants at least 3 months before inclusion, and that had started treatment with oral anticoagulants before the inclusion period were included. Mean age was 83.0±5.0 years old, mean CHADS 2 score 3.2±1.2, mean CHA 2 DS 2 -VASc score 5.0±1.4, and mean HAS-BLED score 2.1±0.9. A percentage of 70.8 of patients were treated with vitamin K antagonists (VKA) and the rest of patients with direct oral anticoagulants (DOACs). A percentage of 65.6 of patients treated with VKA did not follow the recommendations made by the TPR compared with 43.0% of patients treated with DOACs (P<.0001). In the case of VKA, the main reason for being considered as not appropriate according to the TPR was having poor control of anticoagulation and not switching to DOACs, whereas in the case of DOACs, it was not receiving the adequate dose according to the TPR. In a high proportion of anticoagulated elderly patients with NVAF in Spain, the recommendations performed by the TPR are not followed, particularly with VKA, since patients are not switched to DOACs despite time in therapeutic range. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

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.

Apixaban: Effective and Safe in Preventing Thromboembolic Events in Patients with Atrial Fibrillation and Renal Failure.

PubMed

Cortese, Francesca; Scicchitano, Pietro; Gesualdo, Michele; Ricci, Gabriella; Carbonara, Santa; Franchini, Carlo; Pia Schiavone, Brigida Immacolata; Corbo, Filomena; Ciccone, Marco Matteo

2017-11-17

Thromboembolic events, principally stroke, represent one of the leading causes of morbidity and mortality among subjects with atrial fibrillation. Chronic kidney disease determines a further increase of thromboembolic events, bleeding and mortality and complicates the pharmacological management of patients with atrial fibrillation, mainly due to the side effects of antiarrhythmic and anticoagulant drugs with renal excretion. Apixaban is a new oral anticoagulant characterized by good bioavailability and renal elimination accounting for only 25%, showing a safety profile and effectiveness in patients with renal impairment. In this manuscript, we reviewed literature data on the use of apixaban in the management of non-valvular atrial fibrillation in patients with renal failure, in order to clarify an often-debated topic in clinical practice. A PubMed search was performed on the terms atrial fibrillation, apixaban and renal failure with the aim of identifying relevant manuscripts, large randomized clinical trials, meta-analyses, and current guidelines. Literature data show that apixaban could represent an interesting alternative to warfarin and other selective antagonists of coagulation factors in patients with impaired renal function. About the risk of major bleeding, apixaban appears to be safer than warfarin in the presence of any degree of renal failure. Apixaban show to be an effective anticoagulant in patients with atrial fibrillation, even superior to warfarin in reducing the risk of stroke and systemic embolism regardless of the presence of renal insufficiency. Moreover, Food and Drug Administration allows the use of apixaban in patients with end stage renal disease on hemodialysis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

New oral anticoagulants--a review.

PubMed

Ghanima, Waleed; Atar, Dan; Sandset, Per Morten

2013-10-01

Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been approved in Norway. The aim of this article is to provide an overview of the mechanisms of action, the most important indications and practical advice on the use of these drugs. The review is based on published phase 3 studies, a literature search in PubMed and the authors' clinical experience. Indications for use of the new anticoagulants include thromboprophylaxis after total hip and knee replacement surgery (all three), prevention of stroke and systemic embolism in non-valvular atrial fibrillation (all three), treatment of acute venous thrombosis and secondary prophylaxis after venous thrombosis (currently only rivaroxaban). For the aforementioned indications, these drugs have proven to be non-inferior to standard established anticoagulation therapy. For atrial fibrillation, all three drugs have also shown a lower incidence of intracranial bleeding compared with standard treatment. It is important to limit the use of these drugs to approved indications, to select patients who show good compliance, to rule out contraindications and to identify drug interactions. Monitoring of coagulation is not required, but patients should be followed up regularly to detect conditions that may lead to changes in the expected efficacy or safety.

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.

External validity of the ARISTOTLE trial in real-life atrial fibrillation patients.

PubMed

Hägg, Lovisa; Johansson, Cecilia; Jansson, Jan-Håkan; Johansson, Lars

2014-10-01

Our primary objective was to determine the proportion of patients with atrial fibrillation (AF) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant, the ARISTOTLE trial. A secondary objective was to describe the reasons for trial ineligibility. We performed a cross-sectional study of an unselected population including 2274 patients in Skellefteå, Sweden with at least one verified episode of AF on or before December 31, 2010. Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines. The enrollment criteria from the ARISTOTLE trial were extracted from the original publication and applied to the population. Among all patients with AF, 1579 were classified as suitable for anticoagulant treatment. Of these, only 658 patients (42%) were eligible for participation in the ARISTOTLE trial. Among the 921 patients ineligible for participation, 498 did not meet the ECG criteria, 272 had psychosocial problems, and in addition, 78 patients were excluded due to both of these criteria. Our study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial. The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life. © 2014 John Wiley & Sons Ltd.

Detection and management of atrial fibrillation after cryptogenic stroke or embolic stroke of undetermined source.

PubMed

Sanna, Tommaso; Ziegler, Paul D; Crea, Filippo

2018-03-01

Cryptogenic stroke (CS) and embolic stroke of unknown source (ESUS) represent a major challenge to healthcare systems worldwide. Atrial fibrillation (AF) is commonly found after CS or ESUS. Independent of the mechanism of the index CS or ESUS, detection of AF in these patients offers the opportunity to reduce the risk of stroke recurrence by prescribing an anticoagulant instead of aspirin. The detection of AF may be pursued with different monitoring strategies. Comparison of monitoring strategies should take into account that AF detection rates reported in published studies, and then pooled in meta-analyses, are not only a function of the monitoring strategy itself, but also depend on patient-related, device-related, and study design-related factors. Once AF is found, the decision to anticoagulate a patient should be made on the basis of AF burden and the baseline risk of the patient. Empirical anticoagulation in patients with ESUS and no evidence of AF is an intriguing but still-unproven strategy and therefore should not be adopted outside of randomized clinical trials. © 2018 Wiley Periodicals, Inc.

Values and preferences in oral anticoagulation in patients with atrial fibrillation, physicians' and patients' perspectives: protocol for a two-phase study.

PubMed

Alonso-Coello, Pablo; Montori, Victor M; Solà, Ivan; Schünemann, Holger J; Devereaux, Philipe; Charles, Cathy; Roura, Mercè; Díaz, M Gloria; Souto, Juan Carlos; Alonso, Rafael; Oliver, Sven; Ruiz, Rafael; Coll-Vinent, Blanca; Diez, Ana Isabel; Gich, Ignasi; Guyatt, Gordon

2008-10-27

Oral anticoagulation prevents strokes in patients with atrial fibrillation but, for reasons that remain unclear, less than 40% of all patients with atrial fibrillation receive warfarin. The literature postulates that patient and clinician preferences may explain this low utilization. The proposed research seeks to answer the following questions: i) When assessed systematically, do patients' and clinicians' preferences explain the utilization of warfarin to prevent strokes associated with atrial fibrillation? ii) To what extent do patients' and clinicians' treatment preferences differ? iii) What factors explain any differences that exist in treatment preferences between patients and clinicians? To answer these questions we will conduct a two-phase study of patient and clinician preferences for health states and treatments. In the first phase of this study we will conduct structured interviews to determine their treatment preferences for warfarin vs. aspirin to prevent strokes associated with atrial fibrillation using the probability trade-off technique. In the same interview, we will conduct preference-elicitation exercises using the feeling thermometer to identify the utilities that patients place on taking medication (warfarin and aspirin), and on having a mild stroke, a severe stroke, and a major bleed. In the second phase of the study we will convene focus groups of clinicians and patients to explore their answers to the exercises in the first phase. This is a study of patient and clinician preferences for health states and treatments. Because of its clinical importance and our previous work in this area, we will conduct our study in the clinical context of the decision to use antithrombotic agents to reduce the risk of stroke in patients with non-valvular chronic atrial fibrillation.

[Thromboembolism prophylaxis in old age].

PubMed

Röhrig, Gabriele; Kolb, Gerald

2018-04-01

Anticoagulation in geriatric patients is challenging regarding the risk of bleeding complications and thromboembolic problems. Age, comorbidities, such as renal insufficiency and polymedication have a vital impact on bleeding and thromboembolic risks; however, age is not an exclusion criterion for withholding anticoagulation. Age is the main risk factor for deep vein thrombosis and atrial fibrillation becomes more relevant with aging. Older patients with atrial fibrillation have a particularly high risk of having a stroke. Therefore, very old patients benefit particularly from oral anticoagulation because the risk of bleeding is outweighed by the clinical benefit of stroke prevention. Risk of bleeding and thromboembolic problems can be easily assessed by established diagnostic tools. This article reviews the epidemiology of thromboembolic problems in the aged as well as current diagnostic and therapeutic steps for primary and secondary prevention.

[Evaluation of the quality control of anticoagulation in patients with atrial fibrillation in a Primary Health Care Area of Madrid].

PubMed

Habashneh Sánchez, S; Abad Díaz, I; Tinajero Valle, C P; Cortés Palmero, A; Lobón Agúndez, M C; Muñoz Fernández, C

2016-01-01

To calculate the time in therapeutic range (TTR), as well as the scores on the CHADS2 scale in anticoagulated patients with non-valvular atrial fibrillation, attending the Primary Care Health Centre of Aravaca. Basic health area of Aravaca (Madrid). Retrospective observational study. The Community of Madrid provides a list of patients with non-valvular atrial fibrillation and on anticoagulant therapy in the centre. Excluding those with less than 8 INRs, who began treatment after January 2011, interrupted by inter-current treatment or had cancer or coagulopathy. The study period is from 1 January 2012 to 1 January 2013. The TTR (fraction of INRs in range) was the primary endpoint. The score was also calculated on the CHADS2 scale. A value of 56.28% TTR (59.5-53.1) was obtained from a sample of 963 INRs. Just over half (52%) of patients had a TTR<60%. There were 65 patients with a mean age of 80±7.5 years. The distribution of risk factors for the CHADS2 scale was: Heart failure 18.5%; hypertension 80%; diabetes 29.2%, and embolic events 18.5%. The results of our sample TTR is suboptimal (<60%), which implies an increased risk for embolic episodes and increased likelihood of bleeding. We need to incorporate into our clinical practice an objective measure of the quality of anticoagulation in order to identify poorly controlled patients and introduce corrective measures. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

The business case for quality improvement: oral anticoagulation for atrial fibrillation.

PubMed

Rose, Adam J; Berlowitz, Dan R; Ash, Arlene S; Ozonoff, Al; Hylek, Elaine M; Goldhaber-Fiebert, Jeremy D

2011-07-01

The potential to save money within a short time frame provides a more compelling "business case" for quality improvement than merely demonstrating cost-effectiveness. Our objective was to demonstrate the potential for cost savings from improved control in patients anticoagulated for atrial fibrillation. Our population consisted of 67 077 Veterans Health Administration patients anticoagulated for atrial fibrillation between October 1, 2006, and September 30, 2008. We simulated the number of adverse events and their associated costs and utilities, both before and after various degrees of improvement in percent time in therapeutic range (TTR). The simulation had a 2-year time horizon, and costs were calculated from the perspective of the payer. In the base-case analysis, improving TTR by 5% prevented 1114 adverse events, including 662 deaths; it gained 863 quality-adjusted life-years and saved $15.9 million compared with the status quo, not accounting for the cost of the quality improvement program. Improving TTR by 10% prevented 2087 events, gained 1606 quality-adjusted life-years, and saved $29.7 million. In sensitivity analyses, costs were most sensitive to the estimated risk of stroke and the expected stroke reduction from improved TTR. Utilities were most sensitive to the estimated risk of death and the expected mortality benefit from improved TTR. A quality improvement program to improve anticoagulation control probably would be cost-saving for the payer, even if it were only modestly effective in improving control and even without considering the value of improved health. This study demonstrates how to make a business case for a quality improvement initiative.

The economics of atrial fibrillation: a time for review and prioritization.

PubMed

Cadilhac, Dominique A

2012-08-01

Stroke associated with atrial fibrillation may occur in up to one third of people who experience an ischemic event, and results in greater stroke severity and poorer health outcomes. The ageing population in developed and developing countries will lead to an increase in the prevalence of atrial fibrillation in society. Detecting people who have atrial fibrillation and ensuring optimal prevention management is essential for reducing the burden of stroke worldwide. There is evidence that use of anticoagulants is inadequate in primary and secondary prevention of stroke. New anticoagulants that have fewer side effects and population screening tools are available. However, there is little information available about the cost-effectiveness of these new options for atrial fibrillation detection and stroke prevention management over current practice. Since resources for spending in health are limited, it is essential that formal economic analyses are undertaken to ensure there are informed and evidence-based decisions on where to best invest stroke prevention resources. It is essential that renewed efforts in the area of atrial fibrillation and options for stroke prevention are undertaken within the public health research community. © 2012 The Author. International Journal of Stroke © 2012 World Stroke Organization.

Efficacy and Safety of Oral Anticoagulants Versus Aspirin for Patients With Atrial Fibrillation

PubMed Central

Zhang, Jing-Tao; Chen, Ke-Ping; Zhang, Shu

2015-01-01

Abstract The purpose of this study was to perform a meta-analysis comparing the effectiveness and safety of anticoagulation to antiplatelet therapy for the prevention of thromboembolic events in patients with atrial fibrillation (AF). MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched for studies published through May 31, 2014. Randomized controlled trials comparing anticoagulants (warfarin) and antiplatelet therapy in patients with AF were included. The primary outcomes were the rates of stroke and systemic embolism. Secondary outcomes included the rates of hemorrhage/major bleeding and death. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Nine reports of 8 trials that enrolled 4363 patients (2169 patients received anticoagulation and 2194 antiplatelet therapy) were included. All of the studies compared adjusted-dose warfarin or with aspirin, and the majority of the patients were >70 years of age. Anticoagulants were titrated to an international normalized ratio (INR) of 2.0 to 4.5, and aspirin was administered at a dosage of 75 to 325 mg/d. Death occurred in 206 participants treated with an anticoagulant and 229 participants treated with antiplatelet therapy. There was no significant difference in the overall stroke rate between the groups (OR = 0.667, 95% CI 0.426–1.045, P = 0.08); however, patients with nonrheumatic AF (NRAF) treated with an anticoagulant had a lower risk of stroke (OR = 0.557, 95% CI 0.411–0.753, P < 0.001). Anticoagulants were associated with a lower risk of embolism (OR = 0.616, 95% CI = 0.392–0.966, P = 0.04), and this finding persisted in patients with NRAF (OR = 0.581, 95% CI 0.359–0.941, P = 0.03). No significant difference in the rate of hemorrhage/major bleeding was noted (OR = 1.497, 95% CI 0.730–3.070, P = 0.27), and this finding persisted on subgroup analysis. Anticoagulants appear to be more effective than aspirin in preventing embolisms in patients with AF, as the risk of bleeding is not increased. PMID:25634169

Impact of Variations in Kidney Function on Nonvitamin K Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Recent Acute Heart Failure.

PubMed

Andreu-Cayuelas, José M; Pastor-Pérez, Francisco J; Puche, Carmen M; Mateo-Martínez, Alicia; García-Alberola, Arcadio; Flores-Blanco, Pedro J; Valdés, Mariano; Lip, Gregory Y H; Roldán, Vanessa; Manzano-Fernández, Sergio

2016-02-01

Renal impairment and fluctuations in renal function are common in patients recently hospitalized for acute heart failure and in those with atrial fibrillation. The aim of the present study was to evaluate the hypothetical need for dosage adjustment (based on fluctuations in kidney function) of dabigatran, rivaroxaban and apixaban during the first 6 months after hospital discharge in patients with concomitant atrial fibrillation and heart failure. An observational study was conducted in 162 patients with nonvalvular atrial fibrillation after hospitalization for acute decompensated heart failure who underwent creatinine determinations during follow-up. The hypothetical recommended dosage of dabigatran, rivaroxaban and apixaban according to renal function was determined at discharge. Variations in serum creatinine and creatinine clearance and consequent changes in the recommended dosage of these drugs were identified during 6 months of follow-up. Among the overall study population, 44% of patients would have needed dabigatran dosage adjustment during follow-up, 35% would have needed rivaroxaban adjustment, and 29% would have needed apixaban dosage adjustment. A higher proportion of patients with creatinine clearance < 60 mL/min or with advanced age (≥ 75 years) would have needed dosage adjustment during follow-up. The need for dosage adjustment of nonvitamin K oral anticoagulants during follow-up is frequent in patients with atrial fibrillation after acute decompensated heart failure, especially among older patients and those with renal impairment. Further studies are needed to clarify the clinical importance of these needs for drug dosing adjustment and the ideal renal function monitoring regime in heart failure and other subgroups of patients with atrial fibrillation. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Practical recommendations for the choice of anticoagulants in the management of patients with atrial fibrillation on ibrutinib.

PubMed

Chai, Khai Li; Rowan, Gail; Seymour, John F; Burbury, Kate; Carney, Dennis; Tam, Constantine S

2017-12-01

The management of AF represents a major challenge in patients with CLL, especially in elderly patients with multiple comorbidities who are representative of the majority of patients with CLL. This is especially complex in the case of ibrutinib. Many anticoagulants have potential for pharmacological interaction with ibrutinib, and ibrutinib itself has antiplatelet properties. Use of ibrutinib therapy in these patients mandates review and revision of the need for anticoagulation and best anticoagulant to use. Herein, we review the current knowledge of the metabolism of common anticoagulants and how they may interact with ibrutinib.

Severe jaundice due to intrahepatic cholestasis after initiating anticoagulation with rivaroxaban.

PubMed

Aslan, Abdullah N; Sari, Cenk; Baştuğ, Serdal; Sari, Sevil Ö; Akçay, Murat; Durmaz, Tahir; Bozkurt, Engin

2016-03-01

Rivaroxaban, a highly selective direct factor Xa inhibitor, is a new oral anticoagulant approved by the US Food and Drug Administration in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation. Because of its efficacy and once-a-day dosing, it is commonly preferred in patients with nonvalvular atrial fibrillation and intolerance to warfarin in clinical practice. However, it can result in some adverse effects such as bleeding, rashes and liver injury. Here, we described a very rare adverse reaction of rivaroxaban, jaundice due to intrahepatic cholestasis, appeared in a 71-year-old male patient after taking rivaroxaban.

Prevention of thromboembolic events in patients with atrial fibrillation - new anticoagulants.

PubMed

Campos, Alexandre Holthausen; Cirenza, Cláudio

2011-09-01

The authors present alternatives for the treatment of cardiac arrhythmias. Its detection is based on the use of different methods that record the cardiac electrical activity. The treatment involves intervening in the underlying disorder, antiarrhythmic drugs, stimulation and cardiac defibrillation devices, and, less often, surgery. The technological advances in the last two decades have provided greater efficiency in diagnoses and therapy. Atrial fibrilation patients will benefit from a new set of anticoagulant drugs tested in the past three years. The potential advantages include greater safety and efficacy, as well as convenience for not requiring frequent laboratory controls.

Device-identified atrial fibrillation at pacing clinics. Should it guide anticoagulation?

PubMed

Merinopoulos, Ioannis; Raphael, Claire E; Yardley, Alaina; Goonewardene, Manoj; Vassiliou, Vassilios S

2016-03-15

In recent years, there has been a significant increase in the number of devices implanted following improvement in their safety profile, extension of indications and reduction in cost. Although the reason remains largely the beneficial effect on heart rhythm stabilisation, implanted devices might also have additional advantages, notably identification of silent arrhythmia. Should clinicians therefore act on device-identified atrial fibrillation (AF) and should such identification be used to guide anticoagulation management? This review evaluates the current evidence on the management of device-identified asymptomatic AF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[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.

[Oral anticogulation for non-valvular atrial fibrilation in the elderly].

PubMed

Veiga Fernández, Fernando; Malfeito Jiménez, María del Rocío; Barros Cerviño, Sonia María; Magariños Losada, María del Mar

2015-01-01

Anticoagulation in elderly people with non-valvular atrial afibrillation (AF) is a challenge, due to the thromboembolic, as well as the haemorrhagic risks. The correct use of anticoagulants in these patients has shown a higher net clinical benefit when comparing it with a younger population. Non-vitamin K antagonist oral anticoagulants (NOACs) have been compared to oral vitamin K antagonists in several studies that included a sufficient number of elderly people. Favourable results for non-vitamin K antagonist oral anticoagulants were obtained in these studies, making them the preferred treatment for this group of patients. Basing the estimations on indirect comparisons, the ideal anticoagulant and the specific dose for each particular case has been determined. Finally, a new algorithm has been developed that relates these parameters. Geriatric assessment is the key to the indication for an anticoagulation, the type of anticoagulant needed, and also the best way to optimise all the factors for a safe anticoagulation. The arrival of non-vitamin K antagonist oral anticoagulants will enhance the efficient thromboembolic prophylaxis rate in elderly people with AF. This new treatment will remove different controversial prophylaxis, such as antiaggregants. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

Comparative effectiveness of rivaroxaban versus warfarin or dabigatran for the treatment of patients with non-valvular atrial fibrillation.

PubMed

Norby, Faye L; Bengtson, Lindsay G S; Lutsey, Pamela L; Chen, Lin Y; MacLehose, Richard F; Chamberlain, Alanna M; Rapson, Ian; Alonso, Alvaro

2017-09-06

Rivaroxaban is an oral anticoagulant approved in the US for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). We determined the effectiveness and associated risks of rivaroxaban versus other oral anticoagulants in a large real-world population. We selected NVAF patients initiating oral anticoagulant use in 2010-2014 enrolled in MarketScan databases. Rivaroxaban users were matched with warfarin and dabigatran users by age, sex, enrolment date, anticoagulant initiation date, and high-dimensional propensity score. Study endpoints, including ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding, were identified from inpatient diagnostic codes. Multivariable Cox models were used to assess associations between type of anticoagulant and outcomes. The analysis included 44,340 rivaroxaban users matched to 89,400 warfarin and 16,957 dabigatran users (38% female, mean age 70) with 12 months of mean follow-up. Anticoagulant-naïve rivaroxaban initiators, but not those switching from warfarin, had lower risk of ischemic stroke [hazard ratio (HR) (95% confidence interval (CI)): 0.75 (0.62, 0.91)] and ICB [HR (95%CI): 0.55, (0.39, 0.78)] than warfarin users. In contrast, anticoagulant-experienced rivaroxaban initiators had higher risk of GI bleeding than warfarin users [HR (95%CI): 1.55 (1.32, 1.83)]. Endpoint rates were similar when comparing anticoagulant-naïve rivaroxaban and dabigatran initiators, with the exception of higher GI bleeding risk in rivaroxaban users [HR (95%CI) 1.28 (1.06, 1.54)]. There were no significant differences in the risk of MI among the comparison groups. In this large real-world sample of NVAF patients, effectiveness and risks of rivaroxaban versus warfarin differed by prior anticoagulant status, while effectiveness of rivaroxaban versus dabigatran differed in GI bleeding risk.

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study.

PubMed

Wilson, Duncan; Ambler, Gareth; Shakeshaft, Clare; Brown, Martin M; Charidimou, Andreas; Al-Shahi Salman, Rustam; Lip, Gregory Y H; Cohen, Hannah; Banerjee, Gargi; Houlden, Henry; White, Mark J; Yousry, Tarek A; Harkness, Kirsty; Flossmann, Enrico; Smyth, Nigel; Shaw, Louise J; Warburton, Elizabeth; Muir, Keith W; Jäger, Hans Rolf; Werring, David J

2018-06-01

Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0-20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1-5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27-10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29-0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53-0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60-0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07-0·43, p=0·0065; and 0·33, 0·14-0·51, p=0·00059, respectively). In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. The Stroke Association and the British Heart Foundation. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Clinical events after interruption of anticoagulation in patients with atrial fibrillation: An analysis from the ENGAGE AF-TIMI 48 trial.

PubMed

Cavallari, Ilaria; Ruff, Christian T; Nordio, Francesco; Deenadayalu, Naveen; Shi, Minggao; Lanz, Hans; Rutman, Howard; Mercuri, Michele F; Antman, Elliott M; Braunwald, Eugene; Giugliano, Robert P

2018-04-15

Patients with atrial fibrillation (AF) who interrupt anticoagulation are at high risk of thromboembolism and death. Patients enrolled in the ENGAGE AF-TIMI 48 trial (randomized comparison of edoxaban vs. warfarin) who interrupted study anticoagulant for >3 days were identified. Clinical events (ischemic stroke/systemic embolism, major cardiac and cerebrovascular events [MACCE]) were analyzed from day 4 after interruption until day 34 or study drug resumption. During 2.8 years median follow-up, 13,311 (63%) patients interrupted study drug for >3 days. After excluding those who received open-label anticoagulation during the at-risk window, the population for analysis included 9148 patients. The rates of ischemic stroke/systemic embolism and MACCE post interruption were substantially greater than in patients who never interrupted (15.42 vs. 0.26 and 60.82 vs. 0.36 per 100 patient-years, respectively, p adj  < .001). Patients who interrupted study drug for an adverse event (44.1% of the cohort), compared to those who interrupted for other reasons, had an increased risk of MACCE (HR adj 2.75; 95% CI 2.02-3.74, p < .0001), but similar rates of ischemic stroke/systemic embolism. Rates of clinical events after interruption of warfarin and edoxaban were similar. Interruption of study drug was frequent in patients with AF and was associated with a substantial risk of major cardiac and cerebrovascular events over the ensuing 30 days. This risk was particularly high in patients who interrupted as a result of an adverse event; these patients deserve close monitoring and resumption of anticoagulation as soon as it is safe to do so. Copyright © 2018 Elsevier B.V. All rights reserved.

[Patients' characteristics and clinical management of atrial fibrillation in primary healthcare in Spain: FIATE Study].

PubMed

Lobos-Bejarano, José María; del Castillo-Rodríguez, José Carlos; Mena-González, Amparo; Alemán-Sánchez, José J; Cabrera de León, Antonio; Barón-Esquivias, Gonzalo; Pastor-Fuentes, Agustín

2013-10-05

The main therapeutic objective in atrial fibrillation (AF) patients is stroke prevention. This study is aimed to determine whether the anticoagulant therapy may be appropriate regarding to the Guidelines and patients' profile in primary healthcare in Spain. A national, multicenter, cross-sectional study of AF patients attended in primary healthcare in Spain has been conducted. The study involved 185 family physicians whose patients were randomized. A total of 3,759 AF patients were randomized from the clinical records, and 2,070 were included in the study, at an average age of 74 (11) years old (50.7% female). Most of them (78%) had permanent AF and high comorbidity rates (hypertension 75%, obesity 30%, diabetes 27%, heart failure 20%, coronary heart disease 17%, and social risk 15%). Patients diagnosed in primary healthcare were more frequently asymptomatic than in hospital setting (36%; P<.001). The therapeutic strategy was based on the heart rate control in 4 out of 5 patients. Anticoagulation therapy was widely used (84%), more frequently in patients with permanent vs. non-permanent AF (91 vs. 60%, P<.001). Follow-up and monitoring was mainly performed in primary care (72%). The anticoagulation control was suboptimal, with a 66% of the international normalized ratio (INR) in therapeutic range, dropping to 33% when the last 3 available INR were included (P<.001). A high rate of patients with anticoagulant therapy in primary healthcare has been found in this research. INR control, however, remains suboptimal. Heart rate control is the most commonly used strategy. The decision about the anticoagulation should be based on the thromboembolic risk rather than in the arrhytmia type. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Aspirin in stroke prevention in nonvalvular atrial fibrillation and stable vascular disease: an era of new anticoagulants.

PubMed

Turagam, Mohit K; Velagapudi, Poonam; Leal, Miguel A; Kocheril, Abraham G

2012-04-01

Atrial fibrillation (AF) is a major cause of ischemic stroke, especially in the elderly. There are currently enough data to support the notion that anticoagulation with warfarin or dabigatran is far superior to aspirin in the prevention of stroke or systemic embolism in AF. Aspirin is the preferred modality in patients who are either not candidates for anticoagulation, such as patients with increased risk for bleeding, low-risk patients based on the CHADS2 score or patients who have difficulty in maintaining a therapeutic international normalized ratio. There is no dispute on the recommendations regarding stroke prevention in high-risk patients (CHADS2 risk score of 2 and beyond) with AF. However, there is some controversy regarding the appropriate strategy (anticoagulation vs aspirin) for stroke prevention in low-risk patients (CHA2DS2-VASc score of 0-1). Novel oral anticoagulant drugs (direct thrombin inhibitors and Factor Xa inhibitors) might further diminish the role of aspirin for stroke prevention in AF due to their superior efficacy, lack of need for monitoring of therapeutic effects and lower bleeding risk when compared with warfarin, especially in patients with stable vascular disease.

Impact of a Computerized Antithrombotic Risk Assessment Tool on the Prescription of Thromboprophylaxis in Atrial Fibrillation: Hospital Setting.

PubMed

Pandya, E; Masood, N; Wang, Y; Krass, I; Bajorek, B

2018-01-01

The computerized antithrombotic risk assessment tool (CARAT) is an online decision-support algorithm that facilitates a systematic review of a patient's stroke risk, bleeding risk, and pertinent medication safety considerations, to generate an individualized treatment recommendation. The CARAT was prospectively applied across 2 hospitals in the greater Sydney area. Its impact on antithrombotics utilization for thromboprophylaxis in patients with nonvalvular atrial fibrillation was evaluated. Factors influencing prescribers' treatment selection were identified. The CARAT recommended a change in baseline therapy for 51.8% of patients. Among anticoagulant-eligible patients (ie, where the risk of stroke outweighed the risk of bleeding) using "nil therapy" or antiplatelet therapy at baseline, the CARAT recommended an upgrade to warfarin in 60 (30.8%) patients. For those in whom the bleeding risk outweighed the stroke risk, the CARAT recommended a downgrade from warfarin to safer alternatives (eg, aspirin) in 37 (19%) patients. Among the "most eligible" (ie, high stroke risk, low bleeding risk, no contraindications; n = 75), the CARAT recommended warfarin for all cases. Discharge therapy observed a marginal increase in anticoagulation prescription in eligible patients (n = 116; 57.8% vs 64.7%, P = .35) compared to baseline. Predictors of warfarin use (vs antiplatelets) included congestive cardiac failure, diabetes mellitus, and polypharmacy. The CARAT was able to optimize the selection of therapy, increasing anticoagulant use among eligible patients. With the increasing complexity of decision-making, such tools may be useful adjuncts in therapy selection in atrial fibrillation. Future studies should explore the utility of such tools in selecting therapies from within an expanded treatment armamentarium comprising the non-vitamin K antagonist oral anticoagulants.

Status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. REACT-AF Study.

PubMed

de Andrés-Nogales, F; Oyagüez, I; Betegón-Nicolás, L; Canal-Fontcuberta, C; Soto-Álvarez, J

2015-03-01

Oral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. The Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: a) persistence of oral anticoagulant treatment (time to discontinuation); b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; c) therapeutic compliance (medication possession ratio); d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. The patients treated with oral anticoagulants (n=7,526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. Forty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Aversion to ambiguity and willingness to take risks affect therapeutic decisions in managing atrial fibrillation for stroke prevention: results of a pilot study in family physicians.

PubMed

Raptis, Stavroula; Chen, Jia Ning; Saposnik, Florencia; Pelyavskyy, Roman; Liuni, Andrew; Saposnik, Gustavo

2017-01-01

Anticoagulation is the therapeutic paradigm for stroke prevention in patients with atrial fibrillation (AF). It is unknown how physicians make treatment decisions in primary stroke prevention for patients with AF. To evaluate the association between family physicians' risk preferences (aversion risk and ambiguity) and therapeutic recommendations (anticoagulation) in the management of AF for primary stroke prevention by applying concepts from behavioral economics. Overall, 73 family physicians participated and completed the study. Our study comprised seven simulated case vignettes, three behavioral experiments, and two validated surveys. Behavioral experiments and surveys incorporated an economic framework to determine risk preferences and biases (e.g., ambiguity aversion, willingness to take risks). The primary outcome was making the correct decision of anticoagulation therapy. Secondary outcomes included medical errors in the management of AF for stroke prevention. Overall, 23.3% (17/73) of the family physicians elected not to escalate the therapy from antiplatelets to anticoagulation when recommended by best practice guidelines. A total of 67.1% of physicians selected the correct therapeutic options in two or more of the three simulated case vignettes. Multivariate analysis showed that aversion to ambiguity was associated with appropriate change to anticoagulation therapy in the management of AF (OR 5.48, 95% CI 1.08-27.85). Physicians' willingness to take individual risk in multiple domains was associated with lower errors (OR 0.16, 95% CI 0.03-0.86). Physicians' aversion to ambiguity and willingness to take risks are associated with appropriate therapeutic decisions in the management of AF for primary stroke prevention. Further large scale studies are needed.

Aversion to ambiguity and willingness to take risks affect therapeutic decisions in managing atrial fibrillation for stroke prevention: results of a pilot study in family physicians

PubMed Central

Saposnik, Florencia; Pelyavskyy, Roman; Liuni, Andrew; Saposnik, Gustavo

2017-01-01

Background Anticoagulation is the therapeutic paradigm for stroke prevention in patients with atrial fibrillation (AF). It is unknown how physicians make treatment decisions in primary stroke prevention for patients with AF. Objectives To evaluate the association between family physicians’ risk preferences (aversion risk and ambiguity) and therapeutic recommendations (anticoagulation) in the management of AF for primary stroke prevention by applying concepts from behavioral economics. Methods Overall, 73 family physicians participated and completed the study. Our study comprised seven simulated case vignettes, three behavioral experiments, and two validated surveys. Behavioral experiments and surveys incorporated an economic framework to determine risk preferences and biases (e.g., ambiguity aversion, willingness to take risks). The primary outcome was making the correct decision of anticoagulation therapy. Secondary outcomes included medical errors in the management of AF for stroke prevention. Results Overall, 23.3% (17/73) of the family physicians elected not to escalate the therapy from antiplatelets to anticoagulation when recommended by best practice guidelines. A total of 67.1% of physicians selected the correct therapeutic options in two or more of the three simulated case vignettes. Multivariate analysis showed that aversion to ambiguity was associated with appropriate change to anticoagulation therapy in the management of AF (OR 5.48, 95% CI 1.08–27.85). Physicians’ willingness to take individual risk in multiple domains was associated with lower errors (OR 0.16, 95% CI 0.03–0.86). Conclusion Physicians’ aversion to ambiguity and willingness to take risks are associated with appropriate therapeutic decisions in the management of AF for primary stroke prevention. Further large scale studies are needed. PMID:28979101

Risk of long-term anticoagulation under sustained severe arterial hypertension: A translational study comparing warfarin and the new oral anticoagulant apixaban

PubMed Central

Pfeilschifter, Waltraud; Steinstraesser, Thurid; Paulus, Patrick; Zeiner, Pia Susan; Bohmann, Ferdinand; Theisen, Alf; Lindhoff-Last, Edelgard; Penski, Cornelia; Wagner, Marlies; Mittelbronn, Michel

2016-01-01

New oral anticoagulants for the prevention of stroke and systemic embolism in patients with atrial fibrillation have recently been introduced. In this translational study, we explored the risk of long-term anticoagulation on intracerebral hemorrhage under sustained severe arterial hypertension. We initiated anticoagulation with warfarin or apixaban in spontaneously hypertensive rats prone to develop severe hypertension and subsequent intracerebral bleeding complications. A non-anticoagulated group served as control. During an 11-week-study period, blood pressure, anticoagulation parameters, and clinical status were determined regularly. The incidence of histopathologically proven intracerebral hemorrhage was defined as the primary endpoint. Both warfarin and apixaban anticoagulation was fairly stable during the study period, and all rats developed severe hypertension. Intracerebral hemorrhage was determined in 29% (4/14) of warfarin rats and in 10% (1/10) of apixaban rats. Controls did not show cerebral bleeding complications (chi-square not significant). Mortality rate at study termination was 33% (2/6) in controls, 43% (6/14) in the warfarin group, and 60% (6/10) in the apixaban group. Animals died from extracerebral complications in most cases. Our study describes an experimental intracerebral hemorrhage model in the context of sustained hypertension and long-term anticoagulation. Extracerebral bleeding complications occurred more often in warfarin-treated animals compared with apixaban and control rats. PMID:27189904

Management of recent-onset sustained atrial fibrillation: pharmacologic and nonpharmacologic strategies.

PubMed

Lau, Dennis H; Kalman, Jonathan; Sanders, Prashanthan

2014-09-01

Recent studies have highlighted significant variations in the management of recent-onset sustained atrial fibrillation (AF). We aim to provide a succinct and clear management algorithm for physicians treating patients with recent-onset sustained AF. We performed a comprehensive search of the literature on the management of recent-onset sustained AF with focus on studies reporting cardioversion of AF, antiarrhythmic agents, and anticoagulation. We also reviewed recent practice guidelines on AF management. This review provides a guide on a tailored management approach of patients with recent-onset sustained AF. After initial detailed clinical assessment, optimal rate and rhythm control options can be provided, depending on hemodynamic stability, duration of AF episode, and AF stroke risk. Issues surrounding electrical and pharmacologic cardioversion are discussed in detail. We emphasize the importance of thromboembolic risk assessment and appropriate anticoagulation surrounding the point of cardioversion. Last, we highlighted the need for appropriate specialized follow-up care after acute AF management. Despite the highly heterogeneous clinical presentations, management of recent-onset sustained AF must include stroke risk assessment, appropriate anticoagulation, and follow-up care in all patients beyond optimum rate and rhythm control strategies. Copyright © 2014. Published by Elsevier Inc.

[Stroke prevention in atrial fibrillation in Germany. Situational analysis of treatment reality based on retrospective data].

PubMed

Mergenthaler, Ulrike; Kostev, Karel; Moosmang, Sven; Thate-Waschke, Inga-Marion; Haas, Sylvia

2017-12-01

Guideline-based, risk-adjusted therapy with anticoagulants reduce thromboembolic stroke risk in patients with atrial fibrillation (AF). This study analyzed use of oral anticoagulation in German AF-patients. Access to anonymized patient records was made via IMS Health Disease Analyzer database (sample size: 113,619 patients with ICD-10 Code I48.-; observation period: 11/2010-10/2013). Results were subsequently extrapolated to all general practitioners' (GPs) and cardiological practices in Germany. In 2011 12-month AF-prevalence was extrapolated to 2.1 million patients (first diagnosed: n = 537.548). In 2012 AF-prevalence gone up to 2.2 million cases (first diagnosed: n = 537.548) and in 2013 to 2.8 million (first diagnosed: n = 636.571). Commonly prescribed oral anticoagulants (OAC) were vitamin K antagonists (VKA). Unstable INR setting, private health insurance, hospital admission, heart failure or hypertension increased probability of change from VKA to non-vitamin K antagonist oral anticoagulants (NOAC). 17.3-36.5% of patients with CHA 2 DS 2 -VASc-score ≥ 2 did not receive any thromboembolism prophylaxis; 38.5% with CHA 2 DS 2 -VASc-score = 0 received unnecessarily OACs. For 2013 a potential of 29.749 ischemic strokes in GP practices was calculated, which possibly can be avoided by thromboembolism prophylaxis according to guidelines. Risk-based anticoagulation showed requirements for optimization. Use of OACs, according to guideline recommendations, would minimize bleeding risks, reduce ischemic strokes and could release resources.

Triple vs Dual Antithrombotic Therapy in Patients with Atrial Fibrillation and Coronary Artery Disease.

PubMed

Lopes, Renato D; Rao, Meena; Simon, DaJuanicia N; Thomas, Laine; Ansell, Jack; Fonarow, Gregg C; Gersh, Bernard J; Go, Alan S; Hylek, Elaine M; Kowey, Peter; Piccini, Jonathan P; Singer, Daniel E; Chang, Paul; Peterson, Eric D; Mahaffey, Kenneth W

2016-06-01

The role of triple antithrombotic therapy vs dual antithrombotic therapy in patients with both atrial fibrillation and coronary artery disease remains unclear. This study explores the differences in treatment practices and outcomes between triple antithrombotic therapy and dual antithrombotic therapy in patients with atrial fibrillation and coronary artery disease. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (n = 10,135), we analyzed outcomes in patients with coronary artery disease (n = 1827) according to treatment with triple antithrombotic therapy (defined as concurrent therapy with an oral anticoagulant, a thienopyridine, and aspirin) or dual antithrombotic therapy (comprising either an oral anticoagulant and one antiplatelet agent [OAC plus AA] or 2 antiplatelet drugs and no anticoagulant [DAP]). The use of triple antithrombotic therapy, OAC plus AA, and DAP at baseline was 8.5% (n = 155), 80.4% (n = 1468), and 11.2% (n = 204), respectively. Among patients treated with OAC plus AA, aspirin was the most common antiplatelet agent used (90%), followed by clopidogrel (10%) and prasugrel (0.1%). The use of triple antithrombotic therapy was not affected by patient risk of either stroke or bleeding. Patients treated with triple antithrombotic therapy at baseline were hospitalized for all causes (including cardiovascular) more often than patients on OAC plus AA (adjusted hazard ratio 1.75; 95% confidence interval, 1.35-2.26; P <.0001) or DAP (hazard ratio 1.82; 95% confidence interval, 1.25-2.65; P = .0018). Rates of major bleeding or a combined cardiovascular outcome were not significantly different by treatment group. Choice of antithrombotic therapy in patients with atrial fibrillation and coronary artery disease was not affected by patient stroke or bleeding risks. Triple antithrombotic therapy-treated patients were more likely to be hospitalized for all causes than those on OAC plus AA or on DAP. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Optimizing the use of oral anticoagulant therapy for atrial fibrilation in primary care: a pharmacist-led intervention.

PubMed

Virdee, Mandeep S; Stewart, Derek

2017-02-01

Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA 2 DS 2 -VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA 2 DS 2 -VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist-led intervention re-aligned oral anticoagulant therapy to the latest evidence based guidelines for stroke prophylaxis, whilst simultaneously correcting the over-utilisation of antiplatelet therapy.

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.

Cost-effectiveness of pharmacogenetics-guided warfarin therapy vs. alternative anticoagulation in atrial fibrillation.

PubMed

Pink, J; Pirmohamed, M; Lane, S; Hughes, D A

2014-02-01

Pharmacogenetics-guided warfarin dosing is an alternative to standard clinical algorithms and new oral anticoagulants for patients with nonvalvular atrial fibrillation. However, clinical evidence for pharmacogenetics-guided warfarin dosing is limited to intermediary outcomes, and consequently, there is a lack of information on the cost-effectiveness of anticoagulation treatment options. A clinical trial simulation of S-warfarin was used to predict times within therapeutic range for different dosing algorithms. Relative risks of clinical events, obtained from a meta-analysis of trials linking times within therapeutic range with outcomes, served as inputs to an economic analysis. Neither dabigatran nor rivaroxaban were cost-effective options. Along the cost-effectiveness frontier, in relation to clinically dosed warfarin, pharmacogenetics-guided warfarin and apixaban had incremental cost-effectiveness ratios of £13,226 and £20,671 per quality-adjusted life year gained, respectively. On the basis of our simulations, apixaban appears to be the most cost-effective treatment.

Stroke prevention with oral anticoagulation in older people with atrial fibrillation - a pragmatic approach.

PubMed

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-08-01

With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians' fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients' views.

Stroke Prevention with Oral Anticoagulation in Older People with Atrial Fibrillation - A Pragmatic Approach

PubMed Central

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-01-01

With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians’ fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients’ views. PMID:23185715

Prevalence of stroke and the need for thromboprophylaxis in young patients with atrial fibrillation: a cohort study.

PubMed

Lin, Andrew H; Oakley, Luke S; Phan, Hoanganh L; Shutt, Brennan J; Birgersdotter-Green, Ulrika; Francisco, Gregory M

2014-03-01

Atrial fibrillation is the most common cardiac arrhythmia, and age is a well-established independent risk factor for stroke in these patients. Whereas high-risk patients clearly benefit from anticoagulation to prevent stroke, less is known about how to treat low-risk patients. Despite the recent guidelines and studies demonstrating no benefit and excess bleeding risk with aspirin, many low-risk patients still receive this medication. Our objective was to determine the stroke rate in young patients with atrial fibrillation, a group of previously unstudied and predominantly low-risk patients. We hypothesized that the event rate would be so low as to preclude benefit from antithrombotic medications. A retrospective chart review identified patients with atrial fibrillation between the age of 18 and 35. Exclusion criteria included no ECG documentation of atrial fibrillation, anticoagulation, except around the time of cardioversion, and surgical valve disease. The primary outcome was stroke during the period of observation. The final cohort included 99 patients, mean age 27.6 years, followed for a mean of 4.3 years. Mean CHADS2 and CHA2DS2-VASc scores were 0.26 and 0.4, respectively. A total of 42.4% were taking aspirin for over 50% of the time. There was one event identified, a transient ischemic attack in a man not on aspirin with CHADS2 and CHADS2-VASc scores of 1, resulting in event rates of 0.234 per 100 patient-years overall or 0.392 among those not on aspirin. Patients with nonvalvular atrial fibrillation under age 35 have an exceedingly low stroke risk. We assert that aspirin may be unnecessary for most patients in this population, especially those with a CHA2DS2-VASc score of 0.

Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in Newly Diagnosed Atrial Fibrillation.

PubMed

Williams, Brent A; Evans, Michael A; Honushefsky, Ashley M; Berger, Peter B

2017-10-12

Though warfarin has historically been the primary oral anticoagulant for stroke prevention in newly diagnosed atrial fibrillation (AF), several new direct oral anticoagulants may be preferred when anticoagulation control with warfarin is expected to be poor. This study developed a prediction model for time in therapeutic range (TTR) among newly diagnosed AF patients on newly initiated warfarin as a tool to assist decision making between warfarin and direct oral anticoagulants. This electronic medical record-based, retrospective study included newly diagnosed, nonvalvular AF patients with no recent warfarin exposure receiving primary care services through a large healthcare system in rural Pennsylvania. TTR was estimated as the percentage of time international normalized ratio measurements were between 2.0 and 3.0 during the first year following warfarin initiation. Candidate predictors of TTR were chosen from data elements collected during usual clinical care. A TTR prediction model was developed and temporally validated and its predictive performance was compared with the SAMe-TT 2 R 2 score (sex, age, medical history, treatment, tobacco, race) using R 2 and c-statistics. A total of 7877 newly diagnosed AF patients met study inclusion criteria. Median (interquartile range) TTR within the first year of starting warfarin was 51% (32, 67). Of 85 candidate predictors evaluated, 15 were included in the final validated model with an R 2 of 15.4%. The proposed model showed better predictive performance than the SAMe-TT 2 R 2 score ( R 2 =3.0%). The proposed prediction model may assist decision making on the proper mode of oral anticoagulant among newly diagnosed AF patients. However, predicting TTR on warfarin remains challenging. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials.

PubMed

Flaker, Greg C; Gruber, Michael; Connolly, Stuart J; Goldman, Steven; Chaparro, Sandra; Vahanian, Alec; Halinen, Matti O; Horrow, Jay; Halperin, Jonathan L

2006-11-01

Aspirin is used in combination with anticoagulant therapy in patients with atrial fibrillation (AF), but evidence of additional efficacy is not available. We compared ischemic events and bleeding in the SPORTIF III and IV randomized trials of anticoagulation with warfarin (international normalized ratio 2-3) or fixed-dose ximelagatran. Low-dose aspirin (<100 mg/d) was allowed based on prevailing guidelines. The 14% of patients receiving aspirin more often had diabetes (27.5% vs 23%, P < .01), coronary artery disease (69% vs 41%, P < .01), previous stroke or transient ischemic attack (26% vs 20%, P < .01), and left ventricular dysfunction (41% vs 36%, P < .01). Addition of aspirin to either warfarin or ximelagatran was associated with no reduction in stroke or systemic embolism. Major bleeding occurred significantly more often with aspirin plus warfarin (3.9% per year) than with warfarin alone (2.3% per year, P < .01), aspirin plus ximelagatran (2.0% per year), or ximelagatran alone (1.9% per year). The rate of myocardial infarction with aspirin and warfarin (0.6% per year) was not significantly different from that with ximelagatran alone (1.0% per year), warfarin alone (1.0% per year), or aspirin and ximelagatran (1.4% per year). Aspirin combined with anticoagulant therapy was associated with no reduction in stroke, systemic embolism, or myocardial infarction in patients with AF. Aspirin combined with warfarin was associated with an incremental rate of major bleeding of 1.6% per year. No increased major bleeding occurred with aspirin and ximelagatran. These results suggest that the risks associated with addition of aspirin to anticoagulation in patients with AF outweigh the benefit.

Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial.

PubMed

Pol, Tymon; Held, Claes; Westerbergh, Johan; Lindbäck, Johan; Alexander, John H; Alings, Marco; Erol, Cetin; Goto, Shinya; Halvorsen, Sigrun; Huber, Kurt; Hanna, Michael; Lopes, Renato D; Ruzyllo, Witold; Granger, Christopher B; Hijazi, Ziad

2018-02-01

Dyslipidemia is a major risk factor for cardiovascular events. The prognostic importance of lipoproteins in patients with atrial fibrillation is not well understood. We aimed to explore the association between apolipoprotein A1 (ApoA1) and B (ApoB) and cardiovascular events in patients with atrial fibrillation receiving oral anticoagulation. Using data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, ApoA1 and ApoB plasma levels were measured at baseline in 14 884 atrial fibrillation patients. Median length of follow-up was 1.9 years. Relationships between continuous levels of ApoA1 and ApoB and clinical outcomes were evaluated using Cox models adjusted for cardiovascular risk factors, medication including statins, and cardiovascular biomarkers. A composite ischemic outcome (ischemic stroke, systemic embolism, myocardial infarction, and cardiovascular death) was used as the primary end point. Median (25th, 75th) ApoA1 and ApoB levels were 1.10 (0.93, 1.30) and 0.70 g/L (0.55, 0.85), respectively. In adjusted analyses, higher levels of ApoA1 were independently associated with a lower risk of the composite ischemic outcome (hazard ratio, 0.81; P <0.0001). Similar results were observed for the individual components of the composite outcome. ApoB was not significantly associated with the composite ischemic outcome ( P =0.8240). Neither apolipoprotein was significantly associated with major bleeding. There was no interaction between lipoproteins and randomized treatment for the primary outcome (both P values ≥0.2448). In patients with atrial fibrillation on oral anticoagulation, higher levels of ApoA1 were independently associated with lower risk of ischemic cardiovascular outcomes. Investigating therapies targeting dyslipidemia may thus be useful to improve cardiovascular outcomes in patients with atrial fibrillation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2018 The Authors and Bristol‐Myers Squibb. Published on behalf of the American Heart Association, Inc., by Wiley.

Venous hemostasis postcatheter ablation of atrial fibrillation while under therapeutic levels of oral and intravenous anticoagulation.

PubMed

Issa, Ziad F; Amr, Bashar S

2015-11-01

Catheter ablation of atrial fibrillation (AF) requires utilizing multiple venous femoral sheaths in conjunction with aggressive periprocedural anticoagulation, which can lead to increased risk of vascular access complications. The objective of this study is to evaluate the safety and efficacy of the "figure-of-eight" ("F-8") suture technique for femoral venous hemostasis while on therapeutic doses of intravenous anticoagulation at the time of sheath removal. In this case-control analysis, 376 consecutive patients underwent AF ablation while on uninterrupted oral anticoagulation and received intraprocedural heparin. In the first 253 patients (the control group), manual pressure was used for femoral venous hemostasis after reversal of heparin effects. The subsequent 123 patients (the F-8 group) had femoral venous hemostasis using the F-8 suture technique and while under therapeutic heparin effects. The F-8 subcutaneous suture technique achieved adequate venous hemostasis in 98.4% of patients. As compared to the control group, there was significantly less frequent utilization of the FemoStop compression assist device (1.2 vs. 16.8%, p < 0.0001) and in a significantly shorter interval (6.8 ± 5.7 vs. 50.7 ± 12.2 min, p < 0.0001). Vascular access complications and thromboembolic events occurred in 9.8% in the F-8 group vs. 13.0% in the control group (p = 0.678). Immediate hemostasis of the femoral venous access sites after insertion of multiple sheaths for AF ablation in the presence of anticoagulation can be safely and effectively achieved using the F-8 suture technique. This technique helps minimize the period of inadequate anticoagulation immediately following ablation and shortens the time required to achieve adequate hemostasis.

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.

Cost-effectiveness of dabigatran for stroke prevention in atrial fibrillation in Switzerland.

PubMed

Pletscher, Mark; Plessow, Rafael; Eichler, Klaus; Wieser, Simon

2013-01-08

Atrial fibrillation is a major risk factor for ischemic stroke and anticoagulation therapy is indicated to reduce risk. Dabigatran is a new oral anticoagulant that does not require INR monitoring. This study evaluated the cost-effectiveness of dabigatran versus vitamin K antagonists for stroke prevention in atrial fibrillation in Switzerland. A Markov model simulating the course of treatment and occurrence of clinical events in two treatment arms over the lifetime of patients was adapted to the Swiss context. The adaptation included the cost of anticoagulation therapy and clinical events in Switzerland. The cost of inpatient care was estimated on data of all inpatient hospital stays in 2008. The calculation of outpatient care costs was based on peer reviewed studies, expert interviews and local tariffs. Patients treated with dabigatran had a higher life expectancy and experienced more quality adjusted life years (QALY) while incurring higher costs than patients treated with vitamin K antagonists. The estimated incremental cost-effectiveness ratio (ICER) was CHF 25,108.‒ per QALY with 110 mg and CHF 9,702 per QALY with 150 mg of dabigatran. A sequential dosage scheme, in which 150 mg are administered up to the age of 80 years and 110 mg thereafter, resulted in an ICER of CHF 10,215 per QALY. A sensitivity analysis confirmed that these results are robust. Dabigatran can be considered cost-effective in comparison with vitamin K antagonists in the Swiss context. The higher drug cost of dabigatran is compensated by savings in INR monitoring, lower cost of clinical events and QALY-gains.

The Influence of Socioeconomic Status on Selection of Anticoagulation for Atrial Fibrillation.

PubMed

Sholzberg, Michelle; Gomes, Tara; Juurlink, David N; Yao, Zhan; Mamdani, Muhammad M; Laupacis, Andreas

2016-01-01

Without third-party insurance, access to marketed drugs is limited to those who can afford to pay. We examined this phenomenon in the context of anticoagulation for patients with nonvalvular atrial fibrillation (NVAF). To determine whether, among older Ontarians receiving anticoagulation for NVAF, patients of higher socioeconomic status (SES) were more likely to switch from warfarin to dabigatran prior to its addition to the provincial formulary. Population-based retrospective cohort study of Ontarians aged 66 years and older, between 2008 and 2012. Socioeconomic status, as approximated by median neighborhood income. We identified two groups of older adults with nonvalvular atrial fibrillation: those who appeared to switch from warfarin to dabigatran after its market approval but prior to its inclusion on the provincial formulary ("switchers"), and those with ongoing warfarin use during the same interval ("non-switchers"). We studied 34,797 patients, including 3183 "switchers" and 31,614 "non-switchers". We found that higher SES was associated with switching to dabigatran prior to its coverage on the provincial formulary (p<0.0001). In multivariable analysis, subjects in the highest quintile were 50% more likely to switch to dabigatran than those in the lowest income quintile (11.3% vs. 7.3%; adjusted odds ratio 1.50; 95% CI 1.32 to 1.68). Following dabigatran's addition to the formulary, the income gradient disappeared. We documented socioeconomic inequality in access to dabigatran among patients receiving warfarin for NVAF. This disparity was eliminated following the drug's addition to the provincial formulary, highlighting the importance of timely reimbursement decisions.

Anticoagulant use for prevention of stroke in a commercial population with atrial fibrillation.

PubMed

Patel, Aarti A; Lennert, Barb; Macomson, Brian; Nelson, Winnie W; Owens, Gary M; Mody, Samir H; Schein, Jeff

2012-07-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and patients with AF are at an increased risk for stroke. Thromboprophylaxis with vitamin K antagonists reduces the annual incidence of stroke by approximately 60%, but appropriate thromboprophylaxis is prescribed for only approximately 50% of eligible patients. Health plans may help to improve quality of care for patients with AF by analyzing claims data for care improvement opportunities. To analyze pharmacy and medical claims data from a large integrated commercial database to determine the risk for stroke and the appropriateness of anticoagulant use based on guideline recommendations for patients with AF. This descriptive, retrospective claims data analysis used the Anticoagulant Quality Improvement Analyzer software, which was designed to analyze health plan data. The data for this study were obtained from a 10% randomly selected sample from the PharMetrics Integrated Database. This 10% sample resulted in almost 26,000 patients with AF who met the inclusion criteria for this study. Patients with a new or existing diagnosis of AF between July 2008 and June 2010 who were aged ≥18 years were included in this analysis. The follow-up period was 1 year. Demographics, stroke risk level (CHADS2 and CHA2DS2-VASc scores), anticoagulant use, and inpatient stroke hospitalizations were analyzed through the analyzer software. Of the 25,710 patients with AF (CHADS2 score 0-6) who were eligible to be included in this study, 9093 (35%) received vitamin K antagonists and 16,617 (65%) did not receive any anticoagulant. Of the patients at high risk for stroke, as predicted by CHADS2, 39% received an anticoagulant medication. The rates of patients receiving anticoagulant medication varied by age-group-16% of patients aged <65 years, 22% of those aged 65 to 74 years, and 61% of elderly ≥75 years. Among patients hospitalized for stroke, only 28% were treated with an anticoagulant agent in the outpatient setting before admission. Our findings support the current literature, indicating that many patients with AF are not receiving appropriate thromboprophylaxis to counter their risk for stroke. Increased use of appropriate anticoagulation, particularly in high-risk patients, has the potential to reduce the incidence of stroke along with associated fatalities and morbidities.

Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Atrial Fibrillation.

PubMed

Cha, Myung-Jin; Choi, Eue-Keun; Han, Kyung-Do; Lee, So-Ryoung; Lim, Woo-Hyun; Oh, Seil; Lip, Gregory Y H

2017-11-01

There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients. Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA 2 DS 2 -VASc score ≥2) between 2014 and 2015. NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant-naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH. In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban. © 2017 American Heart Association, Inc.

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.

Acute management of bleeding in patients on novel oral anticoagulants.

PubMed

Siegal, Deborah M; Crowther, Mark A

2013-02-01

Novel oral anticoagulants that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are currently available for prevention of venous thromboembolism (VTE) after orthopaedic surgery, treatment of acute VTE, and prevention of arterial thromboembolism in non-valvular atrial fibrillation. These agents offer advantages over VKAs, including rapid onset, shorter half-lives, fewer drug interactions, and lack of need for routine monitoring. However, there are no established agents to reverse their anticoagulant effect. We review the risk of bleeding with the novel oral anticoagulants and the limitations of conventional coagulation assays for measuring anticoagulant effect. We provide an approach to the management of patients with bleeding complications with evidence for various interventions for reversal, where available.

Cardioembolic Stroke.

PubMed

O'Carroll, Cumara B; Barrett, Kevin M

2017-02-01

Cardioembolic stroke is common and disproportionately more disabling than nonembolic mechanisms of stroke. Its incidence is expected to rise because of the age-related incidence of atrial fibrillation and an aging population. This article summarizes the different causes of cardioembolism and outlines current management guidelines. Since cardioembolic stroke is not a single disease entity, its diagnosis requires initial clinical suspicion and a comprehensive evaluation, including ECG, echocardiography, brain imaging, and cardiac monitoring. Atrial fibrillation is the most common cause of cardioembolic stroke, and anticoagulation is usually recommended. This article reviews risk stratification models to assist in the decision-making process and highlights the increased use of novel oral anticoagulants for stroke prevention in atrial fibrillation. New data support the importance of prolonged cardiac monitoring for diagnosing occult atrial fibrillation. Current data on other mechanisms of cardioembolic stroke, such as prosthetic heart valves and aortic arch atherosclerosis, are also presented, and the available evidence regarding patent foramen ovale closure in cryptogenic stroke is summarized. Cardioembolism is an important cause of ischemic stroke, with diverse underlying mechanisms requiring a tailored approach to diagnosis, management, and prevention.

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.

Use of oral anticoagulants in African-American and Caucasian patients with atrial fibrillation: is there a treatment disparity?

PubMed Central

Akinboboye, Olakunle

2015-01-01

Atrial fibrillation (AF) is a very common cardiac arrhythmia, and its prevalence is increasing along with aging in the developed world. This review discusses racial differences in the epidemiology and treatment of AF between African-American and Caucasian patients. Additionally, the effect of race on warfarin and novel oral anticoagulant use is discussed, as well as the role that physicians and patients play in achieving optimal treatment outcomes. Despite having a lower prevalence of AF compared with Caucasians, African-Americans suffer disproportionately from stroke and its sequelae. The possible reasons for this paradox include poorer access to health care, lower health literacy, and a higher prevalence of other stroke-risk factors among African-Americans. Consequently, it is important for providers to evaluate the effects of race, health literacy, access to health care, and cultural barriers on the use of anticoagulation in the management of AF. Warfarin-dose requirements vary across racial groups, with African-American patients requiring a higher dose than Caucasians to maintain a therapeutic international normalized ratio; the novel oral anticoagulants (dabigatran, rivaroxaban, and apixaban) seem to differ in this regard, although data are currently limited. Minority racial groups are not proportionally represented in either real-world studies or clinical trials, but as more information becomes available and other social issues are addressed, the treatment disparities between African-American and Caucasian patients should decrease. PMID:26056467

Clinical characteristics and management of patients with atrial fibrillation treated with direct oral anticoagulants according to blood pressure control.

PubMed

de la Figuera, M; Cinza, S; Egocheaga, I; Marín, N; Prieto, M A

2018-02-14

To determine the clinical characteristics and management of hypertensive patients with nonvalvular atrial fibrillation (AF) treated with direct oral anticoagulants (DOACs) according to blood pressure (BP) control. For this purpose, data from two observational, cross-sectional and multicenter studies were combined. In both studies, patients on chronic treatment with anticoagulants and that were on current treatment with DOACs at least for 3 months were included. Adequate BP was defined as a systolic BP<140mmHg and a diastolic BP<90mmHg (<140/85mmHg if diabetes). Overall, 1036 patients were included. Of these, 881 (85%) had hypertension that were finally analyzed. The presence of other risk factors and cardiovascular disease was common. Mean BP was 132.6±14.3/75.2±9.2mmHg and 70.5% of patients achieved BP goals. Those patients with a poor BP control had more frequently diabetes, and a history of prior labile INR. Patients had a high thromboembolic risk, but without significant differences according to BP control. By contrast, more patients with a poor BP control had a higher bleeding risk (HAS-BLED ≥3: 24.0% vs 35.4%; P<0.001). HAS-BLED score was an independent predictor of poor BP control (odds ratio 1.435; 95% confidence interval 1.216-1.693; P<0.001). Satisfaction with anticoagulant treatment was independent of BP control. More than two thirds of our patients with hypertension and AF anticoagulated with DOACs achieve BP targets, what is clearly superior to that reported in the general hypertensive population. Copyright © 2018 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Start or STop Anticoagulants Randomised Trial (SoSTART)

ClinicalTrials.gov

2018-06-26

Intracranial Hemorrhages; Intracranial Hemorrhage, Hypertensive; Subarachnoid Hemorrhage; Subdural Hematoma; Intraventricular Hemorrhage; Atrial Fibrillation; Atrial Flutter; Small Vessel Cerebrovascular Disease; Microhaemorrhage

Cardiac arrest due to left circumflex coronary artery embolism as a complication of subtherapeutic oral anticoagulation in a patient with mitral and aortic mechanical valve prostheses

PubMed Central

Protasiewicz, Marcin; Gajek, Jacek; Mysiak, Andrzej

2013-01-01

We report a case of a 65-year-old female patient after replacement of aortic and mitral valve with mechanical prostheses and implantation of a pacemaker hospitalized in our clinic due to acute coronary syndrome complicated with cardiac arrest due to ventricular fibrillation. The electrocardiogram performed on admission showed signs of myocardial infarction with concomitant ventricular pacing. After successful resuscitation the coronary angiography was performed, which showed occlusion of the left circumflex artery (LCx) by thrombus. On the basis of intravascular ultrasound imaging the presence of vulnerable plaque, parietal thrombus and dissection of LCx were excluded. It suggested that occlusion of the LCx resulted from its embolism by left-sided heart thrombus due to subtherapeutic oral anticoagulation. In this case suboptimal anticoagulation was partially iatrogenic. Two weeks before the patient had been given vitamin K intravenously due to indeterminable international normalized ratio (INR) level, which caused transient resistance to oral anticoagulants. This case report illustrates tragic difficulties in the treatment with vitamin K antagonists, which concern as many as 2/3 of anticoagulated patients. These troubles contributed to the search for new, more efficient and safer anticoagulants. There are two classes of new oral anticoagulant drugs, which do not require monitoring of coagulation: direct thrombin inhibitors (e.g. dabigatran) and factor Xa inhibitors (e.g. rivaroxaban). In spite of their proven efficacy in the prevention of ischaemic stroke related to atrial fibrillation and prevention or treatment of deep vein thrombosis and pulmonary embolism, the use of new oral anticoagulants for the treatment of patients with mechanical valve prostheses needs further research. PMID:24570697

Cardiac arrest due to left circumflex coronary artery embolism as a complication of subtherapeutic oral anticoagulation in a patient with mitral and aortic mechanical valve prostheses.

PubMed

Protasiewicz, Marcin; Rojek, Aleksandra; Gajek, Jacek; Mysiak, Andrzej

2013-01-01

We report a case of a 65-year-old female patient after replacement of aortic and mitral valve with mechanical prostheses and implantation of a pacemaker hospitalized in our clinic due to acute coronary syndrome complicated with cardiac arrest due to ventricular fibrillation. The electrocardiogram performed on admission showed signs of myocardial infarction with concomitant ventricular pacing. After successful resuscitation the coronary angiography was performed, which showed occlusion of the left circumflex artery (LCx) by thrombus. On the basis of intravascular ultrasound imaging the presence of vulnerable plaque, parietal thrombus and dissection of LCx were excluded. It suggested that occlusion of the LCx resulted from its embolism by left-sided heart thrombus due to subtherapeutic oral anticoagulation. In this case suboptimal anticoagulation was partially iatrogenic. Two weeks before the patient had been given vitamin K intravenously due to indeterminable international normalized ratio (INR) level, which caused transient resistance to oral anticoagulants. This case report illustrates tragic difficulties in the treatment with vitamin K antagonists, which concern as many as 2/3 of anticoagulated patients. These troubles contributed to the search for new, more efficient and safer anticoagulants. There are two classes of new oral anticoagulant drugs, which do not require monitoring of coagulation: direct thrombin inhibitors (e.g. dabigatran) and factor Xa inhibitors (e.g. rivaroxaban). In spite of their proven efficacy in the prevention of ischaemic stroke related to atrial fibrillation and prevention or treatment of deep vein thrombosis and pulmonary embolism, the use of new oral anticoagulants for the treatment of patients with mechanical valve prostheses needs further research.

Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS2 score=1.

PubMed

Gorin, Laurent; Fauchier, Laurent; Nonin, Emilie; de Labriolle, Axel; Haguenoer, Ken; Cosnay, Pierre; Babuty, Dominique; Charbonnier, Bernard

2010-04-01

In patients with atrial fibrillation (AF) and an intermediate risk of stroke (CHADS2 score =1), available evidence from clinical trials is inconclusive and the present guidelines for the management of AF indicate that the choice between oral anticoagulant and aspirin in these patients is open. Our goal was to evaluate whether, in patients with AF and only one moderate risk factor for thromboembolism, treatment with an oral anticoagulant is appreciably more beneficial than treatment with an antiplatelet agent. Among 6,517 unselected patients with AF, 1,012 of them (15.5%) had a CHADS2 score of 1 and were liable to treatment with an antiplatelet agent or an anticoagulant. An oral anticoagulant was prescribed for 606 patients (59.9%) and an antiplatelet agent or no antithrombotic treatment for 406 (40.1%). During follow-up (median=793 days, interquartile range=1,332 days), 105 deaths (10.4%) and 19 strokes (1.9%) were recorded. The administration of an anticoagulant was associated with a lower rate of events (relative risk=0.42, 95% confidence interval 0.29-0.60, p<0.0001) than when no anticoagulant was prescribed. Results remained similar after adjustment for age and other confounding factors. In contrast, prescription of an antiplatelet agent was not associated with a lower risk of events. Factors independently associated with an increased risk of events were older age (p<0.0001), concomitant heart failure (p=0.0002), diabetes (p=0.0025), lack of prescription of an anticoagulant (p<0.0001) and permanent AF (p=0.04). Thus, prescription of an anticoagulant is independently associated with a decreased risk of death or stroke among patients with AF and a CHADS2 score =1.

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.

Areas of improvement in anticoagulant safety. Data from the CACAO study, a cohort in general practice

PubMed Central

Cogneau, Joël; Gaboreau, Yoann; Abenhaïm, Nathan; Bayen, Marc; Calafiore, Matthieu; Guichard, Claude; Jacquet, Jean-Pierre; Lacoin, François; Bertoletti, Laurent

2017-01-01

Background Real-world studies on anticoagulants are mostly performed on health insurance databases, limited to reported events, and sometimes far from every-day issues in family practice. We assess the presence of data for safe monitoring of oral anticoagulants in general practice, and compare patients’ knowledge of taking an anticoagulant between vitamin K antagonists (VKA) and direct anticoagulants (DOAC), and the general practitioner’s perception of their adherence to anticoagulation. Methods The CACAO study is a national cohort study, conducted by general practitioners on ambulatory patients under oral anticoagulant. In the first phase, investigators provided safety data available from medical records at inclusion. They also evaluated patients’ knowledge about anticoagulation and graded their perception of patients’ adherence. Results Between April and December 2014, 463 general practitioners included 7154 patients. Renal and hepatic function tests were respectively unavailable in 109 (7.5%) and 359 (24.7%) DOAC patients. Among patients with atrial fibrillation, 345 patients (6.9%) had a questionable indication of anticoagulant (CHA2DS2-Vasc<2). One hundred and thirty-three VKA patients (2.3%) and 70 DOAC patients (4.9%) answered they took no anticoagulant (p<0.0001). According to general practitioners’ perception, 430 patients (6.1%) were classified as “not very” or “not adherent”, with no difference between groups. Conclusions Our results highlight the efforts needed to improve anticoagulant safety in daily practice: decreasing the rate of unknown biological data in patients with DOACs or the rate of patients with VKA with no strong indication of anticoagulation, and improving patient knowledge with regard to their anticoagulant. Patients’ adherence seems highly over-estimated by the general practitioners. Clinical trial registration ClinicalTrials.gov NCT02376777 PMID:28384199

Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis.

PubMed

van Walraven, Carl; Hart, Robert G; Singer, Daniel E; Laupacis, Andreas; Connolly, Stuart; Petersen, Palle; Koudstaal, Peter J; Chang, Yuchiao; Hellemons, Beppie

2002-11-20

Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke and other vascular events. To compare the risk of vascular and bleeding events in patients with nonvalvular AF treated with vitamin K -inhibiting oral anticoagulants or acetylsalicylic acid (aspirin). Pooled analysis of patient-level data from 6 published, randomized clinical trials. A total of 4052 patients with AF randomly assigned to receive therapeutic doses of oral anticoagulant or aspirin with or without low-dose oral anticoagulants. Ischemic and hemorrhagic stroke, other cardiovascular events, all-cause death, and major bleeding events. Person-year incidence rates were calculated to provide crude comparisons. Relative efficacy was assessed using proportional hazards modeling stratified by study. The variation of the oral anticoagulant's relative effect by pertinent patient factors was explored with interaction terms. All analyses were conducted using the intention-to-treat principle. Patients receiving oral anticoagulant and aspirin were balanced for important prognostic factors. There was no significant heterogeneity between trials in the relative efficacy of oral anticoagulant vs aspirin for any outcome. Patients receiving oral anticoagulant were significantly less likely to experience any stroke (2.4 vs 4.5 events per 100 patient-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71), ischemic stroke (HR, 0.48; 95% CI, 0.37-0.63), or cardiovascular events (HR, 0.71; 95% CI, 0.59-0.85) but were more likely to experience major bleeding (2.2 vs 1.3 events per 100 patient-years; HR, 1.71; 95% CI, 1.21-2.41). The reduction in ischemic stroke risk was similar in patients with paroxysmal AF (1.5 vs 4.7 events per 100 patient-years; HR, 0.32; 95% CI, 0.16-0.61; P<.001). Treating 1000 patients with AF for 1 year with oral anticoagulant rather than aspirin would prevent 23 ischemic strokes while causing 9 additional major bleeds. Overall all-cause survival did not differ but appeared to improve for oral anticoagulant patients 3 years after therapy was started. Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, ischemic strokes, and cardiovascular events for patients with nonvalvular chronic or paroxysmal AF but modestly increases the absolute risk of major bleeding. The balance of benefits and risks varies by patient subgroup.

Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs with Rivaroxaban.

PubMed

Gibson, C M; Hankey, G J; Nafee, T; Welsh, R C

2018-03-22

With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke. Schattauer.

Plasma clot formation and clot lysis to compare effects of different anticoagulation treatments on hemostasis in patients with atrial fibrillation.

PubMed

Königsbrügge, Oliver; Weigel, Günter; Quehenberger, Peter; Pabinger, Ingrid; Ay, Cihan

2018-02-07

The effect of direct oral anticoagulants (DOACs) on turbidimetric measurements of plasma clot formation and susceptibility to fibrinolysis may facilitate a comparison between different classes of anticoagulants in plasma samples. We obtained 424 citrate plasma samples from 226 atrial fibrillation patients on anticoagulation and 24 samples without anticoagulation serving as controls. As comparators, we measured the international normalized ratio (INR) for phenprocoumon samples (N = 166), anti-Xa for low molecular weight heparin (LMWH) samples (N = 42), and DOAC levels with mass spectrometry (dabigatran N = 40, rivaroxaban N = 110, apixaban N = 42). Plasma clot formation and lysis were recorded continuously on a photometer after addition of an activation mix (tissue factor 2 pmol/l and tissue plasminogen activator 333 ng/ml). We used linear regression and ANCOVA for correlation analysis. Clot formation lag phase was prolonged in the presence of anticoagulants in a concentration-dependent manner for DOACs (dabigatran Spearman r = 0.74; rivaroxaban r = 0.78; apixaban r = 0.72, all p < 0.0001), INR dependent for phenprocoumon (r = 0.59, p < 0.0001), anti-Xa level dependent in LMWH samples (r = 0.90, p < 0.0001). Maximum rate of clot formation and peak clot turbidity were reduced in the presence of anticoagulants, but correlated only moderately with the comparator measures of anticoagulation. The clot lysis time was inversely correlated with DOAC concentrations in the presence of recombinant thrombomodulin. A direct ex vivo comparison between the effects of different classes of anticoagulants is possible with turbidimetric measurement of plasma clot formation and lysis. Anticoagulation inhibited clot formation in a plasma concentration manner for DOACs, INR dependent for phenprocoumon, and anti-Xa dependent for LMWH. Susceptibility to fibrinolysis increased with increasing DOAC concentrations.

Satisfaction, quality of life and perception of patients regarding burdens and benefits of vitamin K antagonists compared with direct oral anticoagulants in patients with nonvalvular atrial fibrillation.

PubMed

Contreras Muruaga, Ma Del Mar; Vivancos, José; Reig, Gemma; González, Ayoze; Cardona, Pere; Ramírez-Moreno, José Mª; Martí, Joan; Suárez Fernández, Carmen

2017-06-01

To compare the satisfaction of patients treated with vitamin K antagonists (VKA) with that of patients treated with direct oral anticoagulants (DOACs) and to determine the impact on quality of life of both treatments in patients with nonvalvular atrial fibrillation (NVAF). Cross-sectional multicenter study in which outpatients with NVAF completed the ACTS (Anti-Clot Treatment Scale), SAT-Q (Satisfaction Questionnaire) and EQ-5D-3L (EuroQol 5 dimensions questionnaire, 3 level version) questionnaires. The study population comprised 1337 patients, of whom 587 were taking DOACs and 750 VKAs. Compared with VKAs, DOACs were more commonly prescribed in patients with a history of stroke and in patients with a higher thromboembolic risk. The study scores were as follows: SAT-Q: 63.8 ± 17.8; EQ-5D-3L total score: 75.6 ± 20.9; visual analog scale: 63.1 ± 20.6; ACTS Burdens: 51.8 ± 8.4 and ACTS Benefits: 11.9 ± 2.4. The ACTS Burdens score and ACTS Benefits score were higher with DOACs than with VKAs (54.83 ± 6.11 vs 49.50 ± 9.15; p < 0.001 and 12.36 ± 2.34 vs 11.48 ± 2.46; p < 0.001 respectively). NVAF patients treated with oral anticoagulants had many comorbidities and a high thromboembolic risk. Satisfaction and quality of life with oral anticoagulants were high, although they were both better with DOACs than with VKAs.

[Atrial fibrillation].

PubMed

Spinar, J; Vítovec, J

2003-09-01

Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing with age and associated diseases. The incidence at the age below 60 years is markedly lower than one per cent, whereas in persons above 80 years of age it exceeds six per cent. The occurrence in patients with heart failure is from 10% (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that observed for the first time and permanent, respectively, while transient forms include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on ECG recording, while echocardiography is most significant. The therapy includes two basic questions--anticoagulant or anti-aggregation treatment and the control of rhythm or frequency. The anticoagulant therapy should be introduced in all patients, where contraindications are not present, being necessary before every cardioversion, provided atrial fibrillation lasts more than two days. In patients without any heart disease and with a physiological echocardiogram it is possible to administer only anti-aggregation treatment. Cardioversion (the control of rhythm) is recommended to all symptomatic patients, in other cases and especially in older persons the control of frequency is safer and of more advantage. Electrical cardioversion is more effective that a pharmacological treatment, the sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and digitalis are recommended.

Percutaneous closure of the left atrial appendage for prevention of thromboembolism in atrial fibrillation for patients with contraindication to or failure of oral anticoagulation: a single-center experience.

PubMed

Faustino, Ana; Paiva, Luís; Providência, Rui; Trigo, Joana; Botelho, Ana; Costa, Marco; Leitão-Marques, António

2013-06-01

In non-valvular atrial fibrillation 90% of thrombi originate in the left atrial appendage (LAA). Percutaneous LAA closure has been shown to be non-inferior to warfarin for prevention of thromboembolism. To evaluate the initial experience of a single center in percutaneous LAA closure in patients with high thromboembolic risk and in whom oral anticoagulation was impractical or contraindicated or had failed. Patients with non-valvular atrial fibrillation and CHADS2 score ≥2 in whom oral anticoagulation was impractical or contraindicated or had failed underwent percutaneous LAA closure according to the standard technique. After the procedure, dual antiplatelet therapy was maintained for one month, followed by single antiplatelet therapy indefinitely. Patients were followed by clinical assessment and transthoracic and transesophageal echocardiography. The procedure was performed in 22 of the 23 selected patients (95.7%), mean age 70±9 years, CHADS2 score 3.2±0.9 and CHA2DS2-VASC score 4.7±1.4. Intraprocedural device replacement was necessary only in the first patient, due to oversizing. The following periprocedural complications were observed: one femoral pseudoaneurysm, three femoral hematomas and two minor oropharyngeal bleeds, resolved by local hemostatic measures. During a 12±8 month follow-up a mild peri-device flow and a thrombus adhering to the device, resolved under with enoxaparin therapy, were identified. The rate of transient ischemic attack (TIA)/stroke was lower than expected according to the CHADS2 score (0 vs. 6.7±2.2%). In our initial experience, this procedure proved to be a feasible, safe and effective alternative for atrial fibrillation patients in whom oral anticoagulation is not an option. Only relatively minor complications were observed, with a lower than expected TIA/stroke rate. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Antithrombotic treatment in elderly patients with atrial fibrillation: a practical approach.

PubMed

Suárez Fernández, Carmen; Fernández, Suárez; Formiga, Francesc; Camafort, Miguel; Cepeda Rodrigo, María; Rodrigo, Jose Cepeda; Díez-Manglano, Jesús; Pose Reino, Antonio; Reino, Pose; Tiberio, Gregorio; Mostaza, Jose María

2015-11-04

Atrial fibrillation (AF) in the elderly is a complex condition. It has a direct impact on the underuse of antithrombotic therapy reported in this population. All patients aged ≥75 years with AF have an individual yearly risk of stroke >4 %. However, the risk of hemorrhage is also increased. Moreover, in this population it is common the presence of other comorbidities, cognitive disorders, risk of falls and polymedication. This may lead to an underuse of anticoagulant therapy. Direct oral anticoagulants (DOACs) are at least as effective as conventional therapy, but with lesser risk of intracranial hemorrhage. The simplification of treatment with these drugs may be an advantage in patients with cognitive impairment. The great majority of elderly patients with AF should receive anticoagulant therapy, unless an unequivocal contraindication. DOACs may be the drugs of choice in many elderly patients with AF. In this manuscript, the available evidence about the management of anticoagulation in elderly patients with AF is reviewed. In addition, specific practical recommendations about different controversial issues (i.e. patients with anemia, thrombocytopenia, risk of gastrointestinal bleeding, renal dysfunction, cognitive impairment, risk of falls, polymedication, frailty, etc.) are provided.

[The current role of warfarin].

PubMed

Michalcová, Jana; Buliková, Alena; Zavřelová, Jiřina; Prudková, Marie; Penka, Miroslav

Well-managed warfarin therapy remains an important method of anticoagulation in the 21st century, despite the introduction of new antithrombotics into the clinical practice. The main advantages of warfarin are decades of treatment experience, the possibility to monitor its anticoagulant effect using the INR and the last, but not least, the low cost. Currently, approximately 75 % of anticoagulated patients in the Czech Republic are treated with warfarin and warfarin remains the only option for oral anticoagulant therapy in certain clinical conditions (particularly in patients with valvular atrial fibrillation or mechanical heart valves). For physicians across specialties it is still indispensable to master the basics of safe and effective warfarin therapy, including the management of treatment complications.Key words: anticoagulant therapy - INR - thrombosis - warfarin.

High prevalence of iatrogenic hyperthyroidism in elderly patients with atrial fibrillation in an anticoagulation clinic.

PubMed

Krishnan, Sandeep Kumar; Dohrmann, Mary L; Brietzke, Stephen A; Fleming, David A; Flaker, Greg C

2011-01-01

In elderly patients with established atrial fibrillation (AF) who are receiving thyroid replacement, regular testing for thyroid function is often not performed, placing the patient at risk for iatrogenic hyperthyroidism. Of 215 patients followed in an anticoagulation clinic, 41 were receiving thyroid replacement and 15 of these were found to have hyperthyroidism. Eight had documented AF coincident with abnormal thyroid function. In addition, only 22 patients on thyroid replacement had an annual TSH. In conclusion, iatrogenic hyperthyroidism may frequently be missed in AF patients because of inadequate monitoring of serum TSH. Thyroid replacement is common in elderly patients with AF followed in an anticoagulation clinic. Laboratory evidence of hyperthyroidism occurred in 37%, usually in patients with higher doses of thyroid replacement, and often associated with AF. The frequency of iatrogenic hyperthyroidism may be underestimated in patients with AF since many patients who receive thyroid replacement therapy are not monitored regularly with serum TSH.

Is discharge to home after emergency department cardioversion safe for the treatment of recent-onset atrial fibrillation?

PubMed

von Besser, Kiera; Mills, Angela M

2011-12-01

Recent-onset atrial fibrillation, defined as a first detected or recurrent episode of atrial fibrillation lasting less than 48 hours, is a commonly encountered dysrhythmia in the emergency department (ED). Cardioversion of stable patients in the ED with recent-onset atrial fibrillation without antecedent anticoagulation would allow for these patients to be discharged directly to home. We searched the literature to determine whether any studies have investigated the safety of this management strategy and identified five that addressed this question. These studies are reviewed herein; importantly, not one ED patient who was cardioverted in any of the five studies suffered a thromboembolic event - the feared complication responsible for most of the controversy surrounding the ED management of atrial fibrillation. According to the available evidence, we conclude that it would be within the standard of care to discharge home stable patients with recent-onset atrial fibrillation after cardioversion in the ED with adequate follow-up. It should be noted that although this strategy is safe and effective, the return visit rate for relapsed atrial fibrillation is 3% to 17%, and patients should be made aware of this possibility.

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.

The CHADS2 Score to Predict Stroke Risk in the Absence of Atrial Fibrillation in Hypertensive Patients Aged 65 Years or Older.

PubMed

Morillas, Pedro; Pallarés, Vicente; Fácila, Lorenzo; Llisterri, Jose Luis; Sebastián, María Eugenia; Gómez, Manuel; Castilla, Elena; Camarasa, Raquel; Sandin, Miriam; García-Honrubia, Antonio

2015-06-01

The CHADS2 score is a proven, essential tool for estimating cardioembolic risk (mainly stroke) in patients with nonvalvular atrial fibrillation, with the purpose of determining the indication for anticoagulant therapy. In this study we analyzed the use of CHADS2 in hypertensive patients without known atrial fibrillation in a Mediterranean population. The study included 887 hypertensive patients aged 65 years or older without atrial fibrillation or anticoagulant therapy, who attended a medical consultation. Data on the patients' main risk factors, cardiovascular history, and medication were collected, basic laboratory analyses and electrocardiography were performed, and the CHADS2 score (heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and previous stroke or transient ischemic attack) was calculated. A clinical follow-up was carried out, recording hospital admissions for a stroke or transient ischemic attack. The median duration of follow-up was 804 days. Mean age was 72.5 (SD,5.7) years, 46.6% were men, 27.8% had diabetes, and 8.6% were smokers. During follow-up, 40 patients were hospitalized for a stroke or transient ischemic attack (4.5%). The event-free survival analysis showed significant differences according to the CHADS2 score (log rank test, P < .001). On multivariate analysis, smoking and CHADS2 ≥3 were independent predictors of stroke or transient ischemic attack. The CHADS2 may be useful for estimating the risk of stroke or transient ischemic attack in hypertensive patients without known atrial fibrillation. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

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

Direct oral anticoagulants: An update.

PubMed

Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

2017-12-30

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Budget impact analysis of rivaroxaban vs. warfarin anticoagulation strategy for direct current cardioversion in non-valvular atrial fibrillation patients: the MonaldiVert Economic Study.

PubMed

Russo, Vincenzo; Rago, Anna; Papa, Andrea A; Bianchi, Valter; Tavoletta, Vincenzo; DE Vivo, Stefano; Cavallaro, Ciro; Nigro, Gerardo; D'Onofrio, Antonio

2018-02-01

Rivaroxaban is the first novel oral anticoagulant to receive regulatory approval for non-valvular atrial fibrillation (NVAF) patients who require cardioversion. The MonaldiVert real life experience showed positive benefit-risk profile of short term rivaroxaban administration for transesophageal echocardiogram guided cardioversion in patients who had not achieved adequate pre-procedural vitamin K antagonist (VKA) anticoagulation. Aim of our study was to perform a budget impact analysis of MonaldiVert anticoagulation strategy for direct current cardioversion in NVAF patients and to compare the following costs borne by the Regional Healthcare System (RHS) with those for a hypothetical cohort of identical patients underwent from the beginning to early rivaroxaban treatment before direct current cardioversion. The mean costs per each NVAF patient treated with VKA strategy and rivaroxaban rescue strategy were € 134.53 and € 189.83, respectively. Considering a hypothetical scenario in which all study population would be treated from the beginning with rivaroxaban (rivaroxaban early strategy), the mean cost per patient would have been € 81.11. The total cost borne by the RHS, including the cost of the cardioversion procedure, for the two therapeutic strategies carried out at Monaldi Hospital (VKA strategy and Rivaroxaban rescue strategy) was € 88,458.53. The total cost would be borne by the RHS for rivaroxaban early strategy, if applied to all study population, would have been € 69,989.15 with a saving of € 18,469.38 compared to the actually applied strategy. Rivaroxaban rescue strategy for transesophageal echocardiography guided direct current cardioversion in NVAF patients, who had not achieved adequate pre-procedural VKA anticoagulation, is an effective and safe strategy, which allows to not delay the procedure, reducing times and wastage of cardioversion slots, without substantial costs increase.

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.

Combined Aspirin and Anticoagulant Therapy in Patients with Atrial Fibrillation

PubMed Central

So, Charlotte H.; Eckman, Mark H.

2016-01-01

Background The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. Objective (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Design and Participants Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Main Measures Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Key Results Of 948 patients receiving OAC, 430 (45%) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49% and 42% of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27% had a diagnosis of CAD and 14% had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn’t discontinued. A surprisingly large proportion of patients (22.8%) had no obvious indication for dual therapy. Conclusions Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events. PMID:27665101

Influence of Competing Risks on Estimating the Expected Benefit of Warfarin Among Atrial Fibrillation Patients not Currently Taking Anticoagulants: the ATRIA Study

PubMed Central

Ashburner, Jeffrey M.; Go, Alan S.; Chang, Yuchiao; Fang, Margaret C.; Fredman, Lisa; Applebaum, Katie M.; Singer, Daniel E.

2016-01-01

Background/Objectives To date, studies examining the association between warfarin therapy and incidence of ischemic stroke among patients with atrial fibrillation (AF) have not accounted for the competing risk of death. Competing risk analysis may provide greater understanding of the “real world” impact of anticoagulation on stroke risk over a multiyear time span. Design Cohort study Setting ATRIA Study community-based cohort Participants 13,559 adults with nonvalvular AF between 1996 and 2003. Measurements All events were clinician-adjudicated. We used extended Cox regression with longitudinal warfarin exposure to estimate cause-specific hazard ratios (HR) for thromboembolism (TE) and the competing risk event (all cause death). The Fine and Gray subdistribution regression approach was used to estimate this association while accounting for competing death events. As a secondary analysis, follow-up was limited to 1, 3, and 5-years. Results The rate of death was much higher in the non-warfarin group (8.1 deaths/100 person-years) compared to the warfarin group (5.5 deaths/100 person-years). The cause-specific HR indicated a large reduction in TE with warfarin use (adjusted HR: 0.57, 95% CI: 0.50–0.65). However, after accounting for competing death events, this association was substantially attenuated (adjusted HR: 0.87, 95% CI: 0.77–0.99). In analyses limited to 1-year of follow-up with fewer competing death events, the results for models that did and did not account for competing risks were similar. Conclusion Analyses accounting for competing death events may provide a more realistic estimate of the longer-term stroke prevention benefits of anticoagulants for patients with AF, particularly those who are not currently treated with anticoagulants. PMID:27861698

Left Atrial Appendage Exclusion for Atrial Fibrillation

PubMed Central

Syed, Faisal F.; DeSimone, Christopher V.; Friedman, Paul A.; Asirvatham, Samuel J.

2015-01-01

SYNOPSIS Percutaneous left atrial appendage (LAA) closure is increasingly being used as a treatment strategy to prevent stroke in patients with atrial fibrillation (AF) who have contraindications to anticoagulants. A number of approaches and devices have been developed in the last few years, each with their own unique set of advantages and disadvantages. We review the published studies on surgical and percutaneous approaches to LAA closure; focusing on stroke mechanisms in AF, LAA structure and function relevant to stroke prevention, practical differences in procedural approach, and clinical considerations surrounding management. PMID:25443240

Oral and parenteral anticoagulants: new kids on the block.

PubMed

Aditya, S

2012-01-01

Well-documented drawbacks of traditional anticoagulants have lead to the quest for an ideal anticoagulant resulting in a surge of novel anticoagulant molecules. These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin). Direct thrombin inhibitors and Factor X inhibitors are the most clinically advanced. This article discusses the recent advances in the development of novel targets of anticoagulants. Medline, EMBASE, cochrane database, medscape, SCOPUS, and clinicaltrials.gov were searched using terms "anticoagulants", "blood coagulation inhibitors", "anticoagulants and venous thromboembolism", "anticoagulants and atrial fibrillation", and "'antithrombins." Journal articles published from 2007 to 2012 discussing pharmacology and/or clinical trials were screened.

Fitting the right non-vitamin K antagonist oral anticoagulant to the right patient with non-valvular atrial fibrillation: an evidence-based choice.

PubMed

Li, Yan-Guang; Pastori, Daniele; Lip, Gregory Y H

2018-06-01

Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with an increased risk of ischemic stroke (IS) and systemic embolism (SE). Stroke prevention is a key element for the overall management of AF patients. The non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, apixaban and edoxaban, are at least as effective as warfarin in reducing IS/SE with a lower rate of major bleeding. Various analyses from the large Phase III randomized trials demonstrated different efficacy and safety of NOACs in specific subgroups of patients. The randomized trials are supplemented by effectiveness and safety data from real-world observational cohorts following the availability of these drugs for use in everyday clinical practice. Given the clinical heterogeneity of AF patients, the available data from trials and real-world studies allow us to fit the right NOAC to the particular patient's characteristics, with the aim of optimizing outcomes for the individual patient. This review article aims to provide a summary of the evidence on the performance of NOACs in AF patients with specific clinical characteristics. Evidence-based suggestions are presented to provide a simple and viable strategy for clinicians for the choice of a particular NOAC. KEY MESSAGE Given the different performance of the new-oral anticoagulants in patients with the different clinical situation, evidence-based choice of fitting the right new-oral anticoagulants to the patients is provided in this review article.

Polish and European management strategies in patients with atrial fibrillation. Data from the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot).

PubMed

Lenarczyk, Radosław; Mitręga, Katarzyna; Mazurek, Michał; Janion, Marianna; Opolski, Grzegorz; Drożdż, Jarosław; Streb, Witold; Fuglewicz, Artur; Sokal, Adam; Laroche, Cécile; Lip, Gregory Y H; Kalarus, Zbigniew

2016-01-01

Despite continued efforts of the European Society of Cardiology (ESC) to unify management of patients with atrial fibrillation (AF) across Europe, interregional differences in guideline adherence are likely. The aim of the study was to compare treatment strategies depending on baseline characteristics of AF patients between Poland and other members of the European Union (EU). We analyzed the baseline data and treatment strategies in participants of the ESC registry: the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase. A total of 3119 consecutive patients with AF diagnosed within the last year were included in 67 centers from 9 countries, including 419 patients enrolled in 15 Polish centers. A rhythm control strategy was more frequent in Poland than in other EU countries (20.8% vs 11.9%; P <0.0001). Catheter ablation for AF was also used more frequently in Polish cardiology wards (13.9% vs 8.3%; P = 0.0017), while amiodarone at discharge was used less frequently (12.0% vs 22.7%; P <0.0001). In-hospital use of vitamin K antagonists (VKAs) and non-VKA anticoagulants was less frequent in Polish patients with a CHA2DS2-VASc score of 2 or higher than in patients from other EU countries (61.1% vs 79.0%; P <0.0001), but overall anticoagulation rates at discharge were similar to those in other countries (83.3% vs 82.6%). A rhythm control-oriented strategy in patients with AF with the use of ablation in cardiology wards is more frequent in Poland than in other EU countries. Similar to other EU countries, compliance with the ESC guidelines regarding anticoagulation in AF patients is suboptimal in Poland. Undertreatment was observed in a significant proportion of patients at high risk of stroke, while a large group of low-risk patients are overtreated. Differences between the types of recruiting centers in Poland and other EU countries might have influenced the results.

The changing characteristics of atrial fibrillation patients treated with warfarin.

PubMed

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

2015-11-01

It has been suggested that direct oral anticoagulants are being preferentially used in low risk atrial fibrillation (AF) patients. Understanding the changing risk profile of new AF patients treated with warfarin is important for interpreting the quality of warfarin delivery through an anticoagulation clinic. Six anticoagulation clinics participating in the Michigan Anticoagulation Quality Improvement Initiative enrolled 1293 AF patients between 2010 and 2014 as an inception cohort. Abstracted data included demographics, comorbidities, medication use and all INR values. Risk scores including CHADS2, CHA2DS2-VASc, HAS-BLED, SAMe-TT2R2, and Charlson comorbidity index (CCI) were calculated for each patient at the time of warfarin initiation. The quality of anticoagulation was assessed using the Rosendaal time in the therapeutic range (TTR) during the first 6 months of treatment. Between 2010 and 2014, patients initiating warfarin therapy for AF had an increasing mean CHADS2 (2.0 ± 1.1 to 2.2 ± 1.4, p = 0.02) and CCI (4.7 ± 1.8 to 5.1 ± 2.0, p = 0.03), and a trend towards increasing mean CHA2DS2-VASc, HAS-BLED, and SAMe-TT2R2 scores. The actual TTR remained unchanged over the study period (62.6 ± 18.2 to 62.7 ± 17.0, p = 0.98), and the number of INR checks did not change (18.9 ± 5.2 to 18.5 ± 5.1, p = 0.06). Between 2010 and 2014, AF patients newly starting warfarin had mild increases in risk for stroke and death with sustained quality of warfarin therapy.

Bleeding events associated with novel anticoagulants: a case series.

PubMed

Mirzaee, Sam; Tran, Tara Thi Thien; Amerena, John

2013-12-01

Until lately warfarin was the only valuable oral anticoagulant in stroke reduction in high risk cases with non valvular atrial fibrillation (NVAF). Although with warfarin the rate of stroke reduced notably, the major concern is the risk of serious bleeding and difficulty of establishing and maintaining the international normalised ratio (INR) within the therapeutic range. With the development of the novel anticoagulants we now have for the first time since the innovation of Warfarin feasible alternatives to it to decrease stroke rates in high risk patients with NVAF. To diminish adverse bleeding events with the novel anticoagulant proper selection of patients prior starting treatment is essential. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Benefit, risk and cost of new oral anticoagulants and warfarin in atrial fibrillation; A multicriteria decision analysis.

PubMed

Mendoza-Sanchez, Jose; Silva, Federico; Rangel, Lady; Jaramillo, Linda; Mendoza, Leidy; Garzon, Jenny; Quiroga, Andrea

2018-01-01

Warfarin and new oral anticoagulants are effective in reducing stroke in atrial fibrillation; however, the benefits and risks rates in clinical trials show heterogeneity for each anticoagulant, and is unknown the cost influence on a model considering most of the treatment consequences. We designed a benefit-risk and cost assessment of oral anticoagulants. We followed the roadmap proposed by IMI-PROTECT and the considerations of emerged good practice to perform Multi-Criteria Decision Analysis (MCDA). The roadmap defines the following steps: (1) planning, (2) evidence gathering and data preparation, (3) analyses, (4) explorations, and (5) conclusions. We defined two reference points (0-100) to allocate numerical values for scores and weights, and used an analogue numeric scale to assess physicians' preferences. As benefits of the anticoagulant therapy, we included reductions in stroke and all-cause mortality; intracranial haemorrhage, gastrointestinal haemorrhage, minor bleeding and myocardial infarction were considered risks. We also made an estimation of the annual drug cost per person. The scores were: Apixaban 33, Dabigatrán 25, warfarin 18 and Rivaroxaban 14 this score reveals the most preferred up to the less preferred option, considering the benefit-risk ratio and drug costs altogether. The relative model weights were: 51.1% for risks, 40.4% for benefits and 8.5% for cost. The sensitivity analysis confirms the model robustness. From this analysis, apixaban should be considered as the preferred anticoagulant option -due to a better benefit-risk balance and a minor cost influence- followed by dabigatran, warfarin and rivaroxaban.

Differences in attitude, education, and knowledge about oral anticoagulation therapy among patients with atrial fibrillation in Europe: result of a self-assessment patient survey conducted by the European Heart Rhythm Association.

PubMed

Hernández Madrid, Antonio; Potpara, Tatjana S; Dagres, Nikolaos; Chen, Jian; Larsen, Torben B; Estner, Heidi; Todd, Derick; Bongiorni, Maria G; Sciaraffia, Elena; Proclemer, Alessandro; Cheggour, Saida; Amara, Walid; Blomstrom-Lundqvist, Carina

2016-03-01

The purpose of this patient survey was to analyse the knowledge about blood thinning medications relative to gender, age, education, and region of residence in patients with atrial fibrillation (AF). A total of 1147 patients with AF [mean age 66 ± 13 years, 529 (45%) women] from eight European countries responded to this survey. Most patients understood that the indication for anticoagulation therapy was to 'thin the blood', but 8.1% responded that the purpose of the medication was to treat the arrhythmia. Patients with college or university grades reported less frequent deviations from their target INR range compared with those without schooling (2.8% vs. 5.1%, P < 0.05). The awareness of anticoagulation-related risk of bleedings was lowest in patients without schooling (38.5%) and highest in those with college and university education (57.0%), P < 0.05. The same pattern was also observed regarding patient's awareness of non-vitamin K antagonist oral anticoagulants (NOACs): 56.5% of the patients with university education and only 20.5% of those without schooling (P < 0.05) knew about NOACs, indicating that information about new anticoagulation therapies remains well below the target. Bleeding events were statistically less frequent in patients on NOACs compared with vitamin K antagonists. The education level and patients' knowledge have a direct influence on the global management of the anticoagulation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Embolic risk in atrial fibrillation that arises from hyperthyroidism: review of the medical literature.

PubMed

Traube, Elie; Coplan, Neil L

2011-01-01

Atrial fibrillation, the most common cardiac complication of hyperthyroidism, occurs in an estimated 10% to 25% of overtly hyperthyroid patients. The prevalence of atrial fibrillation increases with age in the general population and in thyrotoxic patients. Other risk factors for atrial fibrillation in thyrotoxic patients include male sex, ischemic or valvular heart disease, and congestive heart failure. The incidence of arterial embolism or stroke in thyrotoxic atrial fibrillation is less clear. There are many reports of arterial thromboembolism associated with hyperthyroidism, including cases of young adults without coexisting risk factors other than thyrotoxic atrial fibrillation. The use of anticoagulative agents to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation is controversial: National organizations provide conflicting recommendations in their practice guidelines. Herein, we review the medical literature and examine the evidence behind the recommendations in order to determine the best approach to thromboembolic prophylaxis in patients who have atrial fibrillation that is associated with hyperthyroidism.

Embolic Risk in Atrial Fibrillation that Arises from Hyperthyroidism

PubMed Central

Traube, Elie; Coplan, Neil L.

2011-01-01

Atrial fibrillation, the most common cardiac complication of hyperthyroidism, occurs in an estimated 10% to 25% of overtly hyperthyroid patients. The prevalence of atrial fibrillation increases with age in the general population and in thyrotoxic patients. Other risk factors for atrial fibrillation in thyrotoxic patients include male sex, ischemic or valvular heart disease, and congestive heart failure. The incidence of arterial embolism or stroke in thyrotoxic atrial fibrillation is less clear. There are many reports of arterial thromboembolism associated with hyperthyroidism, including cases of young adults without coexisting risk factors other than thyrotoxic atrial fibrillation. The use of anticoagulative agents to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation is controversial: national organizations provide conflicting recommendations in their practice guidelines. Herein, we review the medical literature and examine the evidence behind the recommendations in order to determine the best approach to thromboembolic prophylaxis in patients who have atrial fibrillation that is associated with hyperthyroidism. PMID:21720457

Predictors of self-reported adherence to direct oral anticoagulation in a population of elderly men and women with non-valvular atrial fibrillation.

PubMed

Rossi, Andrea P; Facchinetti, Roberto; Ferrari, Elena; Nori, Nicole; Sant, Selena; Masciocchi, Elena; Zoico, Elena; Fantin, Francesco; Mazzali, Gloria; Zamboni, Mauro

2018-05-14

There is a general lack of studies evaluating medication adherence with self-report scales for elderly patients in treatment with direct oral anticoagulants (DOACs). The aim of the study was to assess the degree of adherence to DOAC therapy in a population of elderly outpatients aged 65 years or older affected by non-valvular atrial fibrillation (NVAF), using the 4-item Morisky Medication Adherence Scale, and to identify potential factors, including the geriatric multidimensional evaluation, which can affect adherence in the study population. A total of 103 subjects, anticoagulated with DOACs for NVAF in primary or secondary prevention, were eligible; 76 showed adequate adhesion to anticoagulant therapy, while 27 showed inadequate adherence. Participants underwent biochemical assessment and Morisky Scale, Instrumental Activities of Daily Living, CHA2DS2-VASc, HAS-BLED, mental status and nutritional evaluations were performed. 2% of subjects assumed Dabigatran at low dose, while 7.8% at standard dose, 9.7% assumed low-dose of Rivaroxaban and 30.1% at standard dose, 6.8% assumed Apixaban at low dose and 39.7% at standard dose, and finally 1% assumed Edoxaban at low dose and 2.9% at standard dose. Most subjects took the DOACs without help (80.6%), while 16 subjects were helped by a family member (15.5%) and 4 were assisted by a caregiver (3.9%). Binary logistic regression considered inappropriate adherence as a dependent variable, while age, male sex, polypharmacotherapy, cognitive decay, caregiver help for therapy assumption, duration of DOAC therapy and double daily administration were considered as independent variables. The double daily administration was an independent factor, determining inappropriate adherence with an OR of 2.88 (p = 0.048, CI 1.003-8.286).

[Low molecular weight heparin and non valvular atrial fibrillation].

PubMed

Ederhy, S; Di Angelantonio, E; Meuleman, C; Janower, S; Boccara, F; Cohen, A

2006-12-01

Low molecular weight heparin (LMWH) are obtained through chemical or enzyme depolymerisation of unfractioned heparins (UFH). LMWHs present several advantages over UFH: they exhibit a smaller interindividual variability of the anticoagulant effect, they have a greater bioavailability, a longer plasma half-life and do not require monitoring of the anticoagulant effect. LMWH have restrictive indications in AF patients, cardioversion (II level C and TEE for ACC/AHA/ESC and 2C for ACCP guidelines) or use as a bridge therapy (IIB, level C for ACC/AHA/ESC). The ACE study (Anticoagulation for cardioversion using enoxaparin), showed a reduction, though not statistically significant, of 42% of the composite end point (embolic event, major bleeding and death) 2.8% under enoxaparin vs. 4.8 % under conventional treatment, relative risk 0.58, CI 95% 0.23-1.46). Other studies, using dalteparin, confirmed that an anticoagulant treatment using LMWH followed by warfarin was at least as good as conventional management. ACUTE II (Assessment of cardioversion using transesophageal echochardiography), a randomized multicenter trial, compared the efficacy and tolerance of enoxaparin (1 mg/kg every 12 hours) and UFH in 155 patients eligible for a TEE-guided cardioversion. These patients were administered LMWH or UFH for 24 hours before TEE or cardioversion. There were no significative differences regarding the incidence of the study end points, in particular stroke and bleeding, and no death occurred. HAEST (Heparin in acute embolic stroke trial), a randomized, placebo-controlled, double blind trial failed to show the LMWH superiority over aspirin in patients with acute ischemic stroke and atrial fibrillation. Finally, LMWH have been proposed as a bridge therapy in patients under chronic VKA prior to surgery or invasive procedures. This strategy resulted in a low rate of thromboembolic events and major bleedings.

The safety and persistence of non-vitamin-K-antagonist oral anticoagulants in atrial fibrillation patients treated in a well structured atrial fibrillation clinic.

PubMed

Al-Khalili, Faris; Lindström, Catrine; Benson, Lina

2016-01-01

To examine the long-term persistence and safety of the non-vitamin-K-antagonist oral anticoagulants (NOACs) dabigatran (D), rivaroxaban (R) and apixaban (A) in patients with non-valvular atrial fibrillation (AF) treated in the framework of a well structured, nurse-based AF unit for initiation and follow-up of NOAC. Retrospective clinical data were collected for 766 consequent patients from a single cardiology outpatient clinic incorporating the AF unit. The follow-up time, median (q1-q3), was 367 days (183-493) for D patients (n = 233), 432 days (255-546) for R patients (n = 282) and 348 days (267-419) for A patients (n = 251). No significant differences were found between the three groups with regard to age, sex, renal function, or CHA2DS2-VASc score. For all bleeding events the incidence rates per 100 patient-years of follow-up (95% confidence interval [CI], p-value) were reported more often for treatment with R (17.2, 12.7-22.8) than for D (7.0, 4.0-11.3, p = 0.001) and A (8.7, 5.2-13.6, p = 0.013). The differences remained significant after adjustment for clinically relevant variables. Discontinuation rates (n = 167) were lower for A (11.5, 7.5-16.8) than for D (30, 23.4-37.9, p < 0.001) and R (23.9, 18.6-30.1, p = 0.001), and were mainly attributed to drug-specific side effects and bleedings. The majority of discontinued patients (n = 142, 85%) proceeded with other types of oral anticoagulants. The main limitation of the study is the small patient population with a short follow-up time. In a retrospective study at a single AF clinic, NOACs showed significantly different bleeding rates and varied discontinuation rates when compared to each other, related mainly to agent-specific side effects and bleedings. The majority of patients that discontinued proceeded with other types of oral anticoagulant.

Bleeding risk in patients with atrial fibrillation: the AMADEUS study.

PubMed

Lane, Deirdre A; Kamphuisen, Pieter W; Minini, Pascal; Büller, Harry R; Lip, Gregory Y H

2011-07-01

This study aimed to assess the impact of combination antithrombotic therapy on stroke and bleeding risk compared with anticoagulation therapy only in patients with atrial fibrillation (AF). Post hoc analysis of 4,576 patients with AF (mean ± SD age, 70.1 ± 9.1 years; men, 66.5%) enrolled in the Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation (AMADEUS) trial were randomized to receive either subcutaneous idraparinux (2.5 mg weekly) (n = 2,283) or dose-adjusted vitamin K antagonists (VKAs) (international normalized ratio, 2.0-3.0) (n = 2,293). Of these patients, 848 (18.5%) received antiplatelet therapy (aspirin, clopidogrel, ticlopidine, etc) in addition to anticoagulation treatment (combination antithrombotic therapy). A total of 572 (15.3% per year) clinically relevant bleeding and 103 (2.6% per year) major bleeding events occurred. Patients receiving combination antithrombotic therapy had a 2.3- to 2.5-fold increased risk of clinically relevant bleeding events and major bleeding events, respectively, compared with those receiving anticoagulation therapy only. Multivariate analyses (hazard ratio, 95% CI) revealed that the risk of clinically relevant bleeding was significantly increased by age 65 to 74 years (1.44, 1.14-1.82) and ≥ 75 years (1.59, 1.24-2.04, P = .001) and by combination antithrombotic therapy (2.47, 2.07-2.96, P < .0001). The same held true for major bleeding events, with analogous figures for age 65 to 74 years (2.26, 1.08-4.71) and ≥ 75 years (4.19, 1.98-8.87, P = .0004) and for combination antithrombotic therapy (2.23, 1.49-3.34, P < .0001). Combination antithrombotic therapy was not associated with a decrease in ischemic stroke risk compared with anticoagulation therapy only (11 [1.4% per year] vs 22 [0.7% per year]; adjusted hazard ratio, 2.01; 95% CI, 0.94-4.30; P = .07). Combination antithrombotic therapy increases the risk of clinically relevant bleeding and major bleeding in patients with AF and does not appear to reduce the risk of stroke.

The Effect of a Clinical Decision Support System on Improving Adherence to Guideline in the Treatment of Atrial Fibrillation: An Interrupted Time Series Study.

PubMed

Sheibani, Reza; Sheibani, Mehdi; Heidari-Bakavoli, Alireza; Abu-Hanna, Ameen; Eslami, Saeid

2017-12-23

To evaluate the effect of a computerized Decision Support System (CDSS) on improving adherence to an anticoagulation guideline for the treatment of atrial fibrillation (AF). This study had an interrupted time series design. The adherence to the guideline was assessed at fortnightly (two weeks) intervals from January 2016 to January 2017, 6 months before and 6 months after intervention. Newly diagnosed patients with AF were included in the offices of ten cardiologists. Stroke and major bleeding risks were calculated by the CDSS which was implemented via a mobile application. Treatment recommendations based on the guideline were shown to cardiologists. The segmented regression model was used to evaluate the effect of CDSS on level and trend of guideline adherence for the treatment of AF. In our analysis, 373 patients were included. The trend of adherence to the anticoagulation guideline for the treatment of AF was stable in the pre-intervention phase. After the CDSS intervention, mean of the adherence to the guideline significantly increased from 48% to 65.5% (P-value < 0.0001). The trend of adherence to the guideline was stable in the post-intervention phase. Our results showed that the CDSS can improve adherence to the anticoagulation guideline for the treatment of AF. Registration ID: IRCT2016052528070N1.

Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation.

PubMed

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

2014-05-01

Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation. We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from 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). Cox proportional hazards modeling was used. During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10(9)/L (1.08; 1.02-1.13 per 10×10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73). Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.

Thyrotoxic atrial fibrillation.

PubMed

Parmar, Malvinder S

2005-01-04

Atrial fibrillation is the most common cardiac complication of hyperthyroidism and occurs in 15% of patients with hyperthyroidism. It is associated with a higher risk of thromboembolism that often involves the central nervous system. Oral anticoagulation is important in the majority of these patients to prevent thromboembolic complications. These patients require adjustment in the dose of various rate-controlling agents because of increased clearance associated with hyperthyroidism and a decrease in warfarin dosage because of increased clearance of vitamin K-dependent clotting factors. The management of thyrotoxic atrial fibrillation is summarized in this clinical review.

Use of Guidelines for Reducing Stroke Risk in Patients With Nonvalvular Atrial Fibrillation: A Review From a Latin American Perspective

PubMed Central

Silva, Gisele Sampaio; Ameriso, Sebastián F.

2017-01-01

Atrial fibrillation (AF) is a prominent risk factor for stroke and a leading cause of death and disability throughout Latin America. Contemporary evidence-based guidelines for the management of AF and stroke incorporate the use of practical and relatively simple scoring methods to estimate both stroke and bleeding risk, in order to assist in matching patients with appropriate interventions. This review examines consistencies and differences among guidelines for reducing stroke risk in patients with AF, assessing the role of user-friendly scoring methods to determine appropriate patients for anticoagulation and other treatment options. Current options include warfarin and direct oral anticoagulants such as dabigatran, rivaroxaban, apixaban, and edoxaban. These agents have been found to be superior or noninferior to standard vitamin K antagonist anticoagulation in large randomized trials. Potential benefits of these agents mainly include lower ischemic stroke rates, reduced intracranial bleeding, no need for regular monitoring, and fewer drug–drug and drug–food interactions. Expert opinions regarding clinical situations for which data are presently lacking, such as emergency bleeding and stroke in anticoagulated patients, are also provided. Enhanced attention and adherence to evidence-based guidelines are essential components for a strategy to reduce stroke morbidity and mortality across Latin America. PMID:28992764

Peri-operative Adverse Outcomes in Patients with Atrial Fibrillation Taking Warfarin or Edoxaban: Analysis of the ENGAGE AF-TIMI 48 Trial.

PubMed

Douketis, James D; Murphy, Sabina A; Antman, Elliott M; Grip, Laura T; Mercuri, Michele F; Ruff, Christian T; Weitz, Jeffrey I; Braunwald, Eugene; Giugliano, Robert P

2018-06-01

 Peri-operative management of anticoagulated patients with atrial fibrillation (AF) is challenging. To gain information on the peri-operative management of edoxaban, we compared outcomes in patients on warfarin or edoxaban enrolled in ENGAGE AF-TIMI 48 who underwent a surgery or invasive procedure.  Data from patients undergoing their first surgery/procedure were analysed and results compared by anticoagulant (warfarin vs. higher- or lower-dose edoxaban regimen [HDER and LDER, respectively]). Patients were classified by procedural management: anticoagulant interrupted (last dose 4-10 days pre-procedure) or anticoagulant continued (last dose ≤ 3 days pre-procedure). Stroke/systemic embolism (SSE), major bleeding (MB), MB or clinically relevant non-MB (CRNMB) and death were assessed from 7 days pre- until 30 days post-procedure. The chi-square test was used to compare outcomes across treatment groups.  A total of 7,193 patients (34%) underwent surgery/procedure: 3,116 had anticoagulant interrupted, 4,077 had anticoagulant continued. Among patients on warfarin, HDER and LDER who had anticoagulant interrupted, rates of SSE were 0.6, 0.5 and 0.9% ( p  = 0.53), rates of MB were 1.0, 1.2 and 1.1% ( p  = 0.94) and rates of MB or CRNMB were 3.9, 4.2 and 3.6% ( p  = 0.78); among patients on warfarin, HDER and LDER who had anticoagulant continued, rates of SSE were 1.1, 0.7 and 0.9% ( p  = 0.51), rates of MB were 3.6, 2.6 and 2.4% ( p  = 0.13) and rates of MB or CRNMB were 8.5, 7.9 and 6.6% ( p  = 0.17).  In patients requiring surgery/procedure in ENGAGE AF-TIMI 48, peri-operative rates of SSE, MB and death were not significantly different in patients who received edoxaban or warfarin. Schattauer GmbH Stuttgart.

Trends in hospitalization for atrial fibrillation: epidemiology, cost, and implications for the future.

PubMed

Sheikh, Azfar; Patel, Nileshkumar J; Nalluri, Nikhil; Agnihotri, Kanishk; Spagnola, Jonathan; Patel, Aashay; Asti, Deepak; Kanotra, Ritesh; Khan, Hafiz; Savani, Chirag; Arora, Shilpkumar; Patel, Nilay; Thakkar, Badal; Patel, Neil; Pau, Dhaval; Badheka, Apurva O; Deshmukh, Abhishek; Kowalski, Marcin; Viles-Gonzalez, Juan; Paydak, Hakan

2015-01-01

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide and the most common arrhythmia leading to hospitalization. Due to a substantial increase in incidence and prevalence of AF over the past few decades, it attributes to an extensive economic and public health burden. The increasing number of hospitalizations, aging population, anticoagulation management, and increasing trend for disposition to a skilled facility are drivers of the increasing cost associated with AF. There has been significant progress in AF management with the release of new oral anticoagulants, use of left atrial catheter ablation, and novel techniques for left atrial appendage closure. In this article, we aim to review the trends in epidemiology, hospitalization, and cost of AF along with its future implications on public health. Published by Elsevier 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 anticoagulants and nursing: an approach from patient's safety.

PubMed

Romero Ruiz, Adolfo; Romero-Arana, Adolfo; Gómez-Salgado, Juan

In recent years, a new line of treatment for the prevention of stroke in non-valvular atrial fibrillation, the so-called direct anticoagulants or new anticoagulants has appeared. The proper management and follow-up of these patients is essential to minimize their side effects and ensure patient safety. In this article, a description of these drugs is given, analyzing their characteristics, functioning and interactions together with the most habitual nursing interventions, as well as a reflection on the implications for the practice. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Stroke Prevention in Atrial Fibrillation: Focus on Latin America

PubMed Central

Massaro, Ayrton R.; Lippp, Gregory Y. H.

2016-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with an estimated prevalence of 1-2% in North America and Europe. The increased prevalence of AF in Latin America is associated with an ageing general population, along with poor control of key risk factors, including hypertension. As a result, stroke prevalence and associated mortality have increased dramatically in the region. Therefore, the need for effective anticoagulation strategies in Latin America is clear. The aim of this review is to provide a contemporary overview of anticoagulants for stroke prevention. The use of vitamin K antagonists (VKAs, eg, warfarin) and aspirin in the prevention of stroke in patients with AF in Latin America remains common, although around one fifth of all AF patients receive no anticoagulation. Warfarin use is complicated by a lack of access to effective monitoring services coupled with an unpredictable pharmacokinetic profile. The overuse of aspirin is associated with significant bleeding risks and reduced efficacy for stroke prevention in this patient group. The non-VKA oral anticoagulants (NOACbs) represent a potential means of overcoming many limitations associated with VKA and aspirin use, including a reduction in the need for monitoring and a reduced risk of hemorrhagic events. The ultimate decision of which anticoagulant drug to utilize in AF patients depends on a multitude of factors. More research is needed to appreciate the impact of these factors in the Latin American population and thereby reduce the burden of AF-associated stroke in this region. PMID:28558081

Relation of quality of anticoagulation control with different management systems among patients with atrial fibrillation: Data from FANTASIIA Registry.

PubMed

Roldán Rabadán, Inmaculada; Esteve-Pastor, María Asunción; Anguita-Sánchez, Manuel; Muñiz, Javier; Camacho Siles, José; Quesada, María Angustias; Ruiz Ortiz, Martín; Marín, Francisco; Martínez Sellés, Manuel; Bertomeu, Vicente; Lip, Gregory Y H; Cequier Fillat, Angel; Badimón, Lina

2018-05-01

Anticoagulation control in patients with atrial fibrillation (AF) has a multidisciplinary approach although is usually managed by general practitioners (GP) or haematologists. The aim of our study was to assess the quality of anticoagulation control with vitamin K antagonists (VKAs) in relation to the responsible specialist in a "real-world" AF population. We consecutively enrolled VKA anticoagulated patients included in the FANTASIIA Registry from 2013 to 2015. We analysed demographical, clinical characteristics and the quality of anticoagulation control according to the specialist responsible (ie GPs or haematologists). Data on 1584 patients were included (42.5% females, mean age 74.0 ± 9.4 years): 977 (61.7%) patients were controlled by GPs and 607 (38.3%) by haematologists. Patients managed by GPs had higher previous heart disease (53.2% vs 43.3%, P < .001), heart failure (32.9% vs 26.5%, P < .008) and dilated cardiomyopathy (15.2% vs 8.7%, P < .001) with better renal function (69.3 ± 24.7 vs 63.1 ± 21.4 mL/min, P < .001) compared to patients managed by haematologists. There was no difference between groups in the type of AF, CHA 2 DS 2 -VASc or HAS-BLED scores, but patients with electrical cardioversion were more prevalent in GP group. The overall mean time in therapeutic range (TTR) assessed by Rosendaal method was 61.5 ± 24.9%; 52.6% of patients had TTR<65% and 60% of patients had TTR<70%. TTR was significantly lower in patients controlled by haematologists than by GPs (63 ± 24.4 vs 59.2 ± 25.6, P < .005). About 60% of AF patients anticoagulated with VKAs had poor anticoagulation control (ie TTR<70%), and their management was only slightly better than when it is managed by general practitioners. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Genetic and Non-Genetic Factors Affecting the Quality of Anticoagulation Control and Vascular Events in Atrial Fibrillation.

PubMed

Park, Yun Kyung; Lee, Mi Ji; Kim, Jae Ha; Lee, Jin Soo; Park, Rae Woong; Kim, Gyeong-Moon; Chung, Chin-Sang; Lee, Kwang Ho; Kim, June Soo; Lee, Soo-Youn; Bang, Oh Young

2017-06-01

Warfarin has a narrow therapeutic window. We hypothesized that genetic factors related to warfarin metabolism (CYP2C9) and activity (VKORC1) would show stronger associations than modifiable factors with the quality of anticoagulation control and risks for thromboembolism and hemorrhage. In this retrospective cohort analysis, clinical and genetic data were collected from 380 patients with atrial fibrillation (AF) who were followed for an average observation period of 4 years. We evaluated the factors associated with time in therapeutic range (TTR, international normalized ratio [INR]: 2-3) and vascular events (either thromboembolic or hemorrhagic), including both genetic (CYP2C9 and VKORC1 genotype) and modifiable factors (anticoagulation service and warfarin dose assessment interval). The genotypic frequency of CYP2C9*3 (rs1057910) was 9.5% and that of VKORC1 1173C>T (rs9934438) was 16.3%. TTR showed dependence on VKORC1 polymorphism: TTR was higher in carriers of the VKORC1 1173C>T than of the VKORC1 TT genotype (61.7 ± 16.0% versus 56.7 ± 17.4%, P = .031). Multivariate testing showed that the VKORC1 genotype and anticoagulation service were independently related to labile INRs (TTR <65%). Vascular events were observed in 66 patients (18.4%) during the study period. A Cox proportional hazard model showed that the use of anticoagulation service and patients' characteristics, such as AF-thromboembolic risk (CHA 2 DS 2 -VASc score: Congestive heart failure, Hypertension, Age 75 years or older, Diabetes mellitus, previous Stroke or transient ischemic attack, Vascular disease, Age 65 to 74 years, female) and consequence (neurologic disability), but not genetic factors, were independently associated with vascular events. Both genetic factor (VKORC1 genotype) and clinical efforts (anticoagulation service) influenced the quality of anticoagulation control. However, clinical events were more strongly associated with patient characteristics and clinical efforts than with genetic factors. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Rationale and design of the Atrial Fibrillation health Literacy Information Technology Trial: (AF-LITT).

PubMed

Guhl, Emily N; Schlusser, Courtney L; Henault, Lori E; Bickmore, Timothy W; Kimani, Everlyne; Paasche-Orlow, Michael K; Magnani, Jared W

2017-11-01

Atrial Fibrillation (AF) is a common cardiac arrhythmia that is challenging for patients and adversely impacts health-related quality of life (HRQoL). Long-term management of AF requires that patients adhere to complex therapies, understand difficult terminology, navigate subspecialty care, and have continued symptom monitoring with the goal of preventing adverse outcomes. Continued interventions to ameliorate the patient experience of AF are essential. The Atrial Fibrillation health Literacy Information Technology Trial (AF-LITT; NCT03093558) is an investigator-initiated, 2-arm randomized clinical trial (RCT). This RCT is a pilot in order to implement a novel, smartphone-based intervention to address the patient experience of AF. This pilot RCT will compare a combination of the Embodied Conversational Agent (ECA) and the Alive Cor Kardia Mobile heart rhythm monitor to the current standard of care. The study will enroll 180 adults with non-valvular AF who are receiving anticoagulation for stroke prevention and randomize them to receive a 30-day intervention (smartphone-based ECA/Kardia) or standard of care, which will include a symptom and adherence journal. The primary end-points are improvement in HRQoL and self-reported adherence to anticoagulation. The secondary end-points are the acceptability of the intervention to participants, its use by participants, and acceptability to referring physicians. The AF-LITT pilot aims to evaluate the efficacy of the ECA/Kardia to improve HRQoL and anticoagulant adherence, and to guide its implementation in a larger, multicenter clinical trial. The intervention has potential to improve HRQoL, adherence, and health care utilization in individuals with chronic AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Rationale and design of the Atrial Fibrillation health Literacy Information Technology Trial: (AF-LITT)

PubMed Central

Guhl, Emily N.; Schlusser, Courtney L.; Henault, Lori E.; Bickmore, Timothy W.; Kimani, Everlyne; Paasche-Orlow, Michael K.; Magnani, Jared W.

2017-01-01

Background Atrial Fibrillation (AF) is a common cardiac arrhythmia that is challenging for patients and adversely impacts health-related quality of life (HRQoL). Long-term management of AF requires that patients adhere to complex therapies, understand difficult terminology, navigate subspecialty care, and have continued symptom monitoring with the goal of preventing adverse outcomes. Continued interventions to ameliorate the patient experience of AF are essential. Design The Atrial Fibrillation health Literacy Information Technology Trial (AF-LITT; NCT03093558) is an investigator-initiated, 2-arm randomized clinical trial (RCT). This RCT is a pilot in order to implement a novel, smartphone-based intervention to address the patient experience of AF. This pilot RCT will compare a combination of the embodied conversational agent (ECA) and the Alive Cor Kardia Mobile heart rhythm monitor to the current standard of care. The study will enroll 180 adults with non-valvular AF who are receiving anticoagulation for stroke prevention and randomize them to receive a 30-day intervention (smartphone-based ECA/Kardia) or standard of care, which will include a symptom and adherence journal. The primary end-points are improvement in HRQoL and self-reported adherence to anticoagulation. The secondary end-points are the acceptability of the intervention to participants, its use by participants, and acceptability to referring physicians. Conclusions The AF-LITT pilot aims to evaluate the efficacy of the ECA/Kardia to improve HRQoL and anticoagulant adherence, and to guide its implementation in a larger, multicenter clinical trial. The intervention has potential to improve HRQoL, adherence, and health care utilization in individuals with chronic AF. PMID:28923492

Effectiveness and Safety of Dabigatran and Warfarin in Real‐World US Patients With Non‐Valvular Atrial Fibrillation: A Retrospective Cohort Study

PubMed Central

Lauffenburger, Julie C.; Farley, Joel F.; Gehi, Anil K.; Rhoney, Denise H.; Brookhart, M. Alan; Fang, Gang

2015-01-01

Background The recent availability of dabigatran, a novel oral anticoagulant, provided a new treatment option for stroke prevention in atrial fibrillation beyond warfarin, the main therapy for years. Little is known about their real‐world comparative effectiveness and safety, even less among patient demographic and clinical subgroups. Methods and Results Using a cohort of non‐valvular AF patients initiating anticoagulation from October 2010 to December 2012 drawn from a large US database of commercial and Medicare supplement claims, we applied propensity score weights to Cox proportional hazards regression to assess the comparative effectiveness and safety of dabigatran versus warfarin. Analyses were repeated among clinical and demographic subgroups using stratum‐specific propensity scores as an exploratory analysis. Of the 64 935 patients initiating anticoagulation, 32.5% used dabigatran. Compared with warfarin, dabigatran was associated with a lower risk of ischemic stroke or systemic embolism (composite adjusted Hazard Ratio [aHR], 95% CI: 0.86, 95% CI: 0.79 to 0.93), hemorrhagic stroke (aHR: 0.51, 0.40 to 0.65), and acute myocardial infarction (aHR: 0.88, 95% CI: 0.77 to 0.99), and no relation was seen between dabigatran and the composite harm outcome (aHR: 0.94, 95% CI: 0.87 to 1.01). However, dabigatran was associated with a higher risk of gastrointestinal bleeding (aHR: 1.11, 95% CI: 1.02 to 1.22). Estimates of effectiveness and safety appeared to be mostly similar across subgroups. Conclusions Dabigatran could be a safe and potentially more effective alternative to warfarin in patients with atrial fibrillation managed in routine practice settings. PMID:25862791

[Management of new oral anticoagulants in gastrointestinal bleeding and endoscopy].

PubMed

del Molino, Fátima; Gonzalez, Isabel; Saperas, Esteve

2015-10-01

New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

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.

Trends in initiation of direct oral anticoagulant therapies for atrial fibrillation in a national population-based cross-sectional study in the French health insurance databases

PubMed Central

Huiart, Laetitia; Ferdynus, Cyril; Renoux, Christel; Beaugrand, Amélie; Lafarge, Sophie; Bruneau, Léa; Suissa, Samy; Maillard, Olivier; Ranouil, Xavier

2018-01-01

Objective Unlike several other national health agencies, French health authorities recommended that the newer direct oral anticoagulant (DOAC) agents only be prescribed as second choice for the treatment of newly diagnosed non-valvular atrial fibrillation (NVAF), with vitamin K antagonists (VKA) remaining the first choice. We investigated the patterns of use of DOACs versus VKA in the treatment of NVAF in France over the first 5 years of DOAC availability. We also identified the changes in patient characteristics of those who initiated DOAC treatment over this time period. Methods Based on the French National Health Administrative Database, we constituted a population-based cohort of all patients who were newly treated for NVAF between January 2011 and December 2015. Trends in drug use were described as the percentage of patients initiating each drug at the time of treatment initiation. A multivariate analysis using logistic regression model was performed to identify independent sociodemographic and clinical predictors of initial anticoagulant choice. Results The cohort comprised 814 446 patients who had received a new anticoagulant treatment for NVAF. The proportion of patients using DOACs as initial anticoagulant therapy reached 54% 3 months after the Health Ministry approved the reimbursement of dabigatran for NVAF, and 61% by the end of 2015, versus VKA use. In the multivariate analysis, we found that DOAC initiators were younger and healthier overall than VKA initiators, and this tendency was reinforced over the 2011–2014 period. DOACs were more frequently prescribed by cardiologists in 2012 and after (adjusted OR in 2012: 2.47; 95% CI 2.40 to 2.54). Conclusion Despite recommendations from health authorities, DOACs have been rapidly and massively adopted as initial therapy for NVAF in France. Observational studies should account for the fact that patients selected to initiate DOAC treatment are healthier overall, as failure to do so may bias the risk–benefit assessment of DOACs. PMID:29602837

Assessment of Degree of Anticoagulation Control in Patients With Atrial Fibrillation in Primary Health Care in Galicia, Spain: ANFAGAL Study.

PubMed

Cinza-Sanjurjo, Sergio; Rey-Aldana, Daniel; Gestal-Pereira, Enrique; Calvo-Gómez, Carlos

2015-09-01

To determine the degree of control of patients on anticoagulants in follow-up in primary care in Galicia and investigate whether time in therapeutic range as estimated using the number of acceptable controls is comparable with the estimation using the Rosendaal method. Transversal study that included patients older than 65 years, diagnosed with nonvalvular atrial fibrillation, on anticoagulants for at least 1 year. Control was considered good when the time in therapeutic range was greater than 65%, estimated by the Rosendaal method, or 60% estimated by the number of acceptable controls. We enrolled 511 patients (53.0% women; mean [standard deviation] age, 77.8 [0.6] years). Overall, 41.5% of the patients were in therapeutic range at fewer than 60% of the controls and 42.7% spent less than 65% of follow-up in therapeutic range, as estimated with the Rosendaal method. In the group of patients with poor control, we observed more drugs (6.8 [0.4] vs 5.7 [0.3]; P<.0001), greater presence of kidney disease (24.3% vs 17.0%; P=.05), and higher HAS-BLED scores (3.8 [0.1] vs 2.5 [0.1]; P<.0001). The cutoff of 60% for number of acceptable controls had a sensitivity and specificity of 79.4% and 86.7%, respectively, with an area under the curve of 0.92 (95%CI, 0.87-0.97). More than 40% of patients on anticoagulants do not reach the minimum time in therapeutic range to benefit from anticoagulation. The factors associated with worse control were kidney disease and high risk of cerebral hemorrhage. The 2 methods of estimation are comparable. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Exploratory Network Meta Regression Analysis of Stroke Prevention in Atrial Fibrillation Fails to Identify Any Interactions with Treatment Effect.

PubMed

Batson, Sarah; Sutton, Alex; Abrams, Keith

2016-01-01

Patients with atrial fibrillation are at a greater risk of stroke and therefore the main goal for treatment of patients with atrial fibrillation is to prevent stroke from occurring. There are a number of different stroke prevention treatments available to include warfarin and novel oral anticoagulants. Previous network meta-analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation acknowledge the limitation of heterogeneity across the included trials but have not explored the impact of potentially important treatment modifying covariates. To explore potentially important treatment modifying covariates using network meta-regression analyses for stroke prevention in atrial fibrillation. We performed a network meta-analysis for the outcome of ischaemic stroke and conducted an exploratory regression analysis considering potentially important treatment modifying covariates. These covariates included the proportion of patients with a previous stroke, proportion of males, mean age, the duration of study follow-up and the patients underlying risk of ischaemic stroke. None of the covariates explored impacted relative treatment effects relative to placebo. Notably, the exploration of 'study follow-up' as a covariate supported the assumption that difference in trial durations is unimportant in this indication despite the variation across trials in the network. This study is limited by the quantity of data available. Further investigation is warranted, and, as justifying further trials may be difficult, it would be desirable to obtain individual patient level data (IPD) to facilitate an effort to relate treatment effects to IPD covariates in order to investigate heterogeneity. Observational data could also be examined to establish if there are potential trends elsewhere. The approach and methods presented have potentially wide applications within any indication as to highlight the potential benefit of extending decision problems to include additional comparators outside of those of primary interest to allow for the exploration of heterogeneity.

Posttraumatic gastric wall hematoma in a patient under anticoagulant therapy. Case report and literature review.

PubMed

Mânzat Saplacan, Roberta Maria; Catinean, Adrian; Manole, Simona; Valean, Simona Doina; Chira, Romeo Ioan; Mircea, Petru Adrian

2011-06-01

We report the clinical observation of a 58-year old patient who presented with upper abdominal pain and a small ecchymosis located in the umbilical area. Personal history of the patient revealed ischemic heart disease and chronic atrial fibrillation. He was under treatment with oral anticoagulants (coumarins). The clinical data and especially the imaging investigations led to a diagnosis of gastric wall hematoma, possibly occurring post-traumatically in a patient under anticoagulant treatment. A conservative therapeutic approach was adopted and ultrasound surveillance. After 6 months the gastric parietal collection manifested complete resorption, spontaneously. In relation to the case presentation, we also discuss some issues on the frequency, diagnosis and therapeutic attitude in this rare complication of anticoagulant therapy.

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.

Discontinuation risk comparison among 'real-world' newly anticoagulated atrial fibrillation patients: Apixaban, warfarin, dabigatran, or rivaroxaban.

PubMed

Lip, Gregory Y H; Pan, Xianying; Kamble, Shital; Kawabata, Hugh; Mardekian, Jack; Masseria, Cristina; Phatak, Hemant

2018-01-01

Discontinuation of oral anticoagulants may expose non-valvular atrial fibrillation (NVAF) patients to an increased risk of stroke. This study describes the real-world discontinuation rates and compared the risk of drug discontinuation among NVAF patients initiating apixaban, warfarin, dabigatran, or rivaroxaban. This retrospective cohort study evaluated newly-anticoagulated NVAF patients in the MarketScan® data population from 01/01/2012 through 12/31/2014. Discontinuation was defined as a lack of subsequent prescription of the index drug within 30 days after the last supply day of the last prescription. A Cox model was used to estimate the hazard ratio (HR) of discontinuation, adjusted for age, sex, and comorbidities. Among 45,361 eligible NVAF patients, 15,461 (34.1%) initiated warfarin; 7,438 (16.4%) apixaban; 4,661 (10.3%) dabigatran; and 17,801 (39.2%) initiated rivaroxaban treatment. Compared to warfarin, patients who initiated dabigatran (adjusted HR [aHR]: 0.84, 95% confidence interval [CI]: 0.80-0.87, P<0.001), rivaroxaban (aHR: 0.70, 95% CI: 0.68-0.73, P<0.001), or apixaban (aHR: 0.57, 95% CI: 0.55-0.60, P<0.001) were 16%, 30%, and 43% less likely to discontinue treatment, respectively. When compared to apixaban, patients who initiated dabigatran (aHR: 1.46, 95% CI: 1.38-1.54, P<0.001) or rivaroxaban (aHR: 1.23, 95% CI: 1.17-1.28, P<0.001) were more likely to discontinue treatment. Among newly-anticoagulated NVAF patients in the real-world setting, initiation on rivaroxaban, dabigatran, or apixaban was associated with a significantly lower risk of discontinuation compared to warfarin. When compared to apixaban, patients who initiated treatment with warfarin, dabigatran, or rivaroxaban were more likely to discontinue treatment.

Use and Outcomes of Antiarrhythmic Therapy in Patients with Atrial Fibrillation Receiving Oral Anticoagulation: Results from the ROCKET AF Trial

PubMed Central

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

2014-01-01

Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235

Antithrombotic Therapy for Atrial Fibrillation

PubMed Central

You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.

2012-01-01

Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach. PMID:22315271

[Recurrent right atrial thrombus in a patient with atrial fibrillation and heart failure].

PubMed

Elikowski, Waldemar; Wróblewski, Dariusz; Małek-Elikowska, Małgorzata; Mazurek, Andrzej; Foremska-Iciek, Joanna; Łazowski, Stanisław

2015-11-01

Atrial fibrillation and heart failure are factors predisposing to locally formed intracardiac thrombosis, which is usually localized in left-sided chambers. A case report. The authors present a case of a 50-year-old male with permanent atrial fibrillation and dilated cardiomyopathy in whom recurrent right atrial thrombus was observed. Initially, the lesion was detected in echocardiography while he was hospitalized due to extensive right-sided pneumonia. The thrombus was successfully treated with heparin, followed by warfarin. Even though the patient continued warfarin use properly, there was recurrence of the thrombus two years later during a new episode of heart failure exacerbation. Because the thrombus was resistant to intensified anticoagulation, cardiac surgery was needed. A large (30 x 25 mm) pedunculated thrombus, as well as two smaller ones (each of 10 x 10 mm) attached closely to the atrial wall and previously not detected either by echocardiography or by magnetic resonance imaging, were excited. A partially organized pattern of the thrombi in histological examination can explain lack of anticoagulation effectiveness. © 2015 MEDPRESS.

Oral Anticoagulation in Patients With Liver Disease.

PubMed

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Upsetting the apple cart: a community anticoagulation clinic survey of life event factors that undermine safe therapy.

PubMed

Edmundson, Sarah; Stuenkel, Diane L; Connolly, Phyllis M

2005-09-01

Anticoagulation therapy is a life-enhancing therapy for patients who are at risk for embolic events secondary to atrial fibrillation, valve replacement, and other comorbidities. Clinicians are motivated to decrease the amount of time that patients are either under- or over-anticoagulated, common conditions that decrease patient safety at either extreme. The primary purpose of this descriptive study was to examine the relationship between personal life event factors as measured by Norbeck's Life Events Questionnaire, core demographics such as age and income, and anticoagulation regulation. Although many factors affect anticoagulation therapy, the precise impact of life events, positive or negative, is unknown. The salient findings of this study (n = 202) showed a small, though statistically significant, inverse relationship (r = -0.184, P < .01) between negative life events and decreased time within therapeutic international normalized ratio. Total Life Event scores showed a statistically significant inverse relationship (r = -0.159, P < .05) to international normalized ratio time within therapeutic level. Lower income was inversely associated with higher negative Life Event scores (r = -0.192, P < .01). The findings demonstrate the need for strategies that address the potential impact of life events in conjunction with coexisting screening measures used in anticoagulation clinics. Implications for this study are limited by lack of methodology documenting concurrent social support factors and limitations of the research tool to reflect life event issues specific to outpatient seniors.

[Anticoagulation in the aged patient with atrial fibrillation: What are prescribing cardiologists, geriatricians and general practitioners?].

PubMed

Fuchs, P; Vogel, T; Lang, P-O

2015-08-01

To assess prescribing of anticoagulants in atrial fibrillation (AF) in the elderly, both a quantitative point of view (rate of anticoagulation) and qualitative (type of anticoagulation). Determinants of prescribing and non-prescribing were also analysed. Prospective survey of practice, based on one clinical case and questionnaire conducted in 60 practitioners (20 cardiologists [C], 20 geriatricians [G] and 20 general practitioners [GP]). In reading the clinical case, 88.3% of physicians would have initiated a treatment; three types of treatments would have been chosen: AVK (68.3%), ODA (20.0%) and platelet antiaggregant (11.7%). Criteria taken into account to initiate anticoagulation varied according to the specialty. Cardiologists considered more the age criteria (C: 95.0%, G: 75.0%, MG: 60.0%; P<0.05), diabetes (C: 90.0%, G: 60.0%, MG: 55.0%; P<0.05), hypertension (C: 85.0%, G: 55.0%, MG: 60.0%; P<0.05) and female gender (C: 80.0%, G: 35.0%, MG: 25.0%; P<0.05). The quality of renal function was however a more secondary criteria (C: 15.0%, G: 5.0%, MG: 0.0%; P<0.05). General practitioners considered most frequently the presence of underlying heart disease (C: 35.0%, G: 5.0%, MG: 45.0%; P<0.05) as well as usual cardiovascular risk factors (overweight, dyslipidaemia; P<0.05). Risk of bleeding, however, was observed by 76.7% of physicians in the clinical situation presented (C: 70.0%, G: 75.0%, MG: 85.0%; P<0.05). This survey confirms that the FA remains under anticoagulated in the elderly and the barriers to the prescription of oral anticoagulation are often without rational basis. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries.

PubMed

Steinberg, Benjamin A; Gao, Haiyan; Shrader, Peter; Pieper, Karen; Thomas, Laine; Camm, A John; Ezekowitz, Michael D; Fonarow, Gregg C; Gersh, Bernard J; Goldhaber, Samuel; Haas, Sylvia; Hacke, Werner; Kowey, Peter R; Ansell, Jack; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Turpie, Alexander; Verheugt, Freek; Piccini, Jonathan P; Kakkar, Ajay; Peterson, Eric D; Fox, Keith A A

2017-12-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment. Demographics, comorbidities, and stroke risk of the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF II (n=11,602) registries were compared (overall N=73,004 from 35 countries). Stroke prevention therapies were assessed among patients with new-onset AF (≤6 weeks). Patients from GARFIELD-AF were less likely to be white (63% vs 89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19% vs 36% and 27%), but had similar stroke risk (85% CHA 2 DS 2 -VASc ≥2 vs 91% and 85%) and lower bleeding risk (11% with HAS-BLED ≥3 vs 24% and 15%). Oral anticoagulant use was 46% and 57% for patients with a CHA 2 DS 2 -VASc=0 and 69% and 87% for CHA 2 DS 2 -VASc ≥2 in GARFIELD-AF and ORBIT-AF II, respectively, but with substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93% [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non-vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016 for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II). Among new-onset AF patients, non-vitamin K antagonist oral anticoagulant use has increased and antiplatelet monotherapy has decreased. However, anticoagulation is used frequently in low-risk patients and inconsistently in those at high risk of stroke. Significant geographic variability in anticoagulation persists and represents an opportunity for improvement. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin: a "real-world" observational study in the United States.

PubMed

Lip, Gregory Y H; Pan, Xianying; Kamble, Shital; Kawabata, Hugh; Mardekian, Jack; Masseria, Cristina; Bruno, Amanda; Phatak, Hemant

2016-09-01

Limited data are available about the real-world safety of non-vitamin K antagonist oral anticoagulants (NOACs). To compare the major bleeding risk among newly anticoagulated non-valvular atrial fibrillation (NVAF) patients initiating apixaban, warfarin, dabigatran or rivaroxaban in the United States. A retrospective cohort study was conducted to compare the major bleeding risk among newly anticoagulated NVAF patients initiating warfarin, apixaban, dabigatran or rivaroxaban. The study used the Truven MarketScan(®) Commercial & Medicare supplemental US database from 1 January 2013 through 31 December 2013. Major bleeding was defined as bleeding requiring hospitalisation. Cox model estimated hazard ratios (HRs) of major bleeding were adjusted for age, gender, baseline comorbidities and co-medications. Among 29 338 newly anticoagulated NVAF patients, 2402 (8.19%) were on apixaban; 4173 (14.22%) on dabigatran; 10 050 (34.26%) on rivaroxaban; and 12 713 (43.33%) on warfarin. After adjusting for baseline characteristics, initiation on warfarin [adjusted HR (aHR): 1.93, 95% confidence interval (CI): 1.12-3.33, P=.018] or rivaroxaban (aHR: 2.19, 95% CI: 1.26-3.79, P=.005) had significantly greater risk of major bleeding vs apixaban. Dabigatran initiation (aHR: 1.71, 95% CI: 0.94-3.10, P=.079) had a non-significant major bleeding risk vs apixaban. When compared with warfarin, apixaban (aHR: 0.52, 95% CI: 0.30-0.89, P=.018) had significantly lower major bleeding risk. Patients initiating rivaroxaban (aHR: 1.13, 95% CI: 0.91-1.41, P=.262) or dabigatran (aHR: 0.88, 95% CI: 0.64-1.21, P=.446) had a non-significant major bleeding risk vs warfarin. Among newly anticoagulated NVAF patients in the real-world setting, initiation with rivaroxaban or warfarin was associated with a significantly greater risk of major bleeding compared with initiation on apixaban. When compared with warfarin, initiation with apixaban was associated with significantly lower risk of major bleeding. Additional observational studies are required to confirm these findings. © 2016 The Authors International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

Clinical considerations on the posology of direct oral anticoagulants.

PubMed

Sáez-Peñataro, J; Avendaño-Solá, C; González-Juanatey, J R

2016-10-01

The efficacy of dicoumarin anticoagulants has been shown in patients with nonvalvular atrial fibrillation. However, they have drawbacks such as the need to adjust the dosage and the interaction with drugs and food. Direct oral anticoagulants are an effective and safe alternative and have a less complicated clinical management. There is considerable debate on the selection criteria for the posology regimens of direct oral anticoagulants. The differences among them and their administration regimens have raised questions about the clinical, pharmacokinetic and pharmacodynamic selection criteria that support the posology. This review critically analyses the available evidence and its impact on the final selection of the dosage regimen. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Evaluation of bleeding in patients receiving direct oral anticoagulants

PubMed Central

Hellenbart, Erika L; Faulkenberg, Kathleen D; Finks, Shannon W

2017-01-01

Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants. PMID:28860793

Does periprocedural anticoagulation management of atrial fibrillation affect the prevalence of silent thromboembolic lesion detected by diffusion cerebral magnetic resonance imaging in patients undergoing radiofrequency atrial fibrillation ablation with open irrigated catheters? Results from a prospective multicenter study.

PubMed

Di Biase, Luigi; Gaita, Fiorenzo; Toso, Elisabetta; Santangeli, Pasquale; Mohanty, Prasant; Rutledge, Neal; Yan, Xue; Mohanty, Sanghamitra; Trivedi, Chintan; Bai, Rong; Price, Justin; Horton, Rodney; Gallinghouse, G Joseph; Beheiry, Salwa; Zagrodzky, Jason; Canby, Robert; Leclercq, Jean François; Halimi, Franck; Scaglione, Marco; Cesarani, Federico; Faletti, Riccardo; Sanchez, Javier; Burkhardt, J David; Natale, Andrea

2014-05-01

Silent cerebral ischemia (SCI) has been reported in 14% of cases after catheter ablation of atrial fibrillation (AF) with radiofrequency (RF) energy and discontinuation of warfarin before AF ablation procedures. The purpose of this study was to determine whether periprocedural anticoagulation management affects the incidence of SCI after RF ablation using an open irrigated catheter. Consecutive patients undergoing RF ablation for AF without warfarin discontinuation and receiving heparin bolus before transseptal catheterization (group I, n = 146) were compared with a group of patients who had protocol deviation in terms of maintaining the therapeutic preprocedural international normalized ratio (patients with subtherapeutic INR) and/or failure to receive pretransseptal heparin bolus infusion and/or ≥2 consecutive ACT measurements <300 seconds (noncompliant population, group II, n = 134) and with a group of patients undergoing RF ablation with warfarin discontinuation bridged with low molecular weight heparin (group III, n = 148). All patients underwent preablation and postablation (within 48 hours) diffusion magnetic resonance imaging. SCI was detected in 2% of patients (3/146) in group I, 7% (10/134) in group II, and 14% (21/148) in group III (P <.001). "Therapeutic INR" was strongly associated with a lower prevalence of postprocedural silent cerebral ischemia (SCI). Multivariable analysis demonstrated nonparoxysmal AF (odds ratio 3.8, 95% confidence interval 1.5-9.7, P = .005) and noncompliance to protocol (odds ratio 2.8, 95% confidence interval 1.5-5.1, P <.001] to be significant predictors of ischemic events. Strict adherence to an anticoagulation protocol significantly reduces the prevalence of SCI after catheter ablation of AF with RF energy. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Mobile Health Technology for Atrial Fibrillation Management Integrating Decision Support, Education, and Patient Involvement: mAF App Trial.

PubMed

Guo, Yutao; Chen, Yundai; Lane, Deirdre A; Liu, Lihong; Wang, Yutang; Lip, Gregory Y H

2017-12-01

Mobile Health technology for the management of patients with atrial fibrillation is unknown. The simple mobile AF (mAF) App was designed to incorporate clinical decision-support tools (CHA 2 DS 2 -VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes Mellitus, Prior Stroke or TIA, Vascular disease, Age 65-74 years, Sex category], HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly], SAMe-TT 2 R 2 [Sex, Age <60 years, Medical history, Treatment, Tobacco use, Race] scores), educational materials, and patient involvement strategies with self-care protocols and structured follow-up. Patients with atrial fibrillation were randomized into 2 groups (mAF App vs usual care) in a cluster randomized design pilot study. Patients' knowledge, quality of life, drug adherence, and anticoagulation satisfaction were evaluated at baseline, 1 month, and 3 months. Usability, feasibility, and acceptability of the mAF App were assessed at 1 month. A total of 113 patients were randomized to mAF App intervention (mean age, 67.4 years; 57.5% were male; mean follow-up, 69 days), and 96 patients were randomized to usual care (mean age, 70.9 years; 55.2% were male; mean follow-up, 95 days). More than 90% of patients reported that the mAF App was easy, user-friendly, helpful, and associated with significant improvements in knowledge compared with the usual care arm (P values for trend <.05). Drug adherence and anticoagulant satisfaction were significantly better with the mAF App versus usual care (all P < .05). Quality of life scores were significantly increased in the mAF App arm versus usual care, with anxiety and depression reduced (all P < .05). The pilot mAFA Trial is the first prospective randomized trial of Mobile Health technology in patients with atrial fibrillation, demonstrating that the mAF App, integrating clinical decision support, education, and patient-involvement strategies, significantly improved knowledge, drug adherence, quality of life, and anticoagulation satisfaction. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical Outcomes and History of Fall in Patients with Atrial Fibrillation Treated with Oral Anticoagulation: Insights From the ARISTOTLE Trial.

PubMed

Rao, Meena P; Vinereanu, Dragos; Wojdyla, Daniel M; Alexander, John H; Atar, Dan; Hylek, Elaine M; Hanna, Michael; Wallentin, Lars; Lopes, Renato D; Gersh, Bernard J; Granger, Christopher B

2018-03-01

We assessed outcomes among anticoagulated patients with atrial fibrillation and a history of falling, and whether the benefits of apixaban vs warfarin are consistent in this population. Of the 18,201 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, 16,491 had information about history of falling-753 with history of falling and 15,738 without history of falling. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding. When compared with patients without a history of falling, patients with a history of falling were older, more likely to be female and to have dementia, cerebrovascular disease, depression, diabetes, heart failure, osteoporosis, fractures, and higher CHA 2 DS 2 -VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or TIA or thromboembolism, Vascular disease, Age 65-74 years, Sex category female) and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratio, Elderly, Drugs or alcohol) scores. Patients with a history of falling had higher rates of major bleeding (adjusted hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.05-1.84; P = .020), including intracranial bleeding (adjusted HR 1.87; 95% CI, 1.02-3.43; P = .044) and death (adjusted HR 1.70; 95% CI, 1.36-2.14; P < .0001), but similar rates of stroke or systemic embolism and hemorrhagic stroke. There was no evidence of a differential effect of apixaban compared with warfarin on any outcome, regardless of history of falling. Among those with a history of falling, subdural bleeding occurred in 5 of 367 patients treated with warfarin and 0 of 386 treated with apixaban. Patients with atrial fibrillation and a history of falling receiving anticoagulation have a higher risk of major bleeding, including intracranial, and death. The efficacy and safety of apixaban compared with warfarin were consistent, irrespective of history of falling. Copyright © 2018 Elsevier Inc. All rights reserved.

Use of Oral Anticoagulant Therapy in Older Adults with Atrial Fibrillation after Acute Ischemic Stroke

PubMed Central

McGrath, Emer R.; Go, Alan S.; Chang, Yuchiao; Borowsky, Leila H.; Fang, Margaret C.; Reynolds, Kristi; Singer, Daniel E.

2016-01-01

Objective To explore barriers to anticoagulation among older atrial fibrillation (AF) patients at high risk for stroke and identify opportunities where interventions might increase use of oral anticoagulants (OAC). Design Retrospective cohort study Setting Two large community-based AF cohorts Participants 1405 patients (mean age 79 years) with ischemic stroke surviving hospitalization. Measurements Using structured chart review, we identified reasons for non-use of OACand assessed one-year post-stroke survival. Logistic regression identified correlates of OAC non-use. Results The median CHA2DS2-VASc score was 5, yet 44% of patients were not prescribed OAC at discharge. The most frequent (non-mutually exclusive) physician reasons for non-prescription of OAC included fall risk (26.7%), poor prognosis (19.3%), bleeding history (17.1%), patient/family refusal (14.9%), older age (11.0%) and dementia (9.4%). Older age (OR 8.96, 95% CI 5.01–16.04 for age ≥85 vs. age <65 years) and increased disability (OR 12.58, 95% CI 5.82–27.21 for severe vs. no deficit) were the most important independent predictors of non-use of OAC. By one year, 42.5% of those not receiving OAC at discharge had died versus 19.1% of those receiving OAC (p<0.0001), far higher than recurrent stroke rates. Conclusion Despite very high stroke risk, over 40% of patients were not discharged on OAC. Dominant reasons included fall risk, poor prognosis, older age, and dementia. These patients’ elevated 1-year mortality rate confirmed their high level of comorbidity. Future work to improve outcomes and clinical decisions regarding anticoagulation in this patient population should focus on: mitigation of fall risk, better assessment and decision tools for determining risk/benefit in individual patients, and determining whether newer anticoagulants are safer in complex elderly and/or frail patients. PMID:28039855

Setting priorities in the health care sector - the case of oral anticoagulants in nonvalvular atrial fibrillation in Denmark.

PubMed

Poulsen, Peter Bo; Johnsen, Søren Paaske; Hansen, Morten Lock; Brandes, Axel; Husted, Steen; Harboe, Louise; Dybro, Lars

2017-01-01

Resources devoted to health care are limited, therefore setting priorities is required. It differs between countries whether decision-making concerning health care technologies focus on broad economic perspectives or whether focus is narrow on single budgets ("silo mentality"). The cost perspective as one part of the full health economic analysis is important for decision-making. With the case of oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF), the aim is to discuss the implication of the use of different cost perspectives for decision-making and priority setting. In a cost analysis, the annual average total costs of five oral anticoagulants (warfarin and non-vitamin K oral anticoagulants [NOACs; dabigatran, rivaroxaban, apixaban, and edoxaban]) used in daily clinical practice in Denmark for the prevention of stroke in NVAF patients are analyzed. This is done in pairwise comparisons between warfarin and each NOAC based on five potential cost perspectives, from a "drug cost only" perspective up to a "societal" perspective. All comparisons of warfarin and NOACs show that the cost perspective based on all relevant costs, ie, total costs perspective, is essential for the choice of therapy. Focusing on the reimbursement costs of the drugs only, warfarin is the least costly option. However, with the aim of therapy to prevent strokes and limit bleedings, including the economic impact of this, all NOACs, except rivaroxaban, result in slightly lower health care costs compared with warfarin. The same picture was found applying the societal perspective. Many broad cost-effectiveness analyses of NOACs exist. However, in countries with budget focus in decision-making this information does not apply. The present study's case of oral anticoagulants has shown that decision-making should be based on health care or societal cost perspectives for optimal use of limited resources. Otherwise, the risk is that suboptimal decisions will be likely.

Performance of the "CCS Algorithm" in real world patients.

PubMed

LaHaye, Stephen A; Olesen, Jonas B; Lacombe, Shawn P

2015-06-01

With the publication of the 2014 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation, the Canadian Cardiovascular Society Atrial Fibrillation Guidelines Committee has introduced a new triage and management algorithm; the so-called "CCS Algorithm". The CCS Algorithm is based upon expert opinion of the best available evidence; however, the CCS Algorithm has not yet been validated. Accordingly, the purpose of this study is to evaluate the performance of the CCS Algorithm in a cohort of real world patients. We compared the CCS Algorithm with the European Society of Cardiology (ESC) Algorithm in 172 hospital inpatients who are at risk of stroke due to non-valvular atrial fibrillation in whom anticoagulant therapy was being considered. The CCS Algorithm and the ESC Algorithm were concordant in 170/172 patients (99% of the time). There were two patients (1%) with vascular disease, but no other thromboembolic risk factors, which were classified as requiring oral anticoagulant therapy using the ESC Algorithm, but for whom ASA was recommended by the CCS Algorithm. The CCS Algorithm appears to be unnecessarily complicated in so far as it does not appear to provide any additional discriminatory value above and beyond the use of the ESC Algorithm, and its use could result in under treatment of patients, specifically female patients with vascular disease, whose real risk of stroke has been understated by the Guidelines.

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

Standards of care issues with anticoagulation in real-world populations.

PubMed

2015-01-01

Current guidelines recommend anticoagulants for reducing the risk of stroke in appropriate patients with nonvalvular atrial fibrillation (NVAF) and for the acute treatment of venous thromboembolism (VTE) and the prevention of recurrent VTE. Warfarin is the standard of care for both NVAF and VTE, yet International Normalized Ratio (INR) control remains suboptimal, even in the clinical trial setting. Maintaining INR within the recommended therapeutic range is associated with better outcomes in these distinct populations. In VTE, high rates of recurrence have been reported during the first few weeks of treatment, emphasizing the importance of surveillance during this time and of early optimization of anticoagulation therapy. The NVAF population tends to have more comorbidities and requires longer-term therapy. It is important to keep in mind that real-world patient populations are more complex than those in controlled studies. Patients with multiple comorbidities are particularly challenging, and physicians may focus on clinically urgent issues rather than anticoagulation optimization. Despite the many complexities associated with the use of warfarin, it remains a mainstay of anticoagulation therapy. Aligning financial incentives and improving care coordination are important factors in moving toward better outcomes for patients who need anticoagulation therapy. The increased focus on value-based care and evolving approaches to patient treatment could lead more physicians and payers to consider alternatives to warfarin, including the use of novel oral anticoagulants.

[Analysis on long-term compliance of anticoagulation treatment and demands of disease management in patients with atrial fibrillation].

PubMed

Zuo, Hui-juan; Su, Jiang-lian; Lin, Yun; Zeng, Zhe-chun; Wang, Jin-wen

2010-08-24

To analyze the long-term compliance of oral anticoagulant therapy and the demands of disease management in patient with atrial fibrillation (AF). Inpatients with AF taking warfarin were collected from Department of Internal Medicine from January 1 to December 31, 2008. Inpatients from departments of surgery, ophthalmology, otorhinolaryngology, dermatology and pediatrics and those on a previous warfarin therapy were excluded. The data of patient profiles, medical history and anticoagulant treatment were collected from electronic medical record. And the status of anticoagulant treatment one year later and demands of disease management were inquired by telephone. A total of 268 AF patients received a telephone survey. Among them, 145 patients (54.1%) continued taking warfarin. Gender, age, type of AF, duration of AF and history of ischemic stroke was not significantly associated with the compliance of anticoagulant treatment. The odds ratio was 1.74 (95%CI: 0.67-4.47), 0.87 (95%CI: 0.30-2.53), 1.59 (95%CI: 0.35-1.09), 1.09 (95%CI: 0.61-1.93) and 0.44 (95%CI: 0.12-1.60) respectively. Among patients on warfarin, INR was monitored monthly in 88 patients (60.7%) and 70 patients (48.3%) had an INR value of 2.0-3.0. Among 123 withdrawal patients, 88 patients (71.5%) terminated treatment within 6 month. The common reasons included patient ignorance about long-term anticoagulant treatment (35.0%) and switching to aspirin because of a poor effect (24.4%). About 80% of patients wished to obtain instructions about INR monitoring and adjustment of drug dosage. Among them, 196/268 patients (73.1%) wished for a regular follow-up. And 176/196 patients (89.8%) opted for a telephone follow-up and 150/176 patients (85.2%) wanted to receive monthly instructions. The compliance of anticoagulation treatment and the target-meeting proportion of INR value are relative low. And the common reasons of withdrawal are patient ignorance about long-term anticoagulant treatment and switching to aspirin because of a poor effect. Disease management will meet most of AF patients' demands.

Management of Major Bleeding in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants Compared With Warfarin in Clinical Practice (from Phase II of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF II]).

PubMed

Steinberg, Benjamin A; Simon, DaJuanicia N; Thomas, Laine; Ansell, Jack; Fonarow, Gregg C; Gersh, Bernard J; Kowey, Peter R; Mahaffey, Kenneth W; Peterson, Eric D; Piccini, Jonathan P

2017-05-15

Non-vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry, we analyzed rates of International Society on Thrombosis and Haemostasis major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total, 344 patients with atrial fibrillation experienced major bleeding events over a median follow-up of 360 days follow-up: n = 273 on NOAC (3.3 per 100 patient-years) and n = 71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p = 0.5), as was gastrointestinal bleeding (1.8 for NOAC vs 1.3 for warfarin, p = 0.1). Blood products and correction agents were less commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs 76%, p = 0.0004 for blood products; 0% vs 1.5% for recombinant factor; p = 0.0499); no patients received pharmacologic hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 NOAC-treated patients (8.4%) died versus 5 (7.0%) on warfarin (p = 0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Contemporary Atrial Fibrillation Management: A Comparison of the Current AHA/ACC/HRS, CCS, and ESC Guidelines.

PubMed

Andrade, Jason G; Macle, Laurent; Nattel, Stanley; Verma, Atul; Cairns, John

2017-08-01

In this article we compare and contrast the current recommendations, and highlight the important differences, in the American College of Cardiology/American Heart Association/Heart Rhythm Society, European Society of Cardiology, and Canadian Cardiovascular Society atrial fibrillation (AF) guidelines. Although many of the recommendations of the various societies are similar, there are important differences in the methodologies underlying their development and the specific content. Specifically, key differences can be observed in: (1) the definition of nonvalvular AF, which subsequently affects anticoagulation choices and candidacy for non-vitamin K antagonist oral anticoagulants; (2) the symptom score used to guide management decisions and longitudinal patient profiling; (3) the stroke risk stratification algorithm used to determine indications for oral anticoagulant therapy; (4) the role of acetylsalicylic acid in stroke prevention in AF; (5) the antithrombotic regimens used in the context of coronary artery disease, acute coronary syndromes, and percutaneous coronary intervention; (6) the rate control target and medications recommended to achieve the target; and (7) the role of "first-line" catheter ablation, open surgical ablation, and left atrial appendage exclusion. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Recommendations for the use of new oral anticoagulants (NOACs) after TIA or stroke caused by atrial fibrillation (AF), after a consensus conference among Italian neurologists (the Venice group).

PubMed

Toso, Vito

2014-05-01

Vascular neurologists of Veneto and Friuli Venezia Giulia, north-east regions of Italy, have sought an agreement on the two following questions: (A) what prophylactic treatment should we recommend to patients with a stroke ascribed to atrial fibrillation (AF), who were not previously on antithrombotic treatment, to prevent further strokes? (B) What should we do in the event of an ischemic or hemorrhagic stroke associated with AF in patients who were already on antithrombotic treatment? There was a unanimous consensus for preferring the new oral anticoagulants (NOACs) in patients not taking any antithrombotics and in cases treated with antithrombotic drugs (coumadin and/or antiplatelets), due to a lower incidence of intracranial bleeding complications and a noninferiority for recurrent stroke or TIA. Even after intracranial bleeding complications, when it is useful or necessary to continue anticoagulant treatment, the group of experts preferred the NOACs, suggesting, however, to be very cautious in cases with widespread leukoaraiosis or microbleeds, practice frequent monitoring of creatinine clearance (CrCl) and avoid using NOACs when CrCl is <30 mL/min.

Atrial Fibrillation Patients Treated With Long-Term Warfarin Anticoagulation Have Higher Rates of All Dementia Types Compared With Patients Receiving Long-Term Warfarin for Other Indications.

PubMed

Bunch, T Jared; May, Heidi T; Bair, Tami L; Crandall, Brian G; Cutler, Michael J; Day, John D; Jacobs, Victoria; Mallender, Charles; Osborn, Jeffrey S; Stevens, Scott M; Weiss, J Peter; Woller, Scott C

2016-07-11

The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. We previously found a significantly increased risk of dementia in AF patients taking warfarin with a low percentage of time in therapeutic range. The purpose of this study was to determine the extent to which AF itself increases dementia risk, in addition to long-term anticoagulation exposure. A total of 10 537 patients anticoagulated with warfarin (target INR 2-3), managed by the Clinical Pharmacist Anticoagulation Service with no history of dementia were included. Warfarin indication was for AF (n=4460), thromboembolism (n=5868), and mechanical heart valve(s) (n=209). Patients in the latter 2 categories were included only if they had no prior history of AF. The primary outcome was dementia. Patients with AF were older and had higher rates of hypertension, diabetes, heart failure, and stroke. AF patients experienced higher rates of total dementia (5.8% versus 1.6%, P<0.0001), Alzheimer disease (2.8% versus 0.9%, P<0.0001), and vascular dementia (1.0% versus 0.2%, P<0.0001). A propensity analysis of 6030 patients was performed to account for baseline demographics differences. Long-term risk of dementia remained significant in AF patients compared with matched non-AF patients (total dementia: hazard ratio [HR]=2.42 [1.85-3.18], P<0.0001; Alzheimer: HR=2.04 [1.40-2.98], P<0.0001; senile: HR=2.46 [1.58-3.86], P<0.0001). Low percent therapeutic range compared with a higher percent therapeutic range was associated with dementia risk in both AF (26-50% versus >75%: HR=2.51, P=0.005) and non-AF groups (≤25% versus >75%: HR=3.92, P<0.0001). The presence of AF significantly increases risk of dementia, including Alzheimer's disease, compared with matched patients receiving warfarin anticoagulation for other reasons. Quality of anticoagulation management remains an important risk factor for dementia in all patients. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

[Chronic outcome of patients with paroxysmal atrial fibrillation post catheter ablation].

PubMed

Lin, Yu-bi; Xia, Yun-long; Gao, Lian-jun; Chu, Zhen-liang; Cong, Pei-xin; Chang, Dong; Yin, Xiao-meng; Zhang, Shu-long; Yang, Dong-Hui; Yang, Yan-Zong

2009-12-01

High short-term successful rate was reported for catheter ablation in patients with paroxysmal atrial fibrillation (AF), we analyzed the long-term outcome (success rate, anticoagulation therapy and embolism event, anti-arrhythmic therapy and death post procedure) of catheter ablation for paroxysmal AF in this study. From January 2000 to December 2004, 106 consecutive patients with drug-refractory paroxysmal AF underwent catheter ablation and were followed-up for (60.7 + or - 11.8) months. Segmental pulmonary vein isolation (SPVI) was routinely performed by radiofrequency energy under the guidance of circular mapping catheter. The patients were followed up with 24 h-holter, ECG, telephone or letter. Data on recurrence of AF, the anticoagulation medication and the incidence of embolism, anti-arrhythmic therapy were obtained. There were 9 patients lost to follow up. In the remaining 97 patients [65 males, (54.8 + or - 11.2) years old], 3 cases died from cancer, sinus rhythm was maintained in 68 patients (Group S, 72.3%) and AF recurrence evidenced in 26 patients (Group R, 27.7%). In Group S, 56 patients (82.4%) discontinued anticoagulation medication, and 12 patients continued to take aspirin. There was no embolism event in Group S during follow-up. In Group R, 1 patient continued to take warfarin; 11 patients continued to take aspirin and 2 patients suffered from cerebral embolism. Anticoagulation medication was discontinued in 14 patients (53.8%) and 1 patient suffered form cerebral embolism. The incidence of embolism event in Group R is significantly higher than in Group S (P < 0.01). More patients discontinued anti-arrhythmic medication in Group S than in Group R (80.9% vs. 56.0%, P < 0.05). Catheter ablation is associated with satisfactory long-term success rate, reduced anti-arrhythmia medication, improved quality of life in patients with paroxysmal AF.

Antithrombotic treatment in elderly patients with atrial fibrillation.

PubMed

Suárez Fernández, C; Camafort, M; Cepeda Rodrigo, J M; Díez-Manglano, J; Formiga, F; Pose Reino, A; Tiberio, G; Mostaza, J M

2015-04-01

Atrial fibrillation (AF) in the elderly is a complex condition due to the high number of frequently associated comorbidities, such as cardiovascular and kidney disease, cognitive disorders, falls and polypharmacy. Except when contraindicated, anticoagulation is necessary for preventing thromboembolic events in this population. Both vitamin K antagonists and direct oral anticoagulants (dabigatran, rivaroxaban and apixaban) are indicated in this context. Renal function should be closely monitored for this age group when these drugs are used. In recent years, various clinical practice guidelines have been published on patients with AF. The majority of these guidelines make specific recommendations on the clinical characteristics and treatment of elderly patients. In this update, we review the specific comments on the recommendations concerning antithrombotic treatment in elderly patients with nonvalvular AF. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Current issues in patient adherence and persistence: focus on anticoagulants for the treatment and prevention of thromboembolism

PubMed Central

Kneeland, Patrick P; Fang, Margaret C

2010-01-01

Warfarin therapy reduces morbidity and mortality related to thromboembolism. Yet adherence to long-term warfarin therapy remains challenging due to the risks of anticoagulant-associated complications and the burden of monitoring. The aim of this paper is to review determinants of adherence and persistence on long-term anticoagulant therapy for atrial fibrillation and venous thromboembolism. We evaluate what the current literature reveals about the impact of warfarin on quality of life, examine warfarin trial data for patterns of adherence, and summarize known risk factors for warfarin discontinuation. Studies suggest only modest adverse effects of warfarin on quality of life, but highlight the variability of individual lifestyle experiences of patients on warfarin. Interestingly, clinical trials comparing anticoagulant adherence to alternatives (such as aspirin) show that discontinuation rates on warfarin are not consistently higher than in control arms. Observational studies link a number of risk factors to warfarin non-adherence including younger age, male sex, lower stroke risk, poor cognitive function, poverty, and higher educational attainment. In addition to differentiating the relative impact of warfarin-associated complications (such as bleeding) versus the lifestyle burdens of warfarin monitoring on adherence, future investigation should focus on optimizing patient education and enhancing models of physician–patient shared-decision making around anticoagulation. PMID:20361065

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

[A prompt diagnosis of Steinert's dystrophy in emergency unit].

PubMed

Suppa, M; Migliozzi, E; Magnanelli, E; Negri, S; Cavicchi, F; Colzi, M; Coppola, A

2012-11-01

Atrial fibrillation is frequently observed in Fist Aid. A rare cause is myotonic dystrophy There are two forms: Steinert's dystrophy caused by a defect of a gene myotoninaprotein kinase and Promm secondary to a defect of a Zinc Finger Protein Gene Clinical manifestations are localized in skeletal and face muscles, vitreous body, sexual glands, endocrine system, smooth muscle, central nervous system and myocardium. Sometimes, in mild and unrecognized forms of this rare disease there are arrhythmias as atrial fibrillation. We report the clinical case of a 52 year-old man, with a suspect diagnosis of Steinert's dystrophy, admitted to the emergency room for a persistent atrial fibrillation. The patient begins oral anticoagulation therapy. The patient perform a transesophageal echocardiogram before the electrical cardioversion with reset to sinus rhythm. In conclusion, with improving the screening methods of patients with primary and secondary myopathies, it has been seen an increase of cases in which a cardiac involvement occurred before or after the onset of the neuromuscular disorders. One of the most frequent alterations is represented by atrial fibrillation, responsible for an increased risk of cerebral embolism, with absolute indication for oral anticoagulation therapy. The myopathy more frequently associated with atrial fibrillation, is myotonic dystrophy, although the risk of cerebral embolism in these patients does not appear to be higher than the general population. The present case report is a spur to perform the diagnosis of Steinert disease in cases admitted to an Emergency Room because of arrhytmias, because of the possibility to perform fast and reliable specific genetic tests. A similar praxis confers to these Units an even more diagnostic clinical role.

Effect of access to anticoagulation management services on warfarin use in patients with atrial fibrillation.

PubMed

Burkiewicz, Jill S

2005-08-01

To determine the effect of access to ambulatory anticoagulation management services (AMS) on the rate of warfarin use in patients with atrial fibrillation. Retrospective medical record review. Two ambulatory care clinics in the same managed care system: one with and one without access to pharmacist-managed AMS. One hundred seventy-eight patients with atrial fibrillation diagnosed between June 2000 and June 2001. Warfarin use was assessed overall and by contraindications and risk factors for stroke. Independent predictors of therapy were identified. The overall rate of warfarin use in atrial fibrillation was higher in the clinic with access to AMS than in the clinic without access (77.9% vs 61.7%, p=0.03). In patients with no known contraindications, warfarin use increased by 20.2% with access to AMS versus no access (80.2% vs 60.0%, p=0.023). Patients aged 65 years or older with one or more risk factors for stroke and no contraindications were more likely to receive warfarin in the clinic with access to AMS than in the clinic without access (85.1% vs 53.8%, p=0.001). Access to AMS was an independent predictor of warfarin use (odds ratio 2.19, 95% confidence interval [CI] 1.05-4.56). Female sex was an independent negative predictor of warfarin use (odds ratio 0.48, 95% CI 0.24-0.96). In the managed care setting, use of warfarin for stroke prophylaxis in patients with atrial fibrillation was higher in the ambulatory care clinic with access to pharmacist-managed AMS than in the clinic without access.

Effects of novel oral anticoagulants on left atrial and left atrial appendage thrombi: an appraisal.

PubMed

Marsico, Fabio; Cecere, Milena; Parente, Antonio; Paolillo, Stefania; de Martino, Fabiana; Dellegrottaglie, Santo; Trimarco, Bruno; Perrone Filardi, Pasquale

2017-02-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and predisposes to an increased risk of thromboembolic events. Patients affected by AF exhibit an increased risk of stroke compared with those in sinus rhythm, with the most common location of thrombi in the left atrial appendage. Until 2009, warfarin and other vitamin K antagonists were the only class of oral anticoagulants available. More recently, dabigatran, rivaroxaban, apixaban, and edoxaban have been approved by regulatory authorities for prevention of stroke in patients with non-valvular AF. Few data are available about the efficacy of novel oral anticoagulants for the treatment of left atrial and left atrial appendage thrombosis. Aim of this review is to summarize available evidence regarding the effectiveness of novel oral anticoagulants on left atrial appendage thrombosis.

Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin.

PubMed

Vinereanu, Dragos; Lopes, Renato D; Mulder, Hillary; Gersh, Bernard J; Hanna, Michael; de Barros E Silva, Pedro G M; Atar, Dan; Wallentin, Lars; Granger, Christopher B; Alexander, John H

2017-12-01

Few data exist on the long-term outcomes of patients with spontaneous echo contrast (SEC), left atrial/left atrial appendage (LA/LAA) thrombus, and complex aortic plaque (CAP), in patients with atrial fibrillation receiving oral anticoagulation. We explored the relationship between these 3 echocardiographic findings and clinical outcomes, and the comparative efficacy and safety of apixaban and warfarin for each finding. Patients from the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) with SEC, LA/LAA thrombus, or CAP diagnosed by either transthoracic or transesophageal echocardiography were compared with patients with none of these findings on transesophageal echocardiography. A total of 1251 patients were included: 217 had SEC, 127 had LA/LAA thrombus, 241 had CAP, and 746 had none. The rates of stroke/systemic embolism were not significantly different among patients with and without these echocardiographic findings (hazard ratio, 0.96; 95% confidence interval, 0.25-3.60 for SEC; hazard ratio, 1.27; 95% confidence interval, 0.23-6.86 for LA/LAA thrombus; hazard ratio, 2.21; 95% confidence interval, 0.71-6.85 for CAP). Rates of ischemic stroke, myocardial infarction, cardiovascular death, and all-cause death were also not different between patients with and without these findings. For patients with either SEC or CAP, there was no evidence of a differential effect of apixaban over warfarin. For patients with LA/LAA thrombus, there was also no significant interaction, with the exception of all-cause death and any bleeding where there was a greater benefit of apixaban compared with warfarin among patients with no LA/LAA thrombus. In anticoagulated patients with atrial fibrillation and risk factors for stroke, echocardiographic findings do not seem to add to the risk of thromboembolic events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2017 American Heart Association, Inc.

Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events--European Registry in Atrial Fibrillation (PREFER in AF).

PubMed

Kirchhof, Paulus; Ammentorp, Bettina; Darius, Harald; De Caterina, Raffaele; Le Heuzey, Jean-Yves; Schilling, Richard John; Schmitt, Josef; Zamorano, Jose Luis

2014-01-01

We sought to describe the management of patients with atrial fibrillation (AF) in Europe after the release of the 2010 AF Guidelines of the European Society of Cardiology. The PREFER in AF registry enrolled consecutive patients with AF from January 2012 to January 2013 in 461 centres in seven European countries. Seven thousand two hundred and forty-three evaluable patients were enrolled, aged 71.5 ± 11 years, 60.1% male, CHA2DS2VASc score 3.4 ± 1.8 (mean ± standard deviation). Thirty per cent patients had paroxysmal, 24.0% had persistent, 7.2% had long-standing persistent, and 38.8% had permanent AF. Oral anticoagulation was used in the majority of patients: 4799 patients (66.3%) received a vitamin K antagonist (VKA) as mono-therapy, 720 patients a combination of VKA and antiplatelet agents (9.9%), 442 patients (6.1%) a new oral anticoagulant drugs (NOAC). Antiplatelet agents alone were given to 808 patients (11.2%), no antithrombotic therapy to 474 patients (6.5%). Of 7034 evaluable patients, 5530 (78.6%) patients were adequately rate controlled (mean heart rate 60-100 bpm). Half of the patients (50.7%) received rhythm control therapy by electrical cardioversion (18.1%), pharmacological cardioversion (19.5%), antiarrhythmic drugs (amiodarone 24.1%, flecainide or propafenone 13.5%, sotalol 5.5%, dronedarone 4.0%), and catheter ablation (5.0%). The management of AF patients in 2012 has adapted to recent evidence and guideline recommendations. Oral anticoagulant therapy with VKA (majority) or NOACs is given to over 80% of eligible patients, including those at risk for bleeding. Rate is often adequately controlled, and rhythm control therapy is widely used.

HRS/NSA 2014 Survey of Atrial Fibrillation and Stroke: Gaps in Knowledge and Perspective, Opportunities for Improvement.

PubMed

Frankel, David S; Parker, Sarah E; Rosenfeld, Lynda E; Gorelick, Philip B

2015-08-01

The prevalence of atrial fibrillation (AF) is substantial and increasing. Stroke is common in AF and can have devastating consequences. Oral anticoagulants are effective in reducing stroke risk, but are underutilized. We sought to characterize the impact of stroke on AF patients and their caregivers, gaps in knowledge and perspective between physicians and patients, and barriers to effective communication and optimal anticoagulation use. A survey was administered to AF patients with and without history of stroke, caregivers of stroke survivors, and physicians across the range of specialties caring for AF and stroke patients. While AF patients (n = 499) had limited knowledge about stroke, they expressed great desire to learn more and take action to reduce their risk. They were often dissatisfied with the education they had received and desired high-quality written materials. Stroke survivors (n = 251) had poor functional outcomes and often underestimated the burden of caring for them. Caregivers (n = 203) also wished they had received more information about reducing stroke risk before their survivor's event. They commonly felt overwhelmed and socially isolated. Physicians (n = 504) did not prescribe anticoagulants as frequently as recommended by guidelines. Concerns about monitoring anticoagulation and patient compliance were commonly reported barriers. Physicians may underestimate patient willingness to take anticoagulants. We identified significant knowledge gaps among patients, caregivers, and physicians in relation to AF and stroke. Furthermore, gaps in perspective often lead to suboptimal communication and decision making. Increased education and better communication between all stakeholders are needed to reduce the impact of stroke in AF. Copyright © 2015 Heart Rhythm Society and National Stroke Association. Published by Elsevier Inc. All rights reserved.

HRS/NSA 2014 survey of atrial fibrillation and stroke: Gaps in knowledge and perspective, opportunities for improvement.

PubMed

Frankel, David S; Parker, Sarah E; Rosenfeld, Lynda E; Gorelick, Philip B

2015-08-01

The prevalence of atrial fibrillation (AF) is substantial and increasing. Stroke is common in AF and can have devastating consequences. Oral anticoagulants are effective in reducing stroke risk, but are underutilized. We sought to characterize the impact of stroke on AF patients and their caregivers, gaps in knowledge and perspective between physicians and patients, and barriers to effective communication and optimal anticoagulation use. A survey was administered to AF patients with and without history of stroke, caregivers of stroke survivors, and physicians across the range of specialties caring for AF and stroke patients. While AF patients (n = 499) had limited knowledge about stroke, they expressed great desire to learn more and take action to reduce their risk. They were often dissatisfied with the education they had received and desired high-quality written materials. Stroke survivors (n = 251) had poor functional outcomes and often underestimated the burden of caring for them. Caregivers (n = 203) also wished they had received more information about reducing stroke risk before their survivor's event. They commonly felt overwhelmed and socially isolated. Physicians (n = 504) did not prescribe anticoagulants as frequently as recommended by guidelines. Concerns about monitoring anticoagulation and patient compliance were commonly reported barriers. Physicians may underestimate patient willingness to take anticoagulants. We identified significant knowledge gaps among patients, caregivers, and physicians in relation to AF and stroke. Furthermore, gaps in perspective often lead to suboptimal communication and decision making. Increased education and better communication between all stakeholders are needed to reduce the impact of stroke in AF. Copyright © 2015 Heart Rhythm Society and National Stroke Association. Published by Elsevier Inc. All rights reserved.

Real-world comparison of major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban, or warfarin. A propensity score matched analysis.

PubMed

Lip, Gregory Y H; Keshishian, Allison; Kamble, Shital; Pan, Xianying; Mardekian, Jack; Horblyuk, Ruslan; Hamilton, Melissa

2016-10-28

In addition to warfarin, there are four non-vitamin K antagonist oral anticoagulants (NOACs) available for stroke prevention in non valvular atrial fibrillation (NVAF). There are limited data on the comparative risks of major bleeding among newly anticoagulated NVAF patients who initiate warfarin, apixaban, dabigatran, or rivaroxaban, when used in 'real world' clinical practice. The study used the Truven MarketScan ® Commercial & Medicare supplemental US claims database. NVAF patients aged ≥18 years newly prescribed an oral anticoagulant 01JAN2013-31DEC2014, with a ≥1-year baseline period, were included (study period: 01JAN2012-31DEC2014). Major bleeding was defined as bleeding requiring hospitalisation. Propensity score matching (PSM) was used to balance age, sex, region, baseline comorbidities, and comedications. Cox proportional hazards models were used to estimate the PSM hazard ratio (HR) of major bleeding. Among 45,361 newly anticoagulated NVAF patients, 15,461 (34.1 %) initiated warfarin, 7,438 (16.4 %) initiated apixaban, 17,801 (39.2 %) initiated rivaroxaban, and 4,661 (10.3 %) initiated dabigatran. Compared to matched warfarin initiators, apixaban (HR: 0.53; 95 % CI: 0.39-0.71) and dabigatran (HR: 0.69; 95 % CI: 0.50-0.96) initiators had a significantly lower risk of major bleeding. Patients initiating rivaroxaban (HR: 0.98; 95 % CI: 0.83-1.17) had a non-significant difference in major bleeding risk compared to matched warfarin patients. When comparisons were made between NOACs, matched rivaroxaban patients had a significantly higher risk of major bleeding (HR: 1.82; 95 % CI: 1.36-2.43) compared to apixaban patients. The differences for apixaban-dabigatran and dabigatran-rivaroxaban matched cohorts were not statistically significant. Among newly anticoagulated NVAF patients in the real-world setting, apixaban and dabigatran initiation was associated with significantly lower risk of major bleeding compared to warfarin initiation. When compared to apixaban, rivaroxaban initiation was associated with significantly higher risk of major bleeding.

Aligning health care policy with evidence-based medicine: the case for funding direct oral anticoagulants in atrial fibrillation.

PubMed

Stone, James A; Earl, Karen M; O'Neill, Blair J; Sharma, Mukul; Huynh, Thao; Leblanc, Kori; Ward, Richard; Teal, Philip A; Cox, Jafna L

2014-10-01

Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Warfarin for stroke prevention in octogenarians with atrial fibrillation.

PubMed

Howard, P A; Ellerbeck, E F; Engelman, K K; Dunn, M I

2001-01-01

The authors examined warfarin use in elderly patients with atrial fibrillation. Medical records were abstracted from a random sample of Medicare beneficiaries with atrial fibrillation who were discharged from Kansas hospitals. Data were analyzed for warfarin and aspirin use and risk factors for stroke or bleeding in patients 65-79 years of age or 80 years and older. Stroke risk factors other than age and atrial fibrillation were seen in 98% of 142 patients less than 80 years of age and 100% of 141 octogenarians. Warfarin use was similar in the younger and older age groups (50% vs. 45%, respectively; p = ns) and was not associated with the number of stroke or bleeding risk factors. Compared to patients less than 80 years of age, octogenarians were less likely to receive aspirin (38% vs. 27%, respectively; p < 0.05). Anticoagulation rates for high-risk patients with atrial fibrillation were low and poorly explained by stroke or bleeding risks.

Atrial fibrillation

PubMed Central

Munger, Thomas M.; Wu, Li-Qun; Shen, Win K.

2014-01-01

Atrial fibrillation is the most common arrhythmia affecting patients today. Disease prevalence is increasing at an alarming rate worldwide, and is associated with often catastrophic and costly consequences, including heart failure, syncope, dementia, and stroke. Therapies including anticoagulants, anti-arrhythmic medications, devices, and non-pharmacologic procedures in the last 30 years have improved patients' functionality with the disease. Nonetheless, it remains imperative that further research into AF epidemiology, genetics, detection, and treatments continues to push forward rapidly as the worldwide population ages dramatically over the next 20 years. PMID:24474959

The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study.

PubMed

Hijazi, Ziad; Oldgren, Jonas; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Held, Claes; Hylek, Elaine M; Lopes, Renato D; Siegbahn, Agneta; Yusuf, Salim; Granger, Christopher B; Wallentin, Lars

2016-06-04

The benefit of oral anticoagulation in atrial fibrillation is based on a balance between reduction in ischaemic stroke and increase in major bleeding. We aimed to develop and validate a new biomarker-based risk score to improve the prognostication of major bleeding in patients with atrial fibrillation. We developed and internally validated a new biomarker-based risk score for major bleeding in 14,537 patients with atrial fibrillation randomised to apixaban versus warfarin in the ARISTOTLE trial and externally validated it in 8468 patients with atrial fibrillation randomised to dabigatran versus warfarin in the RE-LY trial. Plasma samples for determination of candidate biomarker concentrations were obtained at randomisation. Major bleeding events were centrally adjudicated. The predictive values of biomarkers and clinical variables were assessed with Cox regression models. The most important variables were included in the score with weights proportional to the model coefficients. The ARISTOTLE and RE-LY trials are registered with ClinicalTrials.gov, numbers NCT00412984 and NCT00262600, respectively. The most important predictors for major bleeding were the concentrations of the biomarkers growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (cTnT-hs) and haemoglobin, age, and previous bleeding. The ABC-bleeding score (age, biomarkers [GDF-15, cTnT-hs, and haemoglobin], and clinical history [previous bleeding]) score yielded a higher c-index than the conventional HAS-BLED and the newer ORBIT scores for major bleeding in both the derivation cohort (0·68 [95% CI 0·66-0·70] vs 0·61 [0·59-0·63] vs 0·65 [0·62-0·67], respectively; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0008). ABC-bleeding score also yielded a higher c-index score in the the external validation cohort (0·71 [95% CI 0·68-0·73] vs 0·62 [0·59-0·64] for HAS-BLED vs 0·68 [0·65-0·70] for ORBIT; ABC-bleeding vs HAS-BLED p<0·0001 and ABC-bleeding vs ORBIT p=0·0016). A modified ABC-bleeding score using alternative biomarkers (haematocrit, cTnI-hs, cystatin C, or creatinine clearance) also outperformed the HAS-BLED and ORBIT scores. The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) was internally and externally validated and calibrated in large cohorts of patients with atrial fibrillation receiving anticoagulation therapy. The ABC-bleeding score performed better than HAS-BLED and ORBIT scores and should be useful as decision support on anticoagulation treatment in patients with atrial fibrillation. BMS, Pfizer, Boehringer Ingelheim, Roche Diagnostics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry.

PubMed

Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph Gabriel

2015-01-01

Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. ISRCTN registry of clinical trials: ISRCTN43070564.

Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry

PubMed Central

Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M.; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph. Gabriel

2015-01-01

Background Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. Methods and Findings CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. Conclusions In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. Trial Registration ISRCTN registry of clinical trials: ISRCTN43070564. PMID:25915904

To Bleed or Not to Bleed: That is the Question. The Side Effects of Apixaban.

PubMed

Ciccone, Marco Matteo; Zito, Annapaola; Devito, Fiorella; Maiello, Maria; Palmiero, Pasquale

2018-01-01

Apixaban is a new oral anticoagulant (NOACs: Novel Oral Anticoagulant), like dabigatran, rivaroxaban, and edoxaban. All of them are prescribed to patients with non valvular atrial fibrillation or venous thromboembolism, to replace warfarin, because of the lower probability of bleeding, however they can cause bleeding by themselves. Bleeding is an adverse event in patients taking anticoagulants. It is associated with a significant increase of morbidity and risk of death. However, these drugs should be used only for the time when anticoagulation is strictly required, especially when used for preventing deep vein thrombosis. Prolonged use increases the risk of bleeding. In the ARISTOTLE Trial Apixaban, compared with warfarin, was associated with a lower rate of intracranial hemorrhages and less adverse consequences following extracranial hemorrhage. Many physicians still have limited experience with new oral anticoagulants and about bleeding risk managment. We reviewed the available literature on extracranial and intracranial bleeding concerning apixaban. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Exploration of adherence and patient experiences with DOACs one year after switching from vitamin-K antagonists- insights from the switching study.

PubMed

Bartoli-Abdou, John K; Patel, Jignesh P; Crawshaw, Jacob; Vadher, Bipin; Brown, Alison; Roberts, Lara N; Patel, Raj K; Arya, Roopen; Auyeung, Vivian

2018-02-01

Current UK and European guidelines recommend anticoagulated patients prescribed warfarin with time in therapeutic range (TTR) <65% be considered for DOAC therapy. There has been considerable concern that adherence with DOACs may be poor compared with warfarin. Little is known about the patient experience of switching from warfarin to DOAC and how patients manage their DOAC long term. Our aim was to conduct focus groups exploring patient's previous experiences with warfarin, their current experience with DOACs, their adherence to DOACs and the long-term service provision they envisage. Patients enrolled on the Switching Study who had been switched from warfarin to a DOAC >1year previously were invited to participate in focus groups. Two focus groups for atrial fibrillation (AF) and two for secondary prevention of venous thromboembolism (VTE) patients were held at anticoagulation clinics in South London, UK. Data was analysed using framework analysis to extract dominant themes. Five VTE patients and 15 AF patients attended the focus groups. Dominant themes that emerged were: indication specific anticoagulation prioritisation, warfarin as a necessary inconvenience, DOACs as the anticoagulant of choice, concerns regarding DOAC monitoring, high adherence to DOACs and desire for long-term access to specialist anticoagulation services. VTE patients prioritised anticoagulation over other therapies whereas AF patients did not. All participants reported high levels of adherence to DOACs. Patients derived confidence from long-term management in specialist anticoagulation clinics stating a preference to be managed in such a service. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Summary of evidence-based guideline update: Prevention of stroke in nonvalvular atrial fibrillation

PubMed Central

Culebras, Antonio; Messé, Steven R.; Chaturvedi, Seemant; Kase, Carlos S.; Gronseth, Gary

2014-01-01

Objective: To update the 1998 American Academy of Neurology practice parameter on stroke prevention in nonvalvular atrial fibrillation (NVAF). How often do various technologies identify previously undetected NVAF? Which therapies reduce ischemic stroke risk with the least risk of hemorrhage, including intracranial hemorrhage? The complete guideline on which this summary is based is available as an online data supplement to this article. Methods: Systematic literature review; modified Delphi process recommendation formulation. Major conclusions: In patients with recent cryptogenic stroke, cardiac rhythm monitoring probably detects occult NVAF. In patients with NVAF, dabigatran, rivaroxaban, and apixaban are probably at least as effective as warfarin in preventing stroke and have a lower risk of intracranial hemorrhage. Triflusal plus acenocoumarol is likely more effective than acenocoumarol alone in reducing stroke risk. Clopidogrel plus aspirin is probably less effective than warfarin in preventing stroke and has a lower risk of intracranial bleeding. Clopidogrel plus aspirin as compared with aspirin alone probably reduces stroke risk but increases the risk of major hemorrhage. Apixaban is likely more effective than aspirin for decreasing stroke risk and has a bleeding risk similar to that of aspirin. Major recommendations: Clinicians might obtain outpatient cardiac rhythm studies in patients with cryptogenic stroke to identify patients with occult NVAF (Level C) and should routinely offer anticoagulation to patients with NVAF and a history of TIA/stroke (Level B). Specific patient considerations will inform anticoagulant selection in patients with NVAF judged to need anticoagulation. PMID:24566225

Prognostic value of trans-thoracic echocardiography in patients with acute stroke and atrial fibrillation: findings from the RAF study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Lees, Kennedy R

2016-02-01

Anticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). T he identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90 days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7 days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3 ± 9.5 years) underwent a TTE evaluation; 63 patients (7.4%) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3%) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2%) among whom 51 (9.3%) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7%. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95% CI 1.06-4.29, p = 0.033) and CHA2DS2-VASc score (OR 1.22; 95% CI 1.04-1.45, p = 0.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon.

Utilization of Anticoagulation Therapy in Medicare Patients with Nonvalvular Atrial Fibrillation

PubMed Central

Fitch, Kate; Broulette, Jonah; Pyenson, Bruce; Iwasaki, Kosuke; Kwong, Winghan Jacqueline

2012-01-01

Background Clinical guidelines recommend oral anticoagulation for stroke prevention in patients with atrial fibrillation (AF) at moderate or high risk for stroke but not at high risk for bleeding; however, studies consistently report suboptimal use of such therapy. This study used Medicare Part D claims data to assess the use of warfarin in the Medicare population. Objectives To compare real-world warfarin utilization with current treatment guideline recommendations, and to assess the effect of warfarin exposure level on patient outcomes in Medicare beneficiaries with nonvalvular AF (NVAF). Methods Patients who were recently diagnosed with NVAF were identified using a random 5% sample of Research Identifiable Files of Medicare beneficiaries in 2006 or 2007. Individuals with moderate-to-high stroke risk per CHADS2 but not at high bleeding risk per ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score were evaluated for warfarin use, as identified by the presence of ≥1 warfarin prescription claims within 12 months after the index diagnosis. Warfarin exposure level was assessed by the proportion of days covered during the 12-month follow-up period. The effect of warfarin exposure on ischemic stroke and major bleeding event rates during the 12-month follow-up period were assessed using multivariate logistic regression. Results Data from 14,149 newly diagnosed patients with NVAF (mean age, 79 years; 58.7% female) were analyzed, and of these, 7524 (53.2%) patients were identified as having moderate-to-high stroke risk and not being at high bleeding risk. Of these patients, 3110 (41.3%) did not receive warfarin within 12 months of the index diagnosis. The risk for ischemic stroke was significantly lower in those with warfarin exposure versus no warfarin exposure (adjusted odds ratio [OR], 0.51; confidence interval [CI], 0.43–0.61; P <.001) and in patients with warfarin proportion of days covered ≥80% versus those with proportion of days covered <80% (adjusted OR, 0.59; 95% CI, 0.48–0.72; P<.001). Warfarin exposure was associated with a significantly higher major bleeding rate (adjusted OR, 1.19; 95% CI, 1.04–1.36; P = .013), with this significant difference being driven by patients aged >65 years. Conclusions Based on a risk-stratification scheme composed of previously published tools, such as CHADS2 and the ATRIA bleeding risk index, a significant proportion of Medicare beneficiaries with AF are not receiving guideline-recommended anticoagulation therapy, which leads to an excess rate of ischemic stroke in this patient population. These findings highlight quality-of-care issues for patients with AF and the need to improve compliance with anticoagulation guidelines in the Medicare population. PMID:24991318

Quality of Vitamin K Antagonist Anticoagulation in Spain: Prevalence of Poor Control and Associated Factors.

PubMed

Anguita Sánchez, Manuel; Bertomeu Martínez, Vicente; Cequier Fillat, Ángel

2015-09-01

To study the prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain in patients with nonvalvular atrial fibrillation, and to identify associated factors. We studied 1056 consecutive patients seen at 120 cardiology clinics in Spain between November 2013 and March 2014. We analyzed the international normalized ratio from the 6 months prior to the patient's visit, calculating the prevalence of poorly controlled anticoagulation, defined as < 65% time in therapeutic range using the Rosendaal method. Mean age was 73.6 years (standard deviation, 9.8 years); women accounted for 42% of patients. The prevalence of poorly controlled anticoagulation was 47.3%. Mean time in therapeutic range was 63.8% (25.9%). The following factors were independently associated with poorly controlled anticoagulation: kidney disease (odds ratio = 1.53; 95% confidence interval, 1.08-2.18; P = .018), routine nonsteroidal anti-inflammatory drugs (odds ratio = 1.79; 95% confidence interval, 1.20-2.79; P = .004), antiplatelet therapy (odds ratio = 2.16; 95% confidence interval, 1.49-3.12; P < .0001) and absence of angiotensin receptor blockers (odds ratio = 1.39; 95% confidence interval, 1.08-1.79; P = .011). There is a high prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain. Factors associated with poor control are kidney disease, routine nonsteroidal anti-inflammatory drugs, antiplatelet use, and absence of angiotensin receptor blockers. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Potential use of NOACs in developing countries: pros and cons.

PubMed

Bista, Durga; Chalmers, Leanne; Bereznicki, Luke; Peterson, Gregory

2014-07-01

Although vitamin K antagonists (VKAs) are effective for long-term thromboprophylaxis in atrial fibrillation (AF), their limitations have led to widespread underutilisation, especially in the developing world. Novel oral anticoagulants (NOACs) have emerged as promising alternatives to VKAs, although there are some particular considerations and challenges to their introduction in developing countries. This review summarises the current state of antithrombotic management of AF in the developing world, explores the early evidence for the NOACs and describes some of the special considerations that must be taken into account when considering the role of the NOACs within developing countries' health care systems. A literature search was conducted via PubMed and Google Scholar to find articles published in English between the years 2000 to 2014. Search terms used were "atrial fibrillation", "oral anticoagulants", "warfarin", "NOACs", "dabigatran", "rivaroxaban", "apixaban", "edoxaban", "time in therapeutic range", "International Normalized Ratio" "cost-effectiveness", "stroke", "adverse-drug reactions" and "drug-drug interactions", together with the individual names of developing countries as listed by the World Bank. We reviewed the results of randomized clinical trials, relevant retrospective and prospective studies, case-studies and review articles. Many developing countries lack or have sporadic data on the quality of AF management, making it difficult to anticipate the potential impact of NOACs in these settings. The utilisation of anticoagulants for AF appears highly variable in developing countries. Given the issues associated with VKA therapy in many developing countries, NOACs offer some potential advantages; however, there is insufficient evidence to advocate the widespread replacement of warfarin at present. VKAs may continue to have a role in selected patients or countries, especially if alternative monitoring strategies can be utilised. The evaluation of the introduction of NOACs should consider safety, budget concerns and the quality of oral anticoagulation care achieved by each country. Prospective registries will be important in developing countries to better elucidate the comparative safety, efficacy and cost-effectiveness of NOACs and VKAs as NOACs are introduced into practice.

Rivaroxaban vs. warfarin for stroke prevention in patients with nonvalvular atrial fibrillation.

PubMed

Darby-Stewart, Andrea; Dachs, Robert; Graber, Mark A

2012-03-15

Patients with nonvalvular atrial fibrillation and a CHADS2 score of 2 points or more should be placed on warfarin anticoagulation. If they do not meet the CHADS2 criteria for warfarin, then they should receive therapy with aspirin. If a patient's condition is well-controlled on warfarin, this study does not support transitioning him or her to rivaroxaban, the more expensive alternative. Home monitoring of INR should be considered for patients who are capable and motivated to perform self-monitoring. Rivaroxaban has no reversal agent and has significant drug interactions (P-glycoprotein inducers and CYP3A4 inhibitors increase the risk of bleeding; P-glycoprotein inducers reduce effectiveness).

Variations in Anticoagulation Practices Following the Maze Procedure.

PubMed

Chung, Jennifer; Sami, Magdi; Albert, Carole; Varennes, Benoit De

2015-01-01

The current real-world anticoagulation practices following left atrial appendectomy in the context of the Maze procedure are unknown. This is a cohort study of all patients who underwent the Maze procedure with amputation of the left atrial appendage from June 2005 to November 2012. Data was prospectively collected at regular intervals with an interview and Holter monitoring. All patients received anticoagulation for 3 months. Those then kept on anticoagulation and those for whom anticoagulation was stopped were compared in terms of death, bleeding and incidence of stroke. In total, there were 113 patients, of whom 66 were treated with anticoagulation (Group A) and 47 were not (Group B). There were no significant baseline differences between the two groups, including the presence of atrial fibrillation (A:19.7%, B:10.6%, p=0.30), CHADS2 score (A:1.41±1.05, B:1.15±1.08, p=0.19), and left atrial size (A:48.3±7.1mm, B:47.6±7.8 mm, p=0.57). There were 275 patient-years of follow-up, with an average of 2.43 years per patient. Only two patients experienced strokes, both in Group A (p=0.27). Of the 5 bleeding events, 4 occurred in the first 3 months while on anticoagulation and the remaining event occurred in Group A at 3 years post-operatively (p=0.10). No standardized approach to anticoagulation after the Maze procedure is apparent in real-world practice in an urban Canadian setting. Patients who undergo the Maze procedure with amputation of the left atrial appendage are at a low risk of stroke, but the optimal anticoagulation strategy requires further investigation.

Atrial fibrillation detected by continuous electrocardiographic monitoring using implantable loop recorder to prevent stroke in individuals at risk (the LOOP study): Rationale and design of a large randomized controlled trial.

PubMed

Diederichsen, Søren Zöga; Haugan, Ketil Jørgen; Køber, Lars; Højberg, Søren; Brandes, Axel; Kronborg, Christian; Graff, Claus; Holst, Anders Gaarsdal; Nielsen, Jonas Bille; Krieger, Derk; Svendsen, Jesper Hastrup

2017-05-01

Atrial fibrillation (AF) increases the rate of stroke 5-fold, and AF-related strokes have a poorer prognosis compared with non-AF-related strokes. Atrial fibrillation and stroke constitute an intensifying challenge, and health care organizations are calling for awareness on the topic. Previous studies have demonstrated that AF is often asymptomatic and consequently undiagnosed. The implantable loop recorder (ILR) allows for continuous, long-term electrocardiographic monitoring with daily transmission of arrhythmia information, potentially leading to improvement in AF detection and stroke prevention. The LOOP study is an investigator-initiated, randomized controlled trial with 6,000 participants randomized 3:1 to a control group or to receive an ILR with continuous electrocardiographic monitoring. Participants are identified from Danish registries and are eligible for inclusion if 70years or older and previously diagnosed as having at least one of the following conditions: hypertension, diabetes mellitus, heart failure, or previous stroke. Exclusion criteria include history of AF and current oral anticoagulation treatment. When an AF episode lasting ≥6minutes is detected, oral anticoagulation will be initiated according to guidelines. Expected follow-up is 4years. The primary end point is time to stroke or systemic embolism, whereas secondary end points include time to AF diagnosis and death. The LOOP study will evaluate health benefits and cost-effectiveness of ILR as a screening tool for AF to prevent stroke in patients at risk. Secondary objectives include identification of risk factors for the development of AF and characterization of arrhythmias in the population. The trial holds the potential to influence the future of stroke prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

[Quality of care and safety indicators in anticoagulated patients with non-valvular auricular fibrillation and deep venous thromboembolic disease].

PubMed

Ignacio, E; Mira, J J; Campos, F J; López de Sá, E; Lorenzo, A; Caballero, F

To identify and prioritise indicators to assess the quality of care and safety of patients with non-valvular auricular fibrillation (NVAF) and deep vein thrombosis (DVT) treated with anticoagulants. Using the consensus conference technique, a group of professionals and clinical experts, the determining factors of the NVAF and DVT care process were identified, in order to define the quality and safety criteria. A proposal was made for indicators of quality and safety that were prioritised, taking into account a series of pre-established attributes. The selected indicators were classified into indicators of context, safety, action, and outcomes of the intervention in the patient. A set of 114 health care and safety quality indicators were identified, of which 35 were prioritised: 15 for NVAF and 20 for DVT. About half (49%) of the indicators (40% for NVAF and 55% for DVT) applied to patient safety, and 26% (33% for NVAF and 20% for DVT) to the outcomes of interventions in the patient. The present work presents a set of agreed indicators by a group of expert professionals that can contribute to the improvement of the quality of care of patients with NVAF and DVT treated with anticoagulants. Copyright © 2018 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

The safety and adequacy of antithrombotic therapy for atrial fibrillation: a regional cohort study

PubMed Central

Burton, Chris; Isles, Chris; Norrie, John; Hanson, Ruth; Grubb, Elaine

2006-01-01

Background Atrial fibrillation is a common problem in older people. The evidence base for the safety of warfarin and aspirin in atrial fibrillation is largely derived from selective research studies and secondary care. Further assessment of the safety of warfarin in older people with atrial fibrillation in routine primary care is needed. Aim To measure the complication rates and adequacy of warfarin control in a cohort of patients with atrial fibrillation managed in primary care and compare them with published data from controlled trials and community patients with atrial fibrillation not receiving warfarin. Design of study Retrospective review of regional cohort. Setting Twenty-seven general practices in southwest Scotland. Method Case note review of 601 patients previously identified as having atrial fibrillation by GPs. Results The average age of our cohort was 77 years at recruitment. Two hundred and sixty-four (44%) patients died within 5 years of follow up. Three hundred and nine of the 601 (51%) patients with atrial fibrillation took warfarin at some stage during this study. INR (international normalised ratio) was maintained between 2 and 3 for 68% of the time. Bleeding risk was higher in patients taking warfarin than in those on aspirin or no antithrombotic therapy (warfarin 9.0% per year versus aspirin 4.7% per year versus no therapy 4.6% per year). The annual risk of any bleeding complication on warfarin (9%) was similar to that recorded in randomised trials (9.2%) whereas the annual risk of severe bleeding was approximately double (2.6 versus 1.3%). Conclusion Adequacy of anticoagulant control was broadly comparable to that reported in clinical trials, whereas the risk of severe bleeding was higher, possibly reflecting the older age and the comorbidities of our unselected cohort. PMID:16954003

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.

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.

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

Model-based dose selection for phase III rivaroxaban study in Japanese patients with non-valvular atrial fibrillation.

PubMed

Tanigawa, Takahiko; Kaneko, Masato; Hashizume, Kensei; Kajikawa, Mariko; Ueda, Hitoshi; Tajiri, Masahiro; Paolini, John F; Mueck, Wolfgang

2013-01-01

The global ROCKET AF phase III trial evaluated rivaroxaban 20 mg once daily (o.d.) for stroke prevention in atrial fibrillation (AF). Based on rivaroxaban pharmacokinetics in Japanese subjects and lower anticoagulation preferences in Japan, particularly in elderly patients, the optimal dose regimen for Japanese AF patients was considered. The aim of this analysis was dose selection for Japanese patients from a pharmacokinetic aspect by comparison of simulated exposure in Japanese patients with those in Caucasian patients. As a result of population pharmacokinetics-pharmacodynamics analyses, a one-compartment pharmacokinetic model with first-order absorption and direct link pharmacokinetic-pharmacodynamic models optimally described the plasma concentration and pharmacodynamic models (Factor Xa activity, prothrombin time, activated partial thromboplastin time, and HepTest), which were also consistent with previous works. Steady-state simulations indicated 15 mg rivaroxaban o.d. doses in Japanese patients with AF would yield exposures comparable to the 20 mg o.d. dose in Caucasian patients with AF. In conclusion, in the context of the lower anticoagulation targets in Japanese practice, the population pharmacokinetic and pharmacodynamic modeling supports 15 mg o.d. as the principal rivaroxaban dose in J-ROCKET AF.

Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial.

PubMed

Goette, Andreas; Merino, Jose L; Ezekowitz, Michael D; Zamoryakhin, Dmitry; Melino, Michael; Jin, James; Mercuri, Michele F; Grosso, Michael A; Fernandez, Victor; Al-Saady, Naab; Pelekh, Natalya; Merkely, Bela; Zenin, Sergey; Kushnir, Mykola; Spinar, Jindrich; Batushkin, Valeriy; de Groot, Joris R; Lip, Gregory Y H

2016-10-22

Edoxaban, an oral factor Xa inhibitor, is non-inferior for prevention of stroke and systemic embolism in patients with atrial fibrillation and is associated with less bleeding than well controlled warfarin therapy. Few safety data about edoxaban in patients undergoing electrical cardioversion are available. We did a multicentre, prospective, randomised, open-label, blinded-endpoint evaluation trial in 19 countries with 239 sites comparing edoxaban 60 mg per day with enoxaparin-warfarin in patients undergoing electrical cardioversion of non-valvular atrial fibrillation. The dose of edoxaban was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, low bodyweight [≤60 kg], or concomitant use of P-glycoprotein inhibitors) were present. Block randomisation (block size four)-stratified by cardioversion approach (transoesophageal echocardiography [TEE] or not), anticoagulant experience, selected edoxaban dose, and region-was done through a voice-web system. The primary efficacy endpoint was a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular mortality, analysed by intention to treat. The primary safety endpoint was major and clinically relevant non-major (CRNM) bleeding in patients who received at least one dose of study drug. Follow-up was 28 days on study drug after cardioversion plus 30 days to assess safety. This trial is registered with ClinicalTrials.gov, number NCT02072434. Between March 25, 2014, and Oct 28, 2015, 2199 patients were enrolled and randomly assigned to receive edoxaban (n=1095) or enoxaparin-warfarin (n=1104). The mean age was 64 years (SD 10·54) and mean CHA 2 DS 2 -VASc score was 2·6 (SD 1·4). Mean time in therapeutic range on warfarin was 70·8% (SD 27·4). The primary efficacy endpoint occurred in five (<1%) patients in the edoxaban group versus 11 (1%) in the enoxaparin-warfarin group (odds ratio [OR] 0·46, 95% CI 0·12-1·43). The primary safety endpoint occurred in 16 (1%) of 1067 patients given edoxaban versus 11 (1%) of 1082 patients given enoxaparin-warfarin (OR 1·48, 95% CI 0·64-3·55). The results were independent of the TEE-guided strategy and anticoagulation status. ENSURE-AF is the largest prospective randomised clinical trial of anticoagulation for cardioversion of patients with non-valvular atrial fibrillation. Rates of major and CRNM bleeding and thromboembolism were low in the two treatment groups. Daiichi Sankyo provided financial support for the study. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Multidisciplinary meeting about the use of direct oral anticoagulants in nonvalvular atrial fibrillation].

PubMed

Rodríguez-Reyes, Humberto; Arauz-Góngora, Antonio; Asensio-Lafuente, Enrique; Celaya-Cota, Manuel de Jesús; Cordero-Cabra, Alejandro; Guevara-Valdivia, Milton; Izaguirre-Avila, Raúl; Lara-Vaca, Susano; Mariona-Moreno, Vitelio; Martínez-Flores, Enrique; Nava-Townsend, Santiago; Pozas-Garza, Gerardo; Rodríguez-Diez, Gerardo

Knowing the real impact of atrial fibrillation in the stroke, the Sociedad Mexicana of Electrofisiología y Estimulación Cardiaca (SOMEEC) had the initiative to develop a multidisciplinary meeting of experts the with the purpose to update the available scientific evidence from clinical practice guidelines, meta-analyses, controlled clinical trials, and complementing with the experience and views of a group of experts. To meet this goal, SOMEEC gathered a group of specialists in the area of cardiology, electrophysiology, neurology and hematology that given their experience in certain areas, they share the scientific evidence with the panel of experts to leave open a discussion about the information presented in this article. This document brings together the best scientific evidence available and aims to be a useful tool in the decision to use of new oral anticoagulants in nonvalvular atrial fibrillation and ischemic heart disease, or relating to the management of patients with stroke or renal failure, and even those that will be submitted to elective surgery and invasive procedures. In the same, they handled comparative schemes of follow-up and treatment which simplifies the decision making by the specialists participants. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Cerebral Amyloid Angiopathy: Diagnosis, Clinical Implications, and Management Strategies in Atrial Fibrillation.

PubMed

DeSimone, Christopher V; Graff-Radford, Jonathan; El-Harasis, Majd A; Rabinstein, Alejandro A; Asirvatham, Samuel J; Holmes, David R

2017-08-29

With an aging population, clinicians are more frequently encountering patients with atrial fibrillation who are also at risk of intracerebral hemorrhage due to cerebral amyloid angiopathy, the result of β-amyloid deposition in cerebral vessels. Cerebral amyloid angiopathy is common among elderly patients, and is associated with an increased risk of intracerebral bleeding, especially with the use of anticoagulation. Despite this association, this entity is absent in current risk-benefit analysis models, which may result in underestimation of the chance of bleeding in the subset of patients with this disease. Determining the presence and burden of cerebral amyloid angiopathy is particularly important when planning to start or restart anticoagulation after an intracerebral hemorrhage. Given the lack of randomized trial data to guide management strategies, we discuss a heart-brain team approach that includes clinician-patient shared decision making for the use of pharmacologic and nonpharmacologic approaches to diminish stroke risk. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Diagnosis and Treatment of Atrial Fibrillation.

PubMed

Gutierrez, Cecilia; Blanchard, Daniel G

2016-09-15

Atrial fibrillation is a supraventricular arrhythmia that adversely affects cardiac function and increases the risk of stroke. It is the most common arrhythmia and a major source of morbidity and mortality; its prevalence increases with age. Pulse rate is sensitive, but not specific, for diagnosis, and suspected atrial fibrillation should be confirmed with 12-lead electrocardiography. Because normal electrocardiographic findings do not rule out atrial fibrillation, home monitoring is recommended if there is clinical suspicion of arrhythmia despite normal test results. Treatment is based on decisions made regarding when to convert to normal sinus rhythm vs. when to treat with rate control, and, in either case, how to best reduce the risk of stroke. For most patients, rate control is preferred to rhythm control. Ablation therapy is used to destroy abnormal foci responsible for atrial fibrillation. Anticoagulation reduces the risk of stroke while increasing the risk of bleeding. The CHA2DS2-VASc scoring system assesses the risk of stroke, with a score of 2 or greater indicating a need for anticoagulation. The HAS-BLED score estimates the risk of bleeding. Scores of 3 or greater indicate high risk. Warfarin, dabigatran, factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban), and aspirin are options for stroke prevention. Selection of therapy should be individualized based on risks and potential benefits, cost, and patient preference. Left atrial appendage obliteration is an option for reducing stroke risk. Two implantable devices used to occlude the appendage, the Watchman and the Amplatzer Cardiac Plug, appear to be as effective as warfarin in preventing stroke, but they are invasive. Another percutaneous approach to occlusion, wherein the left atrium is closed off using the Lariat, is also available, but data on its long-term effectiveness and safety are still limited. Surgical treatments for atrial fibrillation are reserved for patients who are undergoing cardiac surgery for other reasons.

Effect of pre-procedural interrupted apixaban on heparin anticoagulation during catheter ablation for atrial fibrillation: a prospective observational study.

PubMed

Bin Abdulhak, Aref A; Kennedy, Kevin F; Gupta, Sanjaya; Giocondo, Michael; Ramza, Brian; Wimmer, Alan P

2015-11-01

Effective intraprocedural anticoagulation is considered essential to minimize the risk of thromboembolism in catheter ablation (CA) of atrial fibrillation (AF). The effect of interrupted apixaban on intraprocedural heparin dosing requirements and levels of achieved anticoagulation with heparin has not been well studied. The purpose of the present study was to compare heparin administration and activated clotted times (ACTs) for patients undergoing CA for AF treated with interrupted apixaban before the procedure with patients on uninterrupted warfarin. Consecutive patients undergoing CA for AF treated with interrupted apixaban or uninterrupted warfarin were prospectively enrolled. Heparin administration determined by a standard protocol and normalized to patient weight and procedure duration, as well as rapidity, and degree of anticoagulation with heparin (as measured by mean ACT, peak ACT, time to ACT ≥300 s, and time to ACT ≥350 s) were compared between the groups. Forty-eight patients were enrolled (25 apixaban and 23 warfarin). Heparin administered by bolus (51.3 ± 21.5 vs 27.8 ± 9.6 units/kg/h; p < 0.001) and mean heparin drip rate (25.3 ± 3.6 vs 20.7 ± 2.4 units/kg/h; p < 0.001) were significantly higher in the apixaban group compared to the warfarin group. Despite greater heparin administration, apixaban patients achieved a significantly lower mean ACT (332.3 ± 17.0 vs 384.5 ± 53.9; p < 0.001) and peak ACT (369.5 ± 22.6 vs 432.3 ± 75.8, p < 0.001) compared to the warfarin group. The time to ACT ≥350 s (66.7 ± 35.8 vs 26.9 ± 34.0; p < 0.001) was significantly longer for apixaban-treated patients. Outcome differences persisted after analysis using linear models and Cox proportional hazard regression with adjustment for propensity scores. A standard intraprocedural heparin protocol results in delayed and lower levels of anticoagulation as measured by the ACT for interrupted apixaban-treated patients in comparison to those on uninterrupted warfarin during CA of AF.

Anticoagulation Bridge Therapy in Patients with Atrial Fibrillation: Recent Updates Providing a Rebalance of Risk and Benefit.

PubMed

Garwood, Candice L; Korkis, Bianca; Grande, Domenico; Hanni, Claudia; Morin, Amy; Moser, Lynette R

2017-06-01

In 2011 we reviewed clinical updates and controversies surrounding anticoagulation bridge therapy in patients with atrial fibrillation (AF). Since then, options for oral anticoagulation have expanded with the addition of four direct oral anticoagulant (DOAC) agents available in the United States. Nonetheless, vitamin K antagonist (VKA) therapy continues to be the treatment of choice for patients who are poor candidates for a DOAC and for whom bridge therapy remains a therapeutic dilemma. This literature review identifies evidence and guideline and consensus statements from the last 5 years to provide updated recommendations and insight into bridge therapy for patients using a VKA for AF. Since our last review, at least four major international guidelines have been updated plus a new consensus document addressing bridge therapy was released. Prospective trials and one randomized controlled trial have provided guidance for perioperative bridge therapy. The clinical trial data showed that bridging with heparin is associated with a significant bleeding risk compared with not bridging; furthermore, data suggested that actual perioperative thromboembolic risk may be lower than previously estimated. Notably, patients at high risk for stroke have not been adequately represented. These findings highlight the importance of assessing thrombosis and bleeding risk before making bridging decisions. Thrombosis and bleeding risk tools have emerged to facilitate this assessment and have been incorporated into guideline recommendations. Results from ongoing trials are expected to provide more guidance on safe and effective perioperative management approaches for patients at high risk for stroke. © 2017 Pharmacotherapy Publications, Inc.

Pacemaker diagnostics in atrial fibrillation: limited usefulness for therapy initiation in a pacemaker practice.

PubMed

Yedlapati, Neeraja; Fisher, John D

2014-09-01

We aimed to determine the practical value of pacemaker diagnostics for atrial fibrillation (AF) in an unselected general pacemaker practice, specifically workflow and initiation of anticoagulation or antiarrhythmic drug (AAD) therapy. We prospectively followed consecutive pacemaker interrogations over a period of 1 year to identify patients with AF (burden from 1% to 99%). We contacted referring physicians with AF details, and then determined whether the information resulted in therapeutic changes. Of the 1,100 pacemakers interrogated, 728 were dual chamber (DDDs) with AF diagnostic capability. AF was recorded in 73 (10%) but seven had limited information, leaving 66 patients; of these, 42 (63%) patients were already anticoagulated and in five (7%) patients, anticoagulation had been stopped because of complications. Initial diagnosis of AF was made by the pacemaker in 17 patients (26% of 66; 2% of 728); four (6% of 66) patients were newly initiated on anticoagulation. Of the 66 patients, 17 patients were already on AADs; 49 (74%) had satisfactory rate control or had other issues; only two (3% of 66; 0.3% of 728) received new AADs. Of 728 patients with DDD pacemakers, only 17 were newly discovered to have AF, and six (0.8%) had changes in medications based on the pacemaker data. Adding pacemaker-derived data to existing clinical information had little therapeutic impact, due to a combination of cumbersome workflow, and because AF was usually known to practitioners. Developments in automated monitoring systems may provide more accessible and therapeutically useful information. ©2014 Wiley Periodicals, Inc.

Antithrombotic treatment for stroke prevention in atrial fibrillation: The Asian agenda.

PubMed

Chen, Chen-Huan; Chen, Mien-Cheng; Gibbs, Harry; Kwon, Sun U; Lo, Sidney; On, Young Keun; Rosman, Azhari; Suwanwela, Nijasri C; Tan, Ru San; Tirador, Louie S; Zirlik, Andreas

2015-07-15

Atrial fibrillation (AF) is the most common heart arrhythmia. Untreated AF incurs a considerable burden of stroke and associated healthcare costs. Asians have AF risk factors similar to Caucasians and a similarly increased risk of AF-related stroke; however, with a vast and rapidly ageing population, Asia bears a disproportionately large disease burden. Urgent action is warranted to avert this potential health crisis. Antithrombotic therapy with oral anticoagulants is the most effective means of preventing stroke in AF and is a particular priority in Asia given the increasing disease burden. However, AF in Asia remains undertreated. Conventional oral anticoagulation with warfarin is problematic in Asia due to suboptimal control and a propensity among Asians to warfarin-induced intracranial haemorrhage. Partly due to concerns about intracranial haemorrhage, there are considerable gaps between AF treatment guidelines and clinical practice in Asia, in particular overuse of antiplatelet agents and underuse of anticoagulants. Compared with warfarin, new direct thrombin inhibitors and Factor Xa inhibitors are non-inferior in preventing stroke and significantly reduce the risk of life-threatening bleeding, particularly intracranial bleeding. These agents may therefore provide an appropriate alternative to warfarin in Asian patients. There is considerable scope to improve stroke prevention in AF in Asia. Key priorities include: early detection of AF and identification of asymptomatic patients; assessment of stroke and bleeding risk for all AF patients; evidence-based pharmacotherapy with direct-acting oral anticoagulant agents or vitamin K antagonists for AF patients at risk of stroke; controlling hypertension; and awareness-raising, education and outreach among both physicians and patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A meta-analysis of contemporary randomized controlled trials.

PubMed

Wang, Kang-Ling; Giugliano, Robert P; Goto, Shinya; Chiu, Chun-Chih; Lin, Chun-Yi; Lai, En-Yu; Chiang, Chern-En

2016-12-01

Although randomized controlled trials (RCTs) indicated that standard dose non-vitamin K antagonist oral anticoagulants (NOACs) were more compelling, low dose NOACs are commonly used in clinical practice in Asia. The purpose of this study was to assess the relative therapeutic benefit and risk of standard dose vs low dose NOACs in Asian patients enrolled in contemporary RCTs. We performed a prespecified meta-analysis of 3155 Asian patients with NOACs in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) and ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trials. Efficacy and safety with standard dose vs low dose NOACs were compared by risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model. An evidence network incorporating additional Asian patients from ROCKET AF, J- ROCKET AF, and ARISTOTLE was constructed with the Bayesian method. Risks of stroke or systemic embolism and ischemic stroke were significantly reduced with standard dose vs low dose NOACs (RR 0.62, 95% CI 0.45-0.85; and RR 0.55, 95% CI 0.38-0.79, respectively). Rates of major, intracranial, and life-threatening bleeding with 2 dosing regimens were broadly similar (RR 1.31, 95% CI 0.74-2.33; RR 1.54, 95% CI 0.72-3.30; and RR 1.49, 95% CI 0.87-2.55, respectively). Absolute rates of all-cause mortality and the net clinical outcome with standard dose NOACs were lower but not statistically significant (absolute reduction 0.4% per year and 1.1% per year, respectively). Network meta-analyses demonstrated that standard dose NOACs had the most favorable risk-benefit profile among oral anticoagulants. In Asian patients, standard dose NOACs represent a more appealing therapeutic option than low dose NOACs, with a significant reduction in ischemic stroke without an excess of major bleeding. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

A cost-utility analysis for catheter ablation of atrial fibrillation in combination with warfarin and dabigatran based on the CHADS2 score in Japan.

PubMed

Kimura, Takehiro; Igarashi, Ataru; Ikeda, Shunya; Nakajima, Kazuaki; Kashimura, Shin; Kunitomi, Akira; Katsumata, Yoshinori; Nishiyama, Takahiko; Nishiyama, Nobuhiro; Fukumoto, Kotaro; Tanimoto, Yoko; Aizawa, Yoshiyasu; Fukuda, Keiichi; Takatsuki, Seiji

2017-01-01

We aimed to clarify the cost-effectiveness of an expensive combination therapy for atrial fibrillation (AF) using both catheter ablation and dabigatran compared with warfarin at each CHADS 2 score for patients in Japan. A Markov model was constructed to analyze costs and quality-adjusted life years associated with AF therapeutic options with a time horizon of 10 years. The target population was 60-year-old patients with paroxysmal AF. The indication for anticoagulation was determined according to the Japanese guideline. Anticoagulation-related data were derived from the RE-LY study and the AF recurrence rate was set at 2.7% per month during the first 12 months and at 0.40% per month afterwards. Stroke risk was determined according to AF recurrence, anticoagulation, and CHADS 2 score. The risks for stroke recurrence and stroke death were also considered. Costs were calculated from the healthcare payer's perspective, and only direct medical costs were included. Warfarin was the most preferred option for patients with a CHADS 2 score of 0 from a health economics aspect. Ablation under warfarin was preferred for a CHADS 2 score of 1-3, while ablation under dabigatran was preferred for a CHADS 2 score ≥4. The quality of life score for AF had the largest impact on the incremental cost-effectiveness ratios in the analysis between the anticoagulation arm and the anticoagulation+ablation arm for a CHADS 2 score of 2. Within the range of the Japanese willingness-to-pay threshold (¥5,000,000), the ablation+warfarin arm became the best option with its probability of 81.7% for a CHADS 2 score of 2; the dabigatran+ablation arm was the most preferred option with its probability of 56.1% for a CHADS 2 score of 4. Ablation under dabigatran therapy is an expensive therapeutic option, but it might benefit patients with a low quality of life and a high CHADS 2 score. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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

Major bleeding complications in patients treated with direct oral anticoagulants: One-year observational study in a Paris Hospital.

PubMed

Deville, L; Konan, M; Hij, A; Goldwirt, L; Peyrony, O; Fieux, F; Faure, P; Madelaine, I; Villiers, S; Farge-Bancel, D; Frère, C

Direct oral anticoagulants (DAOC) are indicated for the treatment of venous thromboembolism and the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. Given their advantages and friendly use for patient, the prescription of long term DOAC therapy has rapidly increased both as first line treatment while initiating anticoagulation and as a substitute to vitamins K antagonist (VKA) in poorly controlled patients. However, DOAC therapy can also be associated with significant bleeding complications, and in the absence of specific antidote at disposal, treatment of serious hemorrhagic complications under DOAC remains complex. We report and discuss herein five cases of major hemorrhagic complications under DOAC, which were reported to the pharmacological surveillance department over one year at Saint-Louis University Hospital (Paris, France). We further discuss the need for careful assessment of the risk/benefit ratio at time of starting DOAC therapy in daily clinical practice. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Use of non-vitamin K antagonist oral anticoagulants in Primary Care: ACTUA study].

PubMed

Barrios, V; Escobar, C; Lobos, J M; Polo, J; Vargas, D

2017-10-01

Approximately 40% of patients with non-valvular auricular fibrillation (NVAF) who receive vitamin K antagonists (VKA) in Primary Care in Spain have poor anticoagulation control. The objective of the study Actuación en antiCoagulación, Tratamiento y Uso de anticoagulantes orales de acción directa (ACOD) en Atención primaria (ACTUA) (Action in Coagulation, Treatment and Use of direct oral anticoagulants [DOACs]) in Primary Care) was to analyse the current situation regarding the use of VKA and non-vitamin K antagonist oral anticoagulants (NOACs) in patients with NVAF in Primary Care in Spain and the possible issues arising from it. An online survey was created covering various aspects of the use of oral anticoagulants in NAFV. A two-round modified Delphi approach was used. Results were compiled as a set of practical guidelines. Forty-four experts responded to the survey. Consensus was reached in 62% (37/60) of the items. Experts concluded that a considerable number of patients with NVAF who receive VKA do not have a well-controlled INR and that a substantial group of patients who could benefit from being treated with NOACs do not receive them. The use of NOACs increases the probability of having good anticoagulation control and decreases the risk of severe and intracranial haemorrhage. Current limitations to the use of NOACs include administrative barriers, insufficient knowledge about the benefits and risks of NOACs, limited experience of doctors in using them, and their price. Renal insufficiency influences the choice of a particular anticoagulant. The ACTUA study highlights the existing controversies about the use of oral anticoagulants for the treatment of NVAF in Primary Care in Spain, and provides consensus recommendations that may help to improve the use of these medications. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

New oral anticoagulants-TURKey (NOAC-TURK): Multicenter cross-sectional study.

PubMed

Altay, Servet; Yıldırımtürk, Özlem; Çakmak, Hüseyin Altuğ; Aşkın, Lütfü; Sinan, Ümit Yaşar; Beşli, Feyzullah; Gedikli, Ömer; Özden Tok, Özge

2017-05-01

New oral anticoagulants (NOACs) are increasingly used both for prevention of stroke in non-valvular atrial fibrillation (NVAF) and the treatment of venous thromboembolism (VTE). In this study, we aimed to evaluate the current patterns of NOACs treatment in Turkey. Moreover, demographic and clinical parameters and bleeding and/or embolic events under NOACs treatment were analyzed. The New Oral Anticoagulants-TURKey (NOAC-TURK) study was designed as a multicenter cross-sectional study. A total of 2,862 patients from 21 different centers of Turkey under the treatment of NOACs for at least three months were included in this study. Demographic, clinical, and laboratory characteristics of study participants with their medications used were obtained through the NOAC-TURK survey database. Additional necessary medical records were obtained from electronic health records of participating centers. Of the 2. 862 patients, 1.131 (39.5%) were male and the mean age was 70.3±10.2 years. Hypertension was found as the most frequent comorbidity (81%). The most common indication for NOACs was permanent atrial fibrillation (83.3%). NOACs were mainly preferred because of inadequate therapeutic range or overdose during warfarin usage. The most frequent complication was bleeding (n=217, 7.6%), and major bleeding was observed in 1.1% of the patients. Embolic events were observed in 37 patients (1.3%). Rivaroxaban and dabigatran were both more preferred than apixaban. Almost half of the patients (47.6%) were using lower doses of NOACs, which is definitely much more than expected. The NOAC-TURK study showed an important overview of the current NOACs treatment regimens in Turkey. Although embolic and bleeding complications were lower than or similar to previous studies, increased utilization of low-dose NOACs in this study should be considered carefully. According to the results of this study, NOACs treatment should be guided through CHA2DS2-VASc and HASBLED scores to ensure more benefit and less adverse effects in NVAF patients.

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.
.

Incidence, Characteristics, and Clinical Course of Device-Related Thrombus After Watchman Left Atrial Appendage Occlusion Device Implantation in Atrial Fibrillation Patients.

PubMed

Kubo, Shunsuke; Mizutani, Yukiko; Meemook, Krissada; Nakajima, Yoshifumi; Hussaini, Asma; Kar, Saibal

2017-12-11

This study investigated characteristics and clinical impact of device-related thrombus formation after Watchman device implantation in atrial fibrillation (AF) patients. Left atrial appendage occlusion using the Watchman device is an effective alternative to anticoagulation for stroke prevention in AF patients. However, device-related thrombus formation remains an important concern after Watchman implantation. From 2006 to 2014, 119 consecutive AF patients underwent Watchman implantation. Transesophageal echocardiographic (TEE) follow-up was scheduled at 45 days, at 6 months, and at 12 months after the procedure. The incidence, characteristics, and clinical course of device-related thrombus formation detected by TEE were assessed. Follow-up TEE identified thrombus formation on the Watchman device in 4 patients (3.4%). The prevalence of chronic AF was 100% in patients with thrombus, which was higher than that for patients without thrombus (40.0%). Deployed device size was numerically larger in patients with thrombus (29.3 ± 3.8 mm vs. 25.7 ± 3.2 mm, respectively). All patients with thrombus discontinued any of the anticoagulant/antiplatelet therapy which was required under the study protocol. After restarting or continuing warfarin and aspirin therapy, complete resolution of the thrombus was achieved in all patients at subsequent follow-up TEE. Warfarin therapy was discontinued within 6 months for all cases, and there was no thrombus recurrence. The mean follow-up duration was 1,456 ± 546 days, with no death, stroke, or systemic embolization events in patients with thrombus. AF burden, device size, and anticoagulant/antiplatelet regimens can be associated with device-related thrombus after Watchman device implantation. Short-term warfarin therapy was effective, and the clinical outcomes were favorable. Copyright © 2017 American College of Cardiology Foundation. All rights reserved.

Rectus Sheath Hematoma Associated with Apixaban.

PubMed

Gunasekaran, Kulothungan; Winans, Amanda R McFee; Murthi, Swetha; Ahmad, Mudassar Raees; Kaatz, Scott

2017-06-07

Apixaban is an oral anticoagulant that directly inhibits Factor Xa and is indicated for the prophylaxis and treatment of deep venous thrombosis and stroke prevention in non-valvular atrial fibrillation. Rectus sheath hematoma is a rare, life-threatening complication of anticoagulant treatment. We describe a case of an elderly patient on apixaban for the treatment of deep venous thrombosis who developed severe abdominal pain during hospitalization. Computed tomography of the abdomen revealed left rectus sheath hematoma. Apixaban was discontinued and the patient was monitored for extension of the hematoma. After 2 days she was discharged home. Outpatient computed tomography 1 month later showed complete resolution of the rectus sheath hematoma. We recommend that clinicians become aware of the potential for rare and serious bleeding complications of anticoagulants and identify the need for early recognition and prompt management.

Drug Interactions of Direct-Acting Oral Anticoagulants.

PubMed

Fitzgerald, John Leonard; Howes, Laurence Guy

2016-09-01

In recent years, new direct-acting oral anticoagulants (DOACs) have been introduced into clinical practice that specifically inhibit either factor Ia or Xa. These drugs have, to a large extent, replaced warfarin for the treatment of venous thrombosis, pulmonary embolism, and non-valvular atrial fibrillation. They have potential advantages over warfarin in providing more stable anticoagulation and the lack of a need for regular venesection to monitor activity. They also have the promise of less drug and food interactions. All of these drugs are substrates for the permeability glycoprotein (P-gp) excretion system, and several are metabolised, in part, by cytochrome P450 (CYP) 3A4. This current article assesses the interactions that do or may occur with the DOACs, particularly with respect to the P-gp and CYP3A4 systems.

Internal Medicine Physicians’ Perceptions Regarding Rate versus Rhythm Control for Atrial Fibrillation

PubMed Central

McCabe, James M.; Johnson, Colleen J; Marcus, Gregory M

2011-01-01

Atrial fibrillation (AF) is often managed by general internal medicine physicians. Available data suggest that guidelines regarding AF management are often not followed, but the reasons for this remain unknown. We sought to assess the knowledge and beliefs of internists regarding strategies to treat AF. We conducted a national electronic survey of internal medicine physicians regarding their perceptions of optimal AF management, with an emphasis on the rationale for choosing a rhythm or rate control strategy. One hundred and forty-eight physicians from 36 different states responded (representing at least 19% of unique e-mails opened). Half of the respondents reported managing their AF patients independently without referral to a cardiologist. Seventy-three percent of participants believe a rhythm control strategy conveys a decreased stroke risk, 64% believe there is a mortality benefit to rhythm control, and 55% think that it would help avoid long term anticoagulation. Comparing those who prefer a rhythm control strategy to everyone else, those who favor rhythm control statistically significantly more often believe that rhythm control reduces the risk for stroke (96% versus 67%, p=0.009) and that rhythm control allows for the discontinuation of anticoagulation therapy (76% versus 49%, p=0.045). In conclusion, contrary to available data in clinical trials and recent guidelines regarding the rationale for choosing a rhythm control strategy in treating AF, the majority of study participants believe that rhythm control decreases stroke risk, decreases mortality, and allows for discontinuation of anticoagulation therapy. These prevalent misconceptions may substantially contribute to guideline non-adherence. PMID:19195516

Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban—an oral, direct Factor Xa inhibitor

PubMed Central

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

2014-01-01

The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2–3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban. PMID:25426077

Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban-an oral, direct Factor Xa inhibitor.

PubMed

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

2014-01-01

The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2-3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban.

Non-vitamin K antagonist oral anticoagulants versus warfarin for the prevention of spontaneous echo-contrast and thrombus in patients with atrial fibrillation or flutter undergoing cardioversion: A trans-esophageal echocardiography study.

PubMed

Kim, Yun Gi; Choi, Jong-Il; Kim, Mi-Na; Cho, Dong-Hyuk; Oh, Suk-Kyu; Kook, Hyungdon; Park, Hee-Soon; Lee, Kwang No; Baek, Yong-Soo; Roh, Seung-Young; Shim, Jaemin; Park, Seong-Mi; Shim, Wan Joo; Kim, Young-Hoon

2018-01-01

Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal echocardiography (TEE) is known as a strong surrogate marker for future risk of ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is currently unknown. AF or AFL patients who underwent direct current cardioversion (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single center were analyzed. The prevalence of SEC and thrombus were compared between patients who received NOAC and those who took warfarin. NOAC included direct thrombin inhibitor and factor Xa inhibitors. Among 1,050 patients who were considered for DCCV, 424 patients anticoagulated with warfarin or NOAC underwent TEE prior to DCCV. Eighty patients who were anticoagulated for less than 21 days were excluded. Finally, 344 patients were included for the analysis (180 warfarin users vs. 164 NOAC users). No significant difference in the prevalence of SEC (44.4% vs. 43.9%; p = 0.919), dense SEC (13.9% vs. 15.2%; p = 0.722), or thrombus (2.2% vs. 4.3%; p = 0.281) was observed between the warfarin group and the NOAC group. In multivariate analysis, there was no association between NOAC and risk of SEC (odds ratio [OR]: 1.4, 95% CI: 0.796-2.297, p = 0.265) or thrombus (OR: 3.4, 95% CI: 0.726-16.039, p = 0.120). In conclusion, effectiveness of NOAC is comparable to warfarin in preventing SEC and thrombus in patients with AF or AFL undergoing DCCV. However, numerical increase in the prevalence of thrombus in NOAC group warrants further evaluation.

Non-vitamin K antagonist oral anticoagulants versus warfarin for the prevention of spontaneous echo-contrast and thrombus in patients with atrial fibrillation or flutter undergoing cardioversion: A trans-esophageal echocardiography study

PubMed Central

Kim, Yun Gi; Kim, Mi-Na; Cho, Dong-Hyuk; Oh, Suk-Kyu; Kook, Hyungdon; Park, Hee-Soon; Lee, Kwang No; Baek, Yong-Soo; Roh, Seung-Young; Shim, Jaemin; Park, Seong-Mi; Shim, Wan Joo; Kim, Young-Hoon

2018-01-01

Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal echocardiography (TEE) is known as a strong surrogate marker for future risk of ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is currently unknown. AF or AFL patients who underwent direct current cardioversion (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single center were analyzed. The prevalence of SEC and thrombus were compared between patients who received NOAC and those who took warfarin. NOAC included direct thrombin inhibitor and factor Xa inhibitors. Among 1,050 patients who were considered for DCCV, 424 patients anticoagulated with warfarin or NOAC underwent TEE prior to DCCV. Eighty patients who were anticoagulated for less than 21 days were excluded. Finally, 344 patients were included for the analysis (180 warfarin users vs. 164 NOAC users). No significant difference in the prevalence of SEC (44.4% vs. 43.9%; p = 0.919), dense SEC (13.9% vs. 15.2%; p = 0.722), or thrombus (2.2% vs. 4.3%; p = 0.281) was observed between the warfarin group and the NOAC group. In multivariate analysis, there was no association between NOAC and risk of SEC (odds ratio [OR]: 1.4, 95% CI: 0.796–2.297, p = 0.265) or thrombus (OR: 3.4, 95% CI: 0.726–16.039, p = 0.120). In conclusion, effectiveness of NOAC is comparable to warfarin in preventing SEC and thrombus in patients with AF or AFL undergoing DCCV. However, numerical increase in the prevalence of thrombus in NOAC group warrants further evaluation. PMID:29360845

Adoption of direct oral anticoagulants for stroke prevention in atrial fibrillation.

PubMed

Baker, D; Wilsmore, B; Narasimhan, S

2016-07-01

Direct oral anticoagulants (DOAC) are being increasingly utilised for stroke prevention in atrial fibrillation (AF) and atrial flutter. To analyse the adoption and application of these drugs in a regional hospital inpatient cohort and compare with national prescribing data. Digital medical records identified prescribed anticoagulants for patients admitted with AF and atrial flutter during 2013-2014. Analysis of patient demographics and stroke risk identified trends in prescribing DOAC versus warfarin. For broader comparison, data from the Pharmaceuticals Benefits Scheme were sourced to determine the nation-wide adoption of DOAC. Of the 615 patients identified, 505 (255 in 2013, 250 in 2014) had sufficient records to include in the study. From 2013 to 2014, DOAC prescriptions increased from 9 to 28% (P < 0.001), warfarin and aspirin remained comparatively stable (38-34%, 22-20%), and those prescribed no medication declined (17-8%, P < 0.001). DOAC were prescribed to patients with lower CHA2 DS2 VASc scores than warfarin (3.6 vs 4.4; P = 0.005), lower HAS-BLED scores (1.7 vs 2.3; P < 0.01), higher glomerular filtration rates; 70 vs 63 ml/min; P = 0.002) and younger age (74 vs 77 years; P = 0.006). Nationally, warfarin prescriptions are higher in total numbers but increasing at a slower rate than DOAC, which increased 10-fold (101 158 in 2013, 1 095 985 in 2014). DOAC prescribing grew rapidly from 2013 to 2014, regionally and nationally. Warfarin prescriptions have remained stable, indicating that more patients are being appropriately anticoagulated for AF who previously were not. DOAC were found to be prescribed to patients with lower CHA2 DS2 VASc and HAS-BLED scores, younger age and higher glomerular filtration rates. Aspirin therapy remains over utilised in AF. © 2016 Royal Australasian College of Physicians.

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.

Antithrombotic therapy in atrial fibrillation: aspirin is rarely the right choice

PubMed Central

Sabir, Ian N; Matthews, Gareth D K; Huang, Christopher L-H

2013-01-01

Atrial fibrillation, the commonest cardiac arrhythmia, predisposes to thrombus formation and consequently increases risk of ischaemic stroke. Recent years have seen approval of a number of novel oral anticoagulants. Nevertheless, warfarin and aspirin remain the mainstays of therapy. It is widely appreciated that both these agents increase the likelihood of bleeding: there is a popular conception that this risk is greater with warfarin. In fact, well-managed warfarin therapy (INR 2-3) has little effect on bleeding risk and is twice as effective as aspirin at preventing stroke. Patients with atrial fibrillation and a further risk factor for stroke (CHA2DS2-VASc >0) should therefore either receive warfarin or a novel oral agent. The remainder who are at the very lowest risk of stroke are better not prescribed antithrombotic therapy. For stroke prevention in atrial fibrillation; aspirin is rarely the right choice. PMID:23404744

Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review.

PubMed

Violi, Francesco; Lip, Gregory Yh; Pignatelli, Pasquale; Pastori, Daniele

2016-03-01

Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables.The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs.Data sources are MEDLINE via PubMed and Cochrane database.All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone.We performed a systematic review of the literature up to October 2015, searching for a combination of "food," "diet," "vitamin K," "phylloquinone," "warfarin," "INR," "coagulation," and "anticoagulant."Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 μg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 μg/day).Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable.The available evidence does not support current advice to modify dietary habits when starting therapy with VKAs. Restriction of dietary vitamin K intake does not seem to be a valid strategy to improve anticoagulation quality with VKAs. It would be, perhaps, more relevant to maintain stable dietary habit, avoiding wide changes in the intake of vitamin K.

Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial.

PubMed

Åsberg, Signild; Hijazi, Ziad; Norrving, Bo; Terént, Andreas; Öhagen, Patrik; Oldgren, Jonas

2017-12-02

Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design are combined with the strengths of a national clinical quality register in allowing simplified enrolment and follow-up of study patients. In addition, the register adds the possibility of directly assessing the external validity of the study findings. ClinicalTrials.gov, NCT02961348 . Registered on 8 November 2016.

Kidney function monitoring and nonvitamin K oral anticoagulant dosage in atrial fibrillation.

PubMed

Andreu Cayuelas, Jose Manuel; Caro Martínez, Cesar; Flores Blanco, Pedro Jose; Elvira Ruiz, Gines; Albendin Iglesias, Helena; Cerezo Manchado, Juan Jose; Bailen Lorenzo, Jose Luis; Januzzi, James L; García Alberola, Arcadio; Manzano-Fernández, Sergio

2018-06-01

Clinical practice guidelines recommend regular kidney function monitoring in atrial fibrillation patients on nonvitamin K oral anticoagulants (NOAC); however, information regarding compliance with these recommendations in daily life conditions is scarce. We sought to determine the compliance with kidney function monitoring recommendations in nonvalvular atrial fibrillation (NVAF) patients starting NOAC and its implication on the appropriateness of NOAC dosage. This study involves the retrospective analysis of a multicentre registry including consecutive NVAF patients who started NOAC (n = 692). Drug dosage changes and serum creatinine determinations were recorded during 1-year follow-up. European Heart Rhythm Association criteria were used to define the appropriateness of kidney function monitoring as well as adequate NOAC dosage. During the follow-up (334 ± 89 days), the compliance with kidney function monitoring recommendations was 61% (n = 425). After multivariate adjustment, age (OR × year: 0.92 (CI 95%: 0.89-0.95) P < .001), creatinine clearance (OR × mL/min: 1.02 (CI 95%: 1.01-1.03) P < .001) and adequate NOAC dosage at baseline (OR: 1.54 (CI 95%: 1.06-2.23), P = .024) were independent predictors of appropriate kidney function monitoring. Compliance with kidney function monitoring recommendations was independently associated with change to appropriate NOAC dose after 1 year (OR: 2.80 (CI 95%: 1.01-7.80), P = .049). Noncompliance with kidney function monitoring recommendations is common in NVAF patients starting NOAC, especially in elderly patients with kidney dysfunction. Compliance with kidney function monitoring recommendations was associated with adequate NOAC dosage at 1-year follow-up. Further studies are warranted to evaluate the implication of kidney function monitoring on prognosis. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES

PubMed Central

Hanna, Michael S; Mohan, Puneet; Knabb, Robert; Gupta, Elora; Frost, Charles; Lawrence, John H

2014-01-01

The factor Xa inhibitor apixaban is one of the novel anticoagulants to emerge as alternatives to long-standing standards of care that include low-molecular-weight heparin and warfarin. The development of apixaban reflects a strategy to optimize the clinical pharmacology profile, dosing posology, trial designs, and statistical analyses across multiple indications, and to seek alignment with global health authorities. The primary objective of dose selection was to maintain balance between efficacy and bleeding risk. Twice-daily dosing of apixaban, rather than once daily, was chosen to lower peak concentrations and reduce fluctuations between peak and trough levels. Our discussion here focuses on the use of apixaban for stroke prevention in nonvalvular atrial fibrillation (NVAF). Supporting this indication, a pair of registrational trials was conducted that enrolled the full spectrum of patients who, by guidelines, were eligible for anticoagulation. In the AVERROES study of patients who were unsuitable for warfarin therapy, apixaban was superior to aspirin in reducing the risk of stroke or systemic embolism (SSE), without a significant increase in major bleeding (MB). In the ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) study, apixaban was superior to warfarin on the rates of SSE, MB, and all-cause mortality. Overall, these studies have demonstrated a substantially favorable benefit–risk profile for apixaban over warfarin and aspirin in NVAF. PMID:25377080

Impact of the Health Insurance Coverage Policy on Oral Anticoagulant Prescription among Patients with Atrial Fibrillation in Korea from 2014 to 2016.

PubMed

Ko, Young-Jin; Kim, Seonji; Park, Kyounghoon; Kim, Minsuk; Yang, Bo Ram; Kim, Mi-Sook; Lee, Joongyub; Park, Byung-Joo

2018-06-04

To evaluate oral anticoagulant (OAC) utilization in patients with atrial fibrillation after the changes in the health insurance coverage policy in July 2015. We used the Health Insurance Review and Assessment Service-National Patient Samples (HIRA-NPS) between 2014 and 2016. The HIRA-NPS, including approximately 1.4 million individuals, is a stratified random sample of 3% of the entire Korean population using 16 age groups and 2 sex groups. The HIRA-NPS comprises personal and medical information such as surgical or medical treatment provided, diagnoses, age, sex, region of medical institution, and clinician characteristics. The studied drugs included non-vitamin K antagonist OACs (NOACs) such as apixaban, dabigatran, edoxaban, and rivaroxaban, and were compared with warfarin. We analyzed drug utilization pattern under three aspects: person, time, and place. The number of patients with atrial fibrillation who were prescribed OACs was 3,114, 3,954, and 4,828; and the proportions of prescribed NOACs to total OACs were 5.1%, 36.2%, and 60.8% in 2014, 2015, and 2016, respectively. The growth rate of OACs prescription increased from 61.4 patients/quarter before June 2015 to 147.7 patients/quarter thereafter. These changes were predominantly in elderly individuals aged more than 70 years. The proportion of NOACs to OACs showed significant regional difference. The change of health insurance coverage policy substantially influenced OACs prescription pattern in whole Korean region. But the impact has been significantly different among regions and age groups, which provides the evidence for developing standard clinical practice guideline on OACs use.

Short-Term Heparin Kinetics during Catheter Ablation of Atrial Fibrillation.

PubMed

Gabus, Vincent; Rollin, Anne; Maury, Philippe; Forclaz, Andrei; Pascale, Patrizio; Dhutia, Harshil; Bisch, Laurence; Pruvot, Etienne

2015-10-01

Percutaneous catheter ablation of atrial fibrillation (CA-AF) is a treatment option for symptomatic drug-refractory atrial fibrillation (AF). CA-AF carries a risk for thromboembolic complications that has been minimized by the use of intraprocedural intravenous unfractionated heparin (UFH). The optimal administration of UFH as well as its kinetics are not well established and need to be precisely determined. A total 102 of consecutive patients suffering from symptomatic drug-refractory AF underwent CA-AF. The mean age was 61 ± 10 years old. After transseptal puncture of the fossa ovalis, weight-adjusted UFH bolus (100 U/kg) was infused. A significant increase in activated clotting time (ACT) was observed from an average value of 100 ± 27 seconds at baseline, to 355 ± 94 seconds at 10 min (T10), to 375 ± 90 seconds at 20 min (T20). Twenty-four patients failed to reach the targeted ACT value of ≥300 seconds at T10 and more than half of these remained with subtherapeutic ACT values at T20. This subset of patients showed similar clinical characteristics and amount of UFH but were more frequently prescribed preprocedural vitamin K1 than the rest of the study population. In a typical intervention setting, UFH displays unexpected slow anticoagulation kinetics in a significant proportion of procedures up to 20 minutes after infusion. These findings support the infusion of UFH before transseptal puncture or any left-sided catheterization with early ACT measurements to identify patients with delayed kinetics. They are in line with recent guidelines to perform CA-AF under therapeutic anticoagulation. © 2015 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

Health status, geriatric syndromes and prescription of oral anticoagulant therapy in elderly medical inpatients with atrial fibrillation.

PubMed

Bo, Mario; Sciarrillo, Irene; Maggiani, Guido; Falcone, Yolanda; Iacovino, Marina; Grisoglio, Enrica; Fonte, Gianfranco; Grosjean, Simon; Gaita, Fiorenzo

2017-03-01

The aim of the present study was to investigate the prevalence of geriatric syndromes among older medical inpatients with atrial fibrillation, and their association with use of vitamin K antagonists. A retrospective study of patients aged ≥65 years discharged with a diagnosis of atrial fibrillation from the Acute Geriatric Ward was carried out. Stroke and bleeding risk were evaluated according to the CHA 2 DS 2 -VASC and HAS-BLED scores. Comorbidity, cognitive status, functional autonomy and contraindications to vitamin K antagonists were also considered. Atrial fibrillation was documented in 1078 of 3650 patients (29.5%, mean age 83.4 ± 6.6 years, 60.3% women). Contraindications to vitamin K antagonists were documented in 24.9% of patients. Prescription of vitamin K antagonists at discharge was 37.8% and 47.9%, in the overall sample and in those without contraindications, respectively. In the overall sample, prescription of vitamin K antagonists was associated with younger age, permanent/persistent atrial fibrillation, home discharge, less comorbidity, higher hemoglobin levels, better functional independence, known atrial fibrillation at admission and lower HAS-BLED score. Among patients without contraindications to vitamin K antagonists, their use at discharge was independently associated with younger age, permanent/persistent atrial fibrillation, home discharge, higher hemoglobin levels and CHA2DS2-VASC score, better functional autonomy, and greater number of drugs. We showed a high prevalence of atrial fibrillation among older medical inpatients, who have a poor health status and a high prevalence of geriatric syndromes. Vitamin K antagonists were prescribed in less than half of the patients; underuse was mainly accounted for by a high prevalence of comorbidities/contraindications, poor health status and limited functional autonomy. Geriatr Gerontol Int 2017; 17: 416-423. © 2016 Japan Geriatrics Society.

Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation

PubMed Central

Camm, A. John; Pinto, Fausto J.; Hankey, Graeme J.; Andreotti, Felicita; Hobbs, F.D. Richard

2015-01-01

Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers. PMID:26116685

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.

Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

PubMed

Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

2017-01-01

Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r 2  = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r 2  = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: Data From ROCKET AF.

PubMed

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

2016-03-08

Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. 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) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS2 score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P<0.0001) were associated with higher all-cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C-index 0.677). In a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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.

Effect of the Size of the Left Atrium on Sustained Sinus Rhythm in Patients Undergoing Mitral Valve Surgery and Concomitant Bipolar Radiofrequency Ablation for Atrial Fibrillation.

PubMed

Avdagić, Harun; Sijerčić Avdagić, Selma; Pirić Avdagić, Melika; Antonič, Miha

2017-12-01

Atrial fibrillation is associated with systemic embolization and complications due to anticoagulant therapy. Radiofrequency ablation has been established as an effective and safe method for the treatment of atrial fibrillation. The aim of this study was to evaluate the effect of the size of the left atrium on the outcome of surgical radiofrequency ablation. Forty patients scheduled for elective mitral valve surgery and radiofrequency ablation were enrolled in the study. Group 1 consisted of patients with a left atrium diameter ≤5 cm and group 2 of patients with left atrium diameter >5 cm. The primary endpoint of the study was stable sinus rhythm 6 months postoperatively. At 6 months postoperatively, sinus rhythm was present in significantly more group 1 patients as compared with group 2 patients, i.e. 15 (75%) vs. 8 (40%), p=0.025. Multivariate analysis proved the size of the left atrium to be an independent predictor of the radiofrequency ablation outcome. Accordingly, the size of the left atrium was demonstrated to be an important predictor of the outcome of radiofrequency ablation for atrial fibrillation. A lower cut-off value of surgical reduction of the atria than previously reported should be considered in order to improve the radiofrequency ablation outcome.

Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis.

PubMed

Xu, Wei-Wei; Hu, Shen-Jiang; Wu, Tao

2017-07-01

Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs. We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods. Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg). Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.

Costs of major intracranial, gastrointestinal and other bleeding events in patients with atrial fibrillation - a nationwide cohort study.

PubMed

Jakobsen, Marie; Kolodziejczyk, Christophe; Klausen Fredslund, Eskild; Poulsen, Peter Bo; Dybro, Lars; Paaske Johnsen, Søren

2017-06-12

Use of oral anticoagulation therapy in patients with atrial fibrillation (AF) involves a trade-off between a reduced risk of ischemic stroke and an increased risk of bleeding events. Different anticoagulation therapies have different safety profiles and data on the societal costs of both ischemic stroke and bleeding events are necessary for assessing the cost-effectiveness and budgetary impact of different treatment options. To our knowledge, no previous studies have estimated the societal costs of bleeding events in patients with AF. The objective of this study was to estimate the 3-years societal costs of first-incident intracranial, gastrointestinal and other major bleeding events in Danish patients with AF. The study was an incidence-based cost-of-illness study carried out from a societal perspective and based on data from national Danish registries covering the period 2002-2012. Costs were estimated using a propensity score matching and multivariable regression analysis (first difference OLS) in a cohort design. Average 3-years societal costs attributable to intracranial, gastrointestinal and other major bleeding events were 27,627, 17,868, and 12,384 EUR per patient, respectively (2015 prices). Existing evidence shows that the corresponding costs of ischemic stroke were 24,084 EUR per patient (2012 prices). The average costs of bleeding events did not differ between patients with AF who were on oral anticoagulation therapy prior to the event and patients who were not. The societal costs attributable to major bleeding events in patients with AF are significant. Intracranial haemorrhages are most costly to society with average costs of similar magnitude as the costs of ischemic stroke. The average costs of gastrointestinal and other major bleeding events are lower than the costs of intracranial haemorrhages, but still substantial. Knowledge about the relative size of the costs of bleeding events compared to ischemic stroke in patients with AF constitutes valuable evidence for decisions-makers in Denmark as well as in other countries.

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.

Clinician time used for decision making: a best case workflow study using cardiovascular risk assessments and Ask Mayo Expert algorithmic care process models.

PubMed

North, Frederick; Fox, Samuel; Chaudhry, Rajeev

2016-07-20

Risk calculation is increasingly used in lipid management, congestive heart failure, and atrial fibrillation. The risk scores are then used for decisions about statin use, anticoagulation, and implantable defibrillator use. Calculating risks for patients and making decisions based on these risks is often done at the point of care and is an additional time burden for clinicians that can be decreased by automating the tasks and using clinical decision-making support. Using Morae Recorder software, we timed 30 healthcare providers tasked with calculating the overall risk of cardiovascular events, sudden death in heart failure, and thrombotic event risk in atrial fibrillation. Risk calculators used were the American College of Cardiology Atherosclerotic Cardiovascular Disease risk calculator (AHA-ASCVD risk), Seattle Heart Failure Model (SHFM risk), and CHA2DS2VASc. We also timed the 30 providers using Ask Mayo Expert care process models for lipid management, heart failure management, and atrial fibrillation management based on the calculated risk scores. We used the Mayo Clinic primary care panel to estimate time for calculating an entire panel risk. Mean provider times to complete the CHA2DS2VASc, AHA-ASCVD risk, and SHFM were 36, 45, and 171 s respectively. For decision making about atrial fibrillation, lipids, and heart failure, the mean times (including risk calculations) were 85, 110, and 347 s respectively. Even under best case circumstances, providers take a significant amount of time to complete risk assessments. For a complete panel of patients this can lead to hours of time required to make decisions about prescribing statins, use of anticoagulation, and medications for heart failure. Informatics solutions are needed to capture data in the medical record and serve up automatically calculated risk assessments to physicians and other providers at the point of care.

Clinical and Economic Implications of Apixaban Versus Aspirin in the Low-Risk Nonvalvular Atrial Fibrillation Patients.

PubMed

Lip, Gregory Y H; Lanitis, Tereza; Mardekian, Jack; Kongnakorn, Thitima; Phatak, Hemant; Dorian, Paul

2015-10-01

Although recommended by guidelines, the benefits of treating patients with atrial fibrillation with a low-stroke risk score, with aspirin or anticoagulants, have not been clearly established. With advent of safer non-vitamin K antagonist oral anticoagulant, we assessed the clinical and economic implications of 5 mg BID of apixaban versus aspirin among patients with a relative low risk of stroke as assessed using the CHADS2 (congestive heart failure, hypertension, age>75, diabetes mellitus, stroke/transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke/transient ischemic attack, vascular disease) stroke risk classification. A previously developed and validated Markov model was adapted. A secondary analysis of the Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study was conducted to estimate event rates in different low-risk cohorts by treatment. Three cohorts (n=1000) with a CHADS2 score of 1, CHA2DS2-VASc score of 1, and CHA2DS2-VASc of score 2 to 4 were simulated to assess the number of clinical events avoided in terms of strokes and major bleeds, as well as life years gained, quality-adjusted life years gained, costs, and incremental costs per quality-adjusted life year gained. Apixaban was associated with fewer strokes and systemic embolism versus aspirin across all subgroups; however, it caused more major bleeding events. The reduction in systemic embolism offset the increase in major bleeding events leading to increased life expectancy and quality-adjusted life year gains, achieved at an increased cost that was lower than the UK threshold of $44,400 (ie, £30,000) per quality-adjusted life year gained across the 3 cohorts examined. Anticoagulant treatment with apixaban versus aspirin in low-risk patients, as identified using CHADS2 or CHA2DS2-VASc, is projected to increase life expectancy and provide clinical benefits that are cost effective. © 2015 American Heart Association, Inc.

[Atrial fibrillation in elderly].

PubMed

Arquizan, Caroline

2012-11-01

Atrial fibrilation (AF) is frequent and a strong risk factor for ischemic stroke in elderly. Ischemic stroke in patients with AF are more severe. Vitamine K antagonist therapy is highly effective for stroke prevention but is associated with hemorrhagic risk. The new oral anticoagulants (direct thrombin inhibitor [dabigatran], and direct factor Xa inhibitors [rivaroxaban and apixaban]) have all shown non inferiority or superiority, with better safety, considering the risk of intracranial haemorrhage. On this basis, it is justified to give them in priority in the vast majority of patients with AF, the choice of the drug and the dose is individual.

Retroperitoneal haematoma in a postoperative ALIF patient taking rivaroxaban for atrial fibrillation.

PubMed

Deekonda, Praveena; Stokes, Oliver M; Chan, Daniel

2016-11-02

Novel oral anticoagulants (NOACs) are being increasingly used in the secondary prevention of thromboembolic stroke in patients with atrial fibrillation. Patients taking NOACs are difficult to manage perioperatively, and several unexpected complications have been reported in these patients. We report a case of a rivaroxaban-induced retroperitoneal haematoma in a 72-year-old man who underwent an L5/S1 anterior lumbar interbody fusion (ALIF) for grade 1 spondylolytic spondylolisthesis. The patient suffered from atrial fibrillation and was taking rivaroxaban, a factor Xa inhibitor, for thromboembolic risk reduction. In accordance with perioperative Novel Oral Anticoagulant (NOAC) guidelines, rivaroxaban was stopped 2 days preoperatively and restarted on the third postoperative day. The patient presented on the ninth postoperative day, complaining of severe left iliac fossa pain, nausea, and vomiting, accompanied by swelling and bruising around the surgical site. A computed tomography (CT) scan showed a large expanding retroperitoneal haematoma. The patient was taken back to theatre for an evacuation of the haematoma and subsequently recovered without any further complications. This is the first case of a rivaroxaban-induced retroperitoneal haematoma reported in the literature, secondary to elective spinal surgery. This report adds to the body of evidence on the risk of postoperative bleeding in patients taking NOACs. If patients on NOACs present with abdominal symptoms following anterior approach to the lumbar spine, treating clinicians should have a high index of suspicion for retroperitoneal haematoma.

Canadian Cardiovascular Society atrial fibrillation guidelines 2010: prevention and treatment of atrial fibrillation following cardiac surgery.

PubMed

Mitchell, L Brent

2011-01-01

Postoperative atrial fibrillation and atrial flutter (POAF) are the most common complications of cardiac surgery that require intervention or prolong intensive care unit and total hospital stay. For some patients, these tachyarrhythmias have important consequences including patient discomfort/anxiety, hemodynamic deterioration, cognitive impairment, thromboembolic events including stroke, exposure to the risks of antiarrhythmic treatments, longer hospital stay, and increased health care costs. We conclude that prevention of POAF is a worthwhile exercise and recommend that the dominant therapy for this purpose be β-blocker therapy, especially the continuation of β-blocker therapy that is already in place. When β-blocker therapy is contraindicated, amiodarone prophylaxis is recommended. If both of these therapies are contraindicated, therapy with either intravenous magnesium or biatrial pacing is suggested. Patients at high risk of POAF may be considered for first-line amiodarone therapy, first-line sotalol therapy, or combination prophylactic therapy. The treatment of POAF may follow either a rate-control approach (with the dominant therapy being β-blocking drugs) or a rhythm-control approach. Anticoagulation should be considered if persistent POAF lasts >72 hours and at the point of hospital discharge. The ongoing need for any POAF treatment (including anticoagulation) should be reconsidered 6-12 weeks after the surgical procedure. Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Evaluation of the predictive performance of bleeding risk scores in patients with non-valvular atrial fibrillation on oral anticoagulants.

PubMed

Beshir, S A; Aziz, Z; Yap, L B; Chee, K H; Lo, Y L

2018-04-01

Bleeding risk scores (BRSs) aid in the assessment of oral anticoagulant-related bleeding risk in patients with atrial fibrillation. Ideally, the applicability of a BRS needs to be assessed, prior to its routine use in a population other than the original derivation cohort. Therefore, we evaluated the performance of 6 established BRSs to predict major or clinically relevant bleeding (CRB) events associated with the use of oral anticoagulant (OAC) among Malaysian patients. The pharmacy supply database and the medical records of patients with non-valvular atrial fibrillation (NVAF) receiving warfarin, dabigatran or rivaroxaban at two tertiary hospitals were reviewed. Patients who experienced an OAC-associated major or CRB event within 12 months of follow-up, or who have received OAC therapy for at least 1 year, were identified. The BRSs were fitted separately into patient data. The discrimination and the calibration of these BRSs as well as the factors associated with bleeding events were then assessed. A total of 1017 patients with at least 1-year follow-up period, or those who developed a bleeding event within 1 year of OAC use, were recruited. Of which, 23 patients experienced a first major bleeding event, whereas 76 patients, a first CRB event. Multivariate logistic regression results show that age of 75 or older, prior bleeding and male gender are associated with major bleeding events. On the other hand, prior gastrointestinal bleeding, a haematocrit value of less than 30% and renal impairment are independent predictors of CRB events. All the BRSs show a satisfactory calibration for major and CRB events. Among these BRSs, only HEMORR 2 HAGES (C-statistic = 0.71, 95% CI 0.60-0.82, P < .001) and ATRIA score (C-statistic = 0.70, 95% CI 0.58-0.82, P < .001) show acceptable discrimination performance for major bleeding events. All the 6 BRSs, however, lack acceptable predictive performance for CRB events. To the best of our knowledge, this is the first evaluation study of the predictive performance of these 6 BRSs on clinically relevant bleeding events applied to the same cohort consisting of mainly Asian novel oral anticoagulant users. These BRSs show poor to acceptable predictive performance on OAC-induced major or CRB events. An improvement in the existing BRSs for OAC users is warranted. © 2017 John Wiley & Sons Ltd.

Unnecessary overuse. Study of "inadvisable practices" for patients with atrial fibrillation.

PubMed

Ortiz, M M; Llamas, P; Sanmartín, M; Egido, J A; Del Toro, J; Egocheaga, M I; Estévez, M S; Navarro, I M; Mira, J J

2017-05-01

To identify overuse (diagnostic, therapeutic and self-care practices that represent risks that outweigh the potential benefits) in patients with atrial fibrillation. The study was based on qualitative research techniques. Using the "Metaplan" technique, we identified and ordered potentially inappropriate, ineffective and inefficient practices. By means of a consensus conference, we then established a number of "inadvisable practice" measures (relatively common practices that should be eliminated based on the scientific evidence or clinical experience). Professionals from the specialties of cardiology, haematology, neurology, internal medicine, family medicine and nursing participated in the consensus. We developed a catalogue of 19 "inadvisable practices" related to the diagnosis, treatment and care of anticoagulated patients that were inappropriate, had questionable effectiveness or were ineffective, as well as 13 beliefs or behaviours for anticoagulated patients that could result in injury or were useless or inefficient. The "inadvisable practices" approach helps identify practices that represent greater risks than benefits for patients. It seems appropriate to include algorithms in the clinical decision-making support systems that consider this information for the diagnosis, treatment and for home care. For this last case, recommendations have also been prepared that define specific contents for the healthcare education of these patients. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Controversies regarding the new oral anticoagulants for stroke prevention in patients with atrial fibrillation.

PubMed

Mohanty, Bibhu D; Looser, Patrick M; Gokanapudy, Lakshmi R; Handa, Rishi; Mohanty, Sudipta; Choi, Sharon S; Goldman, Martin E; Fuster, Valentin; Halperin, Jonathan L

2014-06-01

Increasing use of the new oral anticoagulants (NOACs) - dabigatran, rivaroxaban, and apixaban - has prompted considerable discussion in the medical community even as warfarin remains the mainstay of therapy. This article raises 10 controversial issues regarding the use of NOACs for stroke prevention in patients with atrial fibrillation, and offers a review of the latest available evidence. We provide a brief overview of the mechanism and dosing of these drugs, as well as a summary of the key clinical trials that have brought them into the spotlight. Comparative considerations relative to warfarin such as NOAC safety, efficacy, bleeding risk, reversibility, drug-transitioning and use in patients well controlled on warfarin are addressed. Use in select populations such as the elderly, those with coronary disease, renal impairment, or on multiple anti-platelet drugs is also discussed. Finally, we consider such specific issues as comparative efficacy, off-label use, cost, rebound and management during events. Ultimately, the rise of the NOACs to mainstream use will depend on further data and clinical experience amongst the medical community. © The Author(s) 2014.

Suboptimal Anticoagulant Management in Japanese Patients with Nonvalvular Atrial Fibrillation Receiving Warfarin for Stroke Prevention.

PubMed

Hirano, Teruyuki; Kaneko, Hirokazu; Mishina, Sari; Wang, Feng; Morita, Satoshi

2017-10-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with increasing prevalence in Japan. Although prothrombin time-international normalized ratio (PT-INR) targets for monitoring warfarin therapy in patients with nonvalvular AF (NVAF) are well defined, real-world patient characteristics and PT-INR levels remain unknown among Japanese patients with NVAF who initiate and continue warfarin (warfarin maintainers) versus those who switch from warfarin to direct oral anticoagulants (DOACs; warfarin switchers). Patients with NVAF receiving oral anticoagulants between February 2013 and June 2015 were identified using a nationwide electronic medical record (EMR) database from 69 hospitals in Japan. Demographics and characteristics of patients, PT-INR, time in therapeutic range (TTR), and frequency in range (FIR) of PT-INR between warfarin maintainers and warfarin switchers were assessed. A total of 1705 patients met inclusion criteria and were examined (1501 warfarin maintainers versus 204 warfarin switchers). CHADS 2 , CHA 2 DS 2 -VASc, and HAS-BLED scores were comparable between groups. However, these scores were significantly higher among warfarin switchers at the time of switching than at the time of warfarin initiation. Furthermore, TTR and FIR of PT-INR were lower in warfarin switchers than in maintainers. Nevertheless, TTR and FIR were below 50% (PT-INR, 1.6-2.6) in both patient groups. In this EMR-based clinical study, patients who switched to DOACs had both poor or inadequate PT-INR control and higher risk factors of stroke. Many patients receiving warfarin did not achieve sufficient PT-INR therapeutic range. DOACs could be recommended in Japanese patients with NVAF with inadequate PT-INR control and increased risk of stroke. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score

PubMed Central

Hijazi, Ziad; Oldgren, Jonas; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Held, Claes; Hylek, Elaine M; Lopes, Renato D; Yusuf, Salim; Granger, Christopher B; Siegbahn, Agneta; Wallentin, Lars

2018-01-01

Abstract Aims In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers. Methods and results The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score. Conclusion A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF. ClinicalTrials.gov identifier NCT00412984 and NCT00262600 PMID:29069359

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

Enoxaparin-induced spontaneous massive retroperitoneal hematoma with fatal outcome.

PubMed

Salemis, Nikolaos S; Oikonomakis, Ioannis; Lagoudianakis, Emanuel; Boubousis, Georgios; Tsakalakis, Christos; Sourlas, Sotirios; Gourgiotis, Stavros

2014-12-01

Spontaneous retroperitoneal hematoma (SRH) is a severe and potentially fatal complication of anticoagulation therapy. We describe a case of fatal spontaneous massive retroperitoneal hematoma in a female patient receiving bridging therapy with enoxaparin for atrial fibrillation. Physicians should be cautious when prescribing enoxaparin in elderly patients, in patients with impaired renal function, and in patients receiving concomitant oral anticoagulants. Emergency physicians should always consider SRH in the differential diagnosis in patients under enoxaparin therapy presenting with abdominal pain. Computed tomographic scan is the imaging modality of choice for evaluating SRH. Early diagnosis and aggressive treatment are of paramount importance as SRH is associated with high mortality and morbidity rates.

Fatal association of mechanical valve thrombosis with dabigatran: a report of two cases.

PubMed

Atar, Shaul; Wishniak, Alice; Shturman, Alexander; Shtiwi, Sewaed; Brezins, Marc

2013-07-01

Several new oral anticoagulants have been approved for thromboembolism prevention in patients with nonvalvular atrial fibrillation. However, they are not yet approved for anticoagulation use in patients with prosthetic mechanical valves, and no randomized data have been published so far on their safety of use in these patients. We present two cases of patients with prosthetic mechanical mitral valves who were switched from warfarin and acenocoumarol to dabigatran and within 1 month experienced severe valve complications resulting in death. One patient experienced stroke and later cardiogenic shock and death, and the other experienced pulmonary edema, cardiogenic shock, and subsequent death.

Analysis of antithrombotic therapy after cardioembolic stroke due to atrial fibrillation or flutter.

PubMed

Peterson, Evan J; Reaves, Anne B; Smith, Jennifer L; Oliphant, Carrie S

2013-02-01

Guidelines recommend that all patients with atrial fibrillation and a history of ischemic stroke should receive an anticoagulant. Prior analyses show that warfarin is underutilized in most populations. To examine the use of antithrombotic and anticoagulant therapy in patients with atrial fibrillation or flutter during the index hospitalization for acute, ischemic stroke. Retrospective electronic medical record review of 200 patients treated at a tertiary care hospital with a primary ICD-9 code for ischemic stroke and a secondary ICD-9 code for atrial fibrillation or flutter. Exclusion criteria were active bleeding, pregnancy, age less than 18, pre-existing warfarin allergy, or dabigatran use. Fifty-two percent of patients received at least one dose of warfarin during the index hospitalization. There was no relationship between CHADS2 score and likelihood of receiving warfarin (P > .05). There was no significant difference in adverse event rate in patients receiving warfarin compared to those receiving aspirin (3.8% vs 9.1%; P = .14), but the rate of hemorrhagic transformation was lower in patients receiving warfarin (1% vs 7%; P = .03). The composite of hemorrhagic stroke or hemorrhagic transformation was significantly lower in patients receiving bridging therapy (0% vs 11%; P = .03). Sixteen patients were readmitted for stroke within 3 months of discharge. Ten were readmitted for ischemic stroke, 3 for hemorrhagic stroke or hemorrhagic transformation, and 3 for systemic bleeding. Ten patients (62.5%) were receiving warfarin at readmission, but only one of these patients had a therapeutic INR. Warfarin was underutilized as secondary stroke prophylaxis in these high-risk patients. Bridging therapy appeared to be safe and was not associated with an increase in adverse events.

The predictive ability of the CHADS2 and CHA2DS2-VASc scores for bleeding risk in atrial fibrillation: the MAQI(2) experience.

PubMed

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

2014-08-01

Guidelines recommend the assessment of stroke and bleeding risk before initiating warfarin anticoagulation in patients with atrial fibrillation. Many of the elements used to predict stroke also overlap with bleeding risk in atrial fibrillation patients and it is tempting to use stroke risk scores to efficiently estimate bleeding risk. Comparison of stroke risk scores to bleeding risk scores to predict bleeding has not been thoroughly assessed. 2600 patients followed at seven anticoagulation clinics were followed from October 2009-May 2013. Five risk models (CHADS2, CHA2DS2-VASc, HEMORR2HAGES, HAS-BLED and ATRIA) were retrospectively applied to each patient. The primary outcome was the first major bleeding event. Area under the ROC curves were compared with C statistic and net reclassification improvement (NRI) analysis was performed. 110 patients experienced a major bleeding event in 2581.6 patient-years (4.5%/year). Mean follow up was 1.0±0.8years. All of the formal bleeding risk scores had a modest predictive value for first major bleeding events (C statistic 0.66-0.69), performing better than CHADS2 and CHA2DS2-VASc scores (C statistic difference 0.10 - 0.16). NRI analysis demonstrated a 52-69% and 47-64% improvement of the formal bleeding risk scores over the CHADS2 score and CHA2DS2-VASc score, respectively. The CHADS2 and CHA2DS2-VASc scores did not perform as well as formal bleeding risk scores for prediction of major bleeding in non-valvular atrial fibrillation patients treated with warfarin. All three bleeding risk scores (HAS-BLED, ATRIA and HEMORR2HAGES) performed moderately well. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Expert opinion paper on atrial fibrillation detection after ischemic stroke.

PubMed

Haeusler, Karl Georg; Gröschel, Klaus; Köhrmann, Martin; Anker, Stefan D; Brachmann, Johannes; Böhm, Michael; Diener, Hans-Christoph; Doehner, Wolfram; Endres, Matthias; Gerloff, Christian; Huttner, Hagen B; Kaps, Manfred; Kirchhof, Paulus; Nabavi, Darius Günther; Nolte, Christian H; Pfeilschifter, Waltraud; Pieske, Burkert; Poli, Sven; Schäbitz, Wolf Rüdiger; Thomalla, Götz; Veltkamp, Roland; Steiner, Thorsten; Laufs, Ulrich; Röther, Joachim; Wachter, Rolf; Schnabel, Renate

2018-04-27

This expert opinion paper on atrial fibrillation detection after ischemic stroke includes a statement of the "Heart and Brain" consortium of the German Cardiac Society and the German Stroke Society. This paper was endorsed by the Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork. In patients with ischemic stroke, detection of atrial fibrillation should usually lead to a change in secondary stroke prevention, since oral anticoagulation is superior to antiplatelet drugs. The detection of previously undiagnosed atrial fibrillation can be improved in patients with ischemic stroke to optimize stroke prevention. This paper summarizes the present knowledge on atrial fibrillation detection after ischemic stroke. We propose an interdisciplinary standard for a "structured analysis of ECG monitoring" on the stroke unit as well as a staged diagnostic scheme for the detection of atrial fibrillation. Since the optimal duration and mode of ECG monitoring has not yet been finally established, this paper is intended to give advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on the expert opinion, reported case series and clinical experience. Therefore, this paper is not intended as a guideline.

Management of atrial fibrillation in Greece: the MANAGE-AF study.

PubMed

Andrikopoulos, George; Pastromas, Sokratis; Mantas, Ioannis; Sakellariou, Dimitris; Kyrpizidis, Christos; Makridis, Pantelis; Goumas, Georgios; Stakos, Dimitris; Gotsis, Alexandros; Kartalis, Athanasios; Kazianis, Georgios; Babalis, Dimitrios; Toli, Konstantina; Tzeis, Stylianos; Papavasileiou, Maria; Kalogeropoulos, Petros; Vardas, Panos

2014-01-01

Although atrial fibrillation (AF) is a highly prevalent health problem with high morbidity and mortality, data regarding the clinical characteristics and management of AF in the Greek population are scarce. The "Current Clinical Practice in the MANAGEment of Atrial Fibrillation in Greece" study (MANAGEAF) aimed to assess the epidemiological features as well as the daily clinical practice in the management of Greek patients with AF. Taking into consideration the distribution of the Greek population, 603 consecutive patients over 18 years of age, with any type of AF, presenting at the emergency departments or outpatient clinics of 27 different centers, were included in our study. The mean age of the patients was 68.5 ± 12.1 years, with male patients representing 52.5% of the study population. The most common AF type in our cohort was non-paroxysmal AF (60%), including the patients with permanent (24.1%), persistent (17.4%), long-standing (4.8%) and first diagnosed AF (13.8%). Hypertension was the most common comorbidity (70.3%). A history of stroke or transient ischemic attack was detected in 9.2% of the patients, while 6.2% had a history of gastrointestinal bleeding. About half of the patients (49.3%) were treated with anticoagulant drugs, mainly vitamin K antagonists (46.9%), while 34.2% were on antiplatelet drugs, aspirin and/or clopidogrel. The mean INR level (1.7 ± 0.8) was sub-therapeutic, although the mean values for CHADS2 and CHA2DS2-VASc scores were 1.6 ± 1.2 and 3.0 ± 1.7, respectively. The MANAGE-AF baseline results indicate unsatisfactory levels of compliance with the current guidelines for the management of AF in Greece. Considering the undisputed effectiveness of anticoagulant treatment for preventing AF-related strokes, MANAGE-AF demonstrates the need for optimization of our therapeutic strategies for the management of cardioembolic stroke risk.

[Update on the control of patients on treatment with vitaminK antagonist oral anticoagulants in Primary Care].

PubMed

Fernández López, P; López Ramiro, M I; Merino de Haro, I; Cedeño Manzano, G; Díaz Siles, F J; Hermoso Sabio, A

In Spain, more than 80% of patients with atrial fibrillation (AF) receive oral anticoagulant therapy (OAT), and 72% of these patients are followed up in the Primary Care (PC) setting. Recent studies have shown that there is insufficient control of patients on OAT. The objective of the present study was to obtain more detailed information on the state of control of patients on treatment with vitaminK antagonist (VKA) oral anticoagulants (OAC), on the diseases for which the therapy was indicated and on concomitant diseases. This was a retrospective, cross-sectional, observational study with the participation of patients from a single health area included in an OAT programme throughout 2014. In patients on treatment with OAC, International Normalised Ratio (INR) control was considered insufficient when the percentage time in therapeutic range (TTR) was below 65% during an evaluation period of at least 6months. A total of 368 patients were included in the study, where the most frequent indication for oral anticoagulation was non-valvular AF. A total of 5,128 INR controls were performed, of which 2,359 (46%) were outside the therapeutic range, and 2,769 (54%) were within range. The risk of thromboembolism was very high in 91% of patients on treatment with VKA OAC. The indication for anticoagulation is correct in our population, assuming a low-intermediate risk of haemorrhage in the majority of patients. Measurement of the TTR using the Rosendaal method shows that the control of patients on treatment with VKA OAC is insufficient. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Rivaroxaban real-world evidence: Validating safety and effectiveness in clinical practice.

PubMed

Beyer-Westendorf, Jan; Camm, A John; Coleman, Craig I; Tamayo, Sally

2016-09-28

Randomised controlled trials (RCTs) are considered the gold standard of clinical research as they use rigorous methodologies, detailed protocols, pre-specified statistical analyses and well-defined patient cohorts. However, RCTs do not take into account the complexity of real-world clinical decision-making. To tackle this, real-world data are being increasingly used to evaluate the long-term safety and effectiveness of a given therapy in routine clinical practice and in patients who may not be represented in RCTs, addressing key clinical questions that may remain. Real-world evidence plays a substantial role in supporting the use of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in clinical practice. By providing data on patient profiles and the use of anticoagulation therapies in routine clinical practice, real-world evidence expands the current awareness of NOACs, helping to ensure that clinicians are well-informed on their use to implement patient-tailored clinical decisions. There are various issues with current anticoagulation strategies, including under- or overtreatment and frequent monitoring with VKAs. Real-world studies have demonstrated that NOAC use is increasing (Dresden NOAC registry and Global Anticoagulant Registry in the FIELD-AF [GARFIELD-AF]), as well as reaffirming the safety and effectiveness of rivaroxaban previously observed in RCTs (XArelto on preveNtion of sTroke and non-central nervoUS system systemic embolism in patients with non-valvular atrial fibrillation [XANTUS] and IMS Disease Analyzer). This article will describe the latest updates in real-world evidence across a variety of methodologies, such as non-interventional studies (NIS), registries and database analyses studies. It is anticipated that these studies will provide valuable clinical insights into the management of thromboembolism, and enhance the current knowledge on anticoagulant use and outcomes for patients.

[Control of anticoagulation in patients with non-valvular atrial fibrillation in a primary care clinical practice setting in the different autonomous communities. PAULA study].

PubMed

Polo García, J; Barrios Alonso, V; Escobar Cervantes, C; Prieto Valiente, L; Lobos Bejarano, J M; Vargas Ortega, D; Prieto Díaz, M Á; Alonso Moreno, F J; Barquilla García, A

2017-04-01

To determine the differences between regions in the level of control of patients with non-valvular atrial fibrillation treated with vitamin K antagonists, included in the PAULA study. Observational, and coss-sectional/retrospective study, including 139 Primary Care physicians from 99 Health Care centres in all autonomous communities (except La Rioja). Anticoagulation control was defined as the time in therapeutic range assessed by either the direct method (poor control <60%), or the Rosendaal method (poor control <65%). A total of 1,524 patients were included. Small differences in baseline characteristics of the patients were observed. Differences in the percentage of time in therapeutic range were observed, according to the Rosendaal method (mean 69.0±17.7%), from 78.1%±16.6 (Basque Country) to 61.5±14% (Balearic Islands), by the direct method (mean 63.2±17.9%) from 73.6%±16.6 (Basque Country) to 57.5±15.7% (Extremadura). When comparing regions, in those where the Primary Care physicians assumed full control without restrictions on prescription, the percentage of time in therapeutic range by the direct method was 63.89 vs. 60.95% in those with restrictions (p=.006), by Rosendaal method, 69.39% compared with 67.68% (p=.1036). There are significant differences in the level of control between some regions are still inadequate. Regions in which the Primary Care physicians assumed the management of anticoagulation and without restrictions, time in therapeutic range was somewhat higher, and showed a favourable trend for better control. These findings may have clinical implications, and deserve consideration and specific analysis. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

[Clinical characteristics of patients with atrial fibrillation treated with direct oral anticoagulants attended in primary care setting. The SILVER-AP study].

PubMed

de la Figuera, Mariano; Cinza, Sergio; Marín, Nuria; Egocheaga, Isabel; Prieto, Miguel Angel

To analyse the clinical characteristics and management of patients with non-valvular atrial fibrillation (NVAF) treated with direct oral anticoagulants (DOAC). Observational, cross-sectional and multicentre study. Autonomous Communities in which the general practitioner can prescribe DOAC (n=9). The study included a total of 790 patients on chronic treatment with anticoagulants, and on whom therapy was changed, as well as being currently on treatment with DOAC for at least for 3 months. A record was made of the sociodemographic and clinical management date. Mean age was 78.6±8.4 years, and 50.5% of patients were men. Mean CHADS 2 score was 2.6±1.2, mean CHA 2 DS 2 -VASc score was 4.3±1.6, and the mean HAS-BLED score was 2.3±1.0. Mean duration of treatment with DOAC was 15.8±12.5 months. Rivaroxaban was the DOAC most frequently prescribed (57.8%), followed by dabigatran (23.7%), and apixaban (18.5%). Of the patients receiving rivaroxaban, 70.2% were taking the dose of 20mg/daily. Of the patients receiving dabigatran, 41.7% were taking the dose of 150mg twice daily, and in the case of apixaban, 56.2% were taking the dose of 5mg twice daily. Satisfaction (ACTS Burdens scale 52.0±7.2 and ACTS Benefits scale 12.1±2.2), and therapeutic adherence (97.8% of patients took their medication regularly) with DOAC were high. Patients treated with DOAC in Spain have a high thromboembolic risk. A significant proportion of patients receive a lower dose of DOAC than that recommended according to their clinical profile. Satisfaction and medication adherence are high. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Dual Antithrombotic Therapy with Clopidogrel and Novel Oral Anticoagulants in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Real-world Study.

PubMed

Kebernik, Julia; Borlich, Martin; Tölg, Ralph; El-Mawardy, Mohamed; Abdel-Wahab, Mohamed; Richardt, Gert

2018-06-01

For patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), proper antithrombotic therapy is equivocal. Current guidelines recommend triple therapy, which carries a high risk of bleeding. Recent large trials suggest that dual therapy (DT) with novel oral anticoagulant (NOAC) plus P2Y 12 inhibitor can be an appropriate alternative, but real-world data for this alternative are scarce and the optimal duration of DT has not yet been established. This analysis was performed in a single-center prospective cohort. We investigated 216 PCI patients with indication for anticoagulation due to AF. After PCI patients received DT with reduced doses NOAC plus P2Y 12 inhibitor for 6 months, which was followed by standard dose NOAC monotherapy. Efficacy endpoints were defined as cardiac death, myocardial infarction (MI), stent thrombosis (ST), and stroke. Safety endpoints were bleeding events as defined by Bleeding Academic Consortium (BARC). Baseline characteristics of our study population were described by a CHA 2 DS 2 -VASc score of greater than 4 and a HAS-BLED score of greater than 3. After a mean follow-up of 18.7 months, efficacy events occurred in 12 patients (5.6%). We observed three (1.4%) cardiac deaths, two (0.9%) MIs, six (2.8%) strokes, and one (0.5%) definite ST. After switching from DT to NOAC monotherapy after 6.3 ± 1.7 months, there was no rebound of ischemic events. Bleeding events occurred in 34 patients (15.7%) mainly under DT, while bleeding was less during NOAC monotherapy. In this long-term study of high-risk and real-world AF-patients with PCI, DT with NOAC and P2Y 12 inhibitor (6 months) followed by NOAC monotherapy was safe and effective.

Effectiveness, safety and costs of thromboembolic prevention in patients with non-valvular atrial fibrillation: phase I ESC-FA protocol study and baseline characteristics of a cohort from a primary care electronic database

PubMed Central

Vedia Urgell, Cristina; Roso-Llorach, Albert; Morros, Rosa; Capellà, Dolors; Castells, Xavier; Ferreira-González, Ignacio; Troncoso Mariño, Amelia; Diògene, Eduard; Elorza, Josep Mª; Casajuana, Marc; Bolíbar, Bonaventura; Violan, Concepció

2016-01-01

Purpose Atrial fibrillation is the most common arrhythmia. Its management aims to reduce symptoms and to prevent complications through rate and rhythm control, management of concomitant cardiac diseases and prevention of related complications, mainly stroke. The main objective of Effectiveness, Safety and Costs in Atrial Fibrillation (ESC-FA) study is to analyse the drugs used for the management of the disease in real-use conditions, particularly the antithrombotic agents for stroke prevention. The aim of this work is to present the study protocol of phase I of the ESC-FA study and the baseline characteristics of newly diagnosed patients with atrial fibrillation in Catalonia, Spain. Participants The data source is System for the Improvement of Research in Primary Care (SIDIAP) database. The population included are all patients with non-valvular atrial fibrillation diagnosis registered in the electronic health records during 2007–2012. Findings to date A total of 22 585 patients with non-valvular atrial fibrillation were included in the baseline description. Their mean age was 72.8 years and 51.6% were men. The most commonly prescribed antithrombotics were vitamin K antagonists (40.1% of patients) and platelet aggregation inhibitors (32.9%); 25.3% had not been prescribed antithrombotic treatment. Age, gender, comorbidities and co-medication at baseline were similar to those reported for previous studies. Future plans The next phase in the ESC-FA study will involve assessing the effectiveness and safety of antithrombotic treatments, analysing stroke events and bleeding episodes’ rates in our patients (rest of phase I), describing the current management of the disease and its costs in our setting, and assessing how the introduction of new oral anticoagulants changes the stroke prevention in non-valvular atrial fibrillation. PMID:26823179

Sustained impact of anticoagulant control achieved in an anticoagulation management service after transfer of management to the primary care physician.

PubMed

Bungard, Tammy J; Ritchie, Bruce; Garg, Sipi; Tsuyuki, Ross T

2012-02-01

To determine whether the impact of anticoagulant control achieved in an Anticoagulation Management Service (AMS) is sustained after transfer of anticoagulation management to the primary care physician (PCP), and to assess patient satisfaction with their anticoagulation management by both the AMS and PCP. Prospective, randomized trial. Pharmacist-directed ambulatory AMS located in a tertiary medical care facility and PCP practices in Canada. Sixty-two adults who had received at least 6 months of warfarin therapy managed by the AMS. Patients were randomly assigned to remain with AMS care (32 patients) or to transfer their anticoagulation management care to their PCP (30 patients). After 4.5 months of care, patients in both groups completed a validated survey instrument assessing their satisfaction with the management of their warfarin therapy. Of 295 patients screened, most were excluded from the study for denying consent or for having previous bleeding or clotting complications while taking warfarin. Patients in the AMS and PCP groups who completed the study were similar in age (median 70 and 76 yrs, respectively), and most had atrial fibrillation as an indication for warfarin (75% and 83%, respectively). The primary outcome measure-mean percentage of time within the desired international normalized ratio (INR) range after 6 months-was compared between the two groups, using both the actual range (INR 2.5 ± 0.5) and an expanded range (INR 2.5 ± 0.7). No significant difference was noted in this outcome between the groups (73.5 ± 19.1% vs 76.9 ± 24.5% for the AMS vs PCP groups, p=0.54). Other outcome measures were rates of thrombotic and hemorrhagic events resulting in emergency department visits or hospitalizations, patients' overall satisfaction with warfarin therapy, and patients' preferred anticoagulation management strategy. Two hemorrhagic events and one thrombotic event occurred in each group. Patients were more satisfied with their anticoagulant management by the AMS relative to PCP care (p=0.01), and given the choice, patients preferred AMS care (p=0.001). During this 6-month trial, anticoagulation control did not significantly differ between patients who continued to receive anticoagulation management by the AMS and those who transferred to their PCP for anticoagulation management, indicating that the effects of AMS care were sustained. Although patients were more satisfied and preferred to stay with AMS care, this study shows that select patients could have their anticoagulation care transferred to their PCP without compromising anticoagulation control. © 2012 Pharmacotherapy Publications, Inc.

Impact of Proteinuria and Glomerular Filtration Rate on Risk of Thromboembolism in Atrial Fibrillation: the ATRIA Study

PubMed Central

Go, Alan S.; Fang, Margaret C.; Udaltsova, Natalia; Chang, Yuchiao; Pomernacki, Niela K.; Borowsky, Leila; Singer, Daniel E.

2009-01-01

Background Atrial fibrillation (AF) substantially increases the risk of ischemic stroke but this risk varies among individual patients with AF. Existing risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for ischemic stroke in persons with AF is unknown. Methods and Results We examined how chronic kidney disease (reduced glomerular filtration rate or proteinuria) affects risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Patient characteristics, warfarin use, and thromboembolic events were ascertained from clinical databases, with validation of thromboembolism by chart review. Results During 33,165 person-years off anticoagulation among 10,908 patients with atrial fibrillation, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and other confounders, proteinuria increased the risk of thromboembolism by 54% (relative risk [RR] 1.54, 1.29 to 1.85) and there was a graded, increased risk of stroke associated with progressively lower level of eGFR compared with eGFR ≥60 (in units of ml/min/1.73 m2): RR 1.16 (95% CI: 0.95−1.40) for eGFR 45−59 and RR 1.39 (95% CI: 1.13−1.71) for eGFR <45 (P=0.0082 for trend). Conclusions . Chronic kidney disease increases the risk of thromboembolism in AF independent of other risk factors. Knowing the level of kidney function and presence of proteinuria may improve risk stratification for decision-making about the use of antithrombotic therapy for stroke prevention in AF. PMID:19255343

Combining value of information analysis and ethical argumentation in decisions on participation of vulnerable patients in clinical research.

PubMed

van der Wilt, Gert J; Grutters, Janneke P C; Maas, Angela H E M; Rolden, Herbert J A

2018-02-05

The participation of vulnerable patients in clinical research poses apparent ethical dilemmas. Depending on the nature of the vulnerability, their participation may challenge the ethical principles of autonomy, non-maleficence, or justice. On the other hand, non-participation may preclude the building of a knowledge base that is a prerequisite for defining the optimal clinical management of vulnerable patients. Such clinical uncertainty may also incur substantial economic costs. We present the participation of pre-menopausal women with atrial fibrillation in trials of novel oral anticoagulant drugs as a case study. Due to their non-participation in pivotal trials, it is uncertain whether for them, the risks that are associated with these drugs are outweighed by the advantages compared with conventional treatment. We addressed the question whether research of this new class of drugs in this subgroup would be appropriate from both, an ethical as well an economic perspective. We used the method of specifying norms as a wider framework to resolve the apparent ethical dilemma, while incorporating the question whether research of oral anticoagulants in premenopausal women with atrial fibrillation can be justified on economic grounds. For the latter, the results of a value-of-information analysis were used. Further clinical research on NOACs in premenopausal women with atrial fibrillation can be justified on both, ethical and economic grounds. Addressing apparent ethical dilemmas by invoking a method such as specifying norms can improve the quality of public practical reasoning. As such, the method should also prove valuable to committees that have formally been granted the authority to review trial protocols and proposals for scientific research.

Risk of atrial fibrillation in diabetes mellitus: A nationwide cohort study.

PubMed

Pallisgaard, Jannik L; Schjerning, Anne-Marie; Lindhardt, Tommi B; Procida, Kristina; Hansen, Morten L; Torp-Pedersen, Christian; Gislason, Gunnar H

2016-04-01

Diabetes has been associated with atrial fibrillation but the current evidence is conflicting. In particular knowledge regarding young diabetes patients and the risk of developing atrial fibrillation is sparse. The aim of our study was to investigate the risk of atrial fibrillation in patients with diabetes compared to the background population in Denmark. Through Danish nationwide registries we included persons above 18 years of age and without prior atrial fibrillation and/or diabetes from 1996 to 2012. The study cohort was divided into a background population without diabetes and a diabetes group. The absolute risk of developing atrial fibrillation was calculated and Poisson regression models adjusted for sex, age and comorbidities were used to calculate incidence rate ratios of atrial fibrillation. The total study cohort included 5,081,087 persons, 4,827,713 (95%) in the background population and 253,374 (5%) in the diabetes group. Incidence rates of atrial fibrillation per 1000 person years were stratified in four age groups from 18 to 39, 40 to 64, 65 to 74 and 75 to 100 years giving incidence rates (95% confidence intervals) of 0.02 (0.02-0.02), 0.99 (0.98-1.01), 8.89 (8.81-8.98) and 20.0 (19.9-20.2) in the background population and 0.13 (0.09-0.20), 2.10 (2.00-2.20), 8.41 (8.10-8.74) and 20.1 (19.4-20.8) in the diabetes group, respectively. The adjusted incidence rate ratios in the diabetes group with the background population as reference were 2.34 (1.52-3.60), 1.52 (1.47-1.56), 1.20 (1.18-1.23) and 0.99 (0.97-1.01) in the four age groups, respectively. Diabetes is an independent risk factor for developing atrial fibrillation/flutter, most pronounced in young diabetes patients. Routine screening for atrial fibrillation/flutter in diabetes patients might be beneficial and have therapeutic implications, especially in younger diabetes patients. Diabetes increases the risk of developing atrial fibrillation and especially young diabetes patients have a high relative risk. Increased focus on detecting atrial fibrillation in young diabetes patients might prove beneficial, and both anticoagulation treatment and anti-arrhythmic treatment strategies should be considered as soon as possible. © The European Society of Cardiology 2015.

Cerebral amyloid angiopathy, cerebral microbleeds and implications for anticoagulation decisions: The need for a balanced approach.

PubMed

Charidimou, Andreas; Shoamanesh, Ashkan; Al-Shahi Salman, Rustam; Cordonnier, Charlotte; Perry, Luke A; Sheth, Kevin N; Biffi, Alessandro; Rosand, Jonathan; Viswanathan, Anand

2018-02-01

Cerebral amyloid angiopathy is a common hemorrhagic small vessel disease of the brain, often associated with high risk of spontaneous lobar intracerebral hemorrhage. When the suspicion of cerebral amyloid angiopathy is raised, clinicians are hesitant in prescribing oral anticoagulation in patients in whom it is otherwise indicated, including the case of non-valvular atrial fibrillation. This is one of the thorniest clinical dilemmas in the field currently. In this short Leading Opinion piece by an international panel of clinicians-researchers active in the field, we present our consistent approach and future outlook on oral anticoagulation post intracerebral hemorrhage and in the setting of clinical-radiologic evidence of cerebral amyloid angiopathy. We discuss recent advances and support a more balanced approach with implications for the wider neurological clinical community in regards to successful recruiting this patient population in ongoing and future randomized trials.

Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options—a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference

PubMed Central

Kirchhof, Paulus; Lip, Gregory Y.H.; Van Gelder, Isabelle C.; Bax, Jeroen; Hylek, Elaine; Kaab, Stefan; Schotten, Ulrich; Wegscheider, Karl; Boriani, Giuseppe; Brandes, Axel; Ezekowitz, Michael; Diener, Hans; Haegeli, Laurent; Heidbuchel, Hein; Lane, Deirdre; Mont, Luis; Willems, Stephan; Dorian, Paul; Aunes-Jansson, Maria; Blomstrom-Lundqvist, Carina; Borentain, Maria; Breitenstein, Stefanie; Brueckmann, Martina; Cater, Nilo; Clemens, Andreas; Dobrev, Dobromir; Dubner, Sergio; Edvardsson, Nils G.; Friberg, Leif; Goette, Andreas; Gulizia, Michele; Hatala, Robert; Horwood, Jenny; Szumowski, Lukas; Kappenberger, Lukas; Kautzner, Josef; Leute, Angelika; Lobban, Trudie; Meyer, Ralf; Millerhagen, Jay; Morgan, John; Muenzel, Felix; Nabauer, Michael; Baertels, Christoph; Oeff, Michael; Paar, Dieter; Polifka, Juergen; Ravens, Ursula; Rosin, Ludger; Stegink, W.; Steinbeck, Gerhard; Vardas, Panos; Vincent, Alphons; Walter, Maureen; Breithardt, Günter; Camm, A. John

2012-01-01

While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. PMID:21791573

Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation.

PubMed

Camm, A John; Pinto, Fausto J; Hankey, Graeme J; Andreotti, Felicita; Hobbs, F D Richard

2015-07-01

Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Dabigatran etexilate versus warfarin as the oral anticoagulant of choice? A review of clinical data.

PubMed

Ma, Terry K W; Yan, Bryan P; Lam, Yat-Yin

2011-02-01

For many years, warfarin was the only effective oral anticoagulant to prevent and treat thromboembolism. Nevertheless, its clinical use is limited by a narrow therapeutic window, extensive drug interactions, need of strict dietary control and frequent monitoring. The pharmacological response is also unpredictable and highly variable among patients. Suboptimal anticoagulation can lead to detrimental thromboembolic events or life-threatening bleeding. Direct thrombin inhibitor (DTI) activity represents a new class of anticoagulant activity that was intended to replace warfarin. Ximelagatran was the first DTI shown to have similar efficacy to warfarin, but failed to replace it because of a high incidence of liver toxicity. Dabigatran etexilate is another novel DTI with a more predictable pharmacokinetic profile and fewer drug interactions compared with warfarin. Recent large-scaled, randomized studies have shown that it does not share ximelagatran's hepatotoxicity, and is as effective as conventional anticoagulants for venous thromboembolism (VTE) and prophylaxis in atrial fibrillation (AF). These findings led to the approval of dabigatran etexilate for thromboprophylaxis following hip or knee replacement surgery in Europe, Canada and the United Kingdom. Here we summarize the latest evidence concerning the use of dabigatran etexilate in VTE (BISTRO, RE-MODEL, RE-NOVATE, RE-MOBILIZE and RECOVER) and AF (PETRO and RELY). Potential problems related to dabigatran use are also discussed to examine whether it can truly replace warfarin as the gold standard. Copyright © 2010 Elsevier Inc. All rights reserved.

Modelling the cost-effectiveness of pharmacist-managed anticoagulation service for older adults with atrial fibrillation in Singapore.

PubMed

Chua, Wen Bing Brandon; Cheen, Hua Heng McVin; Kong, Ming Chai; Chen, Li Li; Wee, Hwee Lin

2016-10-01

Background Oral anticoagulation with warfarin is the cornerstone therapy in atrial fibrillation (AF) for stroke prevention. Multi-disciplinary anticoagulation management services have been shown to be cost-effective in the United States, Hong Kong and Thailand, but the findings are not readily generalizable to Singapore's healthcare system. Objective This study aimed to evaluate the cost-effectiveness of pharmacist-managed anticoagulation clinic (ACC) compared with usual care (UC) for the management of older adults with AF receiving oral anticoagulation with warfarin. Setting Pharmacist-managed ACC in an academic medical centre. Method A Markov model with 3-month cycle length and 30-year time horizon compared costs and quality-adjusted life-years (QALYs) of ACC and UC from the patient's and healthcare provider's perspectives. Four pathways based on time in therapeutic range (TTR) were: ACC TTR < 70 %, ACC TTR ≥ 70 %, UC TTR < 70 % and UC TTR ≥ 70 %. A hypothetical cohort of 70-year-old Singaporean AF patients receiving warfarin was utilised. Local data from national disease registries, patient surveys and hospital databases were used. When local data was not available, published studies on Asian populations were utilized when available. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to account for uncertainties. Costs and QALYs were discounted annually by 3 %. Main outcome measure Costs and QALYs of ACC and UC. Results Pharmacist-managed ACC was found to dominate UC in all comparisons. It improved effectiveness by 0.19 and 0.13 QALYs at TTR < 70 % and TTR ≥ 70 % respectively compared with UC. From the patient's perspective, ACC reduced costs by SG$1222.67 (€1110.24) for TTR < 70 % and SG$1008.16 (€915.46) for TTR ≥ 70 %. Similar trends were observed from the healthcare provider's perspective, with ACC reducing costs by SG$1444.79 (€1311.94) for TTR < 70 % and SG$1269.17 (€1152.46) for TTR ≥ 70 % compared with UC. The results were robust to variations of the parameters over their plausible ranges in one-way sensitivity analyses. Probabilistic sensitivity analyses demonstrated that ACC was cost-effective more than 79 % of the time from both perspectives at a willingness-to-pay threshold of SG$69,050 (€62,701) per QALY. Conclusion Pharmacist-managed ACC is more effective and less costly compared with UC regardless of the quality of anticoagulation therapy. The findings support the current body of evidence demonstrating the cost-effectiveness of ACC.

Spontaneous conversion of atrial fibrillation caused by severe hyperkalemia: A case report.

PubMed

Yan, Lihua; Jiang, Tingbo; Yang, Xiangjun; Xu, Mingzhu

2018-04-01

Hyperkalemia is a life-threatening electrolyte disturbance which could lead to arrhythmias and potentially death. An 82-year-old male patient who presented typical electrocardiographic indications of hyperkalemia, including the absence of P waves, prolongation of QRS complex, sinoventricular conduction, bradyarrhythmia and tall peaked T waves. He developed a rare self-defibrillation of atrial fibrillation to sinus rhythm due to hyperkalemia. Besides, he developed secondary thrombosis caused by abrupt termination of atrial fibrillation. This patient was diagnosed with hyperkalemia, hypertension, and AF. He was treated with an intravenous infusion of calcium gluconate, insulin and dextrose, an oral kayexalate, and emergency hemodialysis. The patient was managed effectively and discharged with stable status. Hyperkalemia could induce malignant arrhythmia with high mortality. Thus we suggested more attention be paid to monitoring electrolyte disorders and maintaining anticoagulation treatments to avoid thromboembolism.

Atrial Fibrillation: Epidemiology and Peculiarities in the Elderly.

PubMed

da Silva, Rose Mary Ferreira Lisboa

2015-01-01

The prevalence of atrial fibrillation (AF) increases with age and two-thirds of patients with AF aged over 75 years. In addition, comorbidities are frequent in the elderly and worsen the prognosis. There are poorer quality of life, increased number of hospitalizations and cardiovascular events. The annual death rate was 8% in patients older than 75 years, and higher among women. There is a significant association between AF and cognitive disorders. Despite highest stroke risk, elderly have been paradoxically less likely to receive oral anticoagulation. This review summarizes available data on the epidemiology, risk factors, and scores of bleeding and systemic embolism, evolution and the approach of elderly patients with AF.

[Comparison of quality and hemorragic risk of oral anticoagulant therapy using acenocoumarol versus warfarin].

PubMed

Oliva Berini, Elvira; Galán Alvarez, Pilar; Pacheco Onrubia, Ana María

2008-06-21

Long half life oral anticoagulants have shown a higher anticoagulation stability and a lower hemorragic risk than those of a short half life. We have compared therapeutic stability and hemorragic risk of acenocoumarol versus warfarin in 2 groups of patients on preventive anticoagulation because of atrial fibrilation (international normalised ratio [INR]: 2-3). Data on 120 patients treated with acenocoumarol and 120 on warfarin treatment who had started and continued treatment in our hospital for a minimum of a year was collected. The percentage of visits within the intended range of INR (2 to 3) was 65.5% with warfarin and 63.4% with acenocoumarol. Thirty percent of patients on warfarin had 75% or more of their controls within range, while for those treated with acenocoumarol this percentage was 22.5%. In the acenocoumarol group, 0.3 visits/patient/year presented an INR > or = 6 versus 0.07 in the warfarin group (p = 0.003). Patients treated with acenocoumarol show a higher risk of presenting with an INR > or = 6, but no statistically significant differences are observed in therapeutic stability.

Switching, Adverse Effects and Use of Over-the-Counter Analgesics among Users of Oral Anticoagulants: A Pharmacy-based Survey.

PubMed

Hellfritzsch, Maja; Hyllested, Lea Maria Rønneberg; Meegaard, Line; Wiberg-Hansen, Alexander; Grove, Erik Lerkevang; Pottegård, Anton

2017-07-01

Oral anticoagulants are widely used but information on important aspects in that respect is not available from medical registers or clinical databases. Therefore, we conducted a survey including patients filling a prescription for oral anticoagulants at two large Danish community pharmacies. We collected information concerning the patients' knowledge of their anticoagulant treatment including prior drug switching. Further, patients were asked about use of over-the-counter analgesics, adverse effects and how the treatment affected their everyday life. Among 335 eligible patients, 301 (90%) agreed to participate. Atrial fibrillation was the most common indication (65%), and most patients filled a prescription for a non-vitamin K antagonist oral anticoagulant (NOAC) (58%). Among the 12% (n = 35) of participants who had switched oral anticoagulant treatment, 69% had switched from a vitamin K antagonist (VKA) to a NOAC. Switching was most frequently caused by inconvenience (34%) and adverse effects (23%). Although half of all patients had recently bought over-the-counter analgesics, purchase of ibuprofen and aspirin was rare (6%). More VKA users than NOAC users felt limited in their everyday life because of anticoagulant treatment (18% versus 9%). Among non-incident NOAC users, 21% had experienced adverse effects during their current treatment. Based on first-hand information from a large sample of anticoagulant users, we conclude that the main drug-related issues leading to anticoagulant switching and perceived limitations in everyday life were inconvenience and adverse effects. This varied between drug groups. Further, use of NSAIDs obtained over the counter was rare. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Oral anticoagulant use in cardiovascular disorders: a perspective on present and potential indications for rivaroxaban.

PubMed

Camm, A John; Fox, Keith A A

2018-05-21

Four non-vitamin-K-antagonist oral anticoagulants (NOACs) have been approved for use in various cardiovascular indications. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban are now increasingly used in clinical practice. For some of these agents, available data from real-world studies support the efficacy and safety data in phase III clinical trials. This review aims to summarize the current status of trials and observational studies of oral anticoagulant use over the spectrum of cardiovascular disorders (excluding venous thrombosis), provide a reference source beyond stroke prevention for atrial fibrillation (AF) and examine the potential for novel applications in the cardiovascular field. We searched the recent literature for data on completed and upcoming trials of oral anticoagulants with a particular focus on rivaroxaban. Recent data in specific patient subgroups, such as patients with AF undergoing catheter ablation or cardioversion, have led to an extended approval for rivaroxaban, whereas the other NOACs have ongoing or recently completed trials in this setting. However, there are unmet medical needs for several arterial thromboembolic-related conditions, including patients with: AF and acute coronary syndrome, AF and coronary artery disease undergoing elective percutaneous coronary intervention, coronary artery disease and peripheral artery disease, implanted cardiac devices, and embolic stroke of unknown source. NOACs may provide alternative treatment options in areas of unmet need, and numerous studies are underway to assess their benefit-risk profiles in these settings.

Atrial fibrillation and stroke: the evolving role of rhythm control.

PubMed

Patel, Taral K; Passman, Rod S

2013-06-01

Atrial fibrillation (AF) remains a major risk factor for stroke. Unfortunately, clinical trials have failed to demonstrate that a strategy of rhythm control--therapy to maintain normal sinus rhythm (NSR)--reduces stroke risk. The apparent lack of benefit of rhythm control likely reflects the difficulty in maintaining NSR using currently available therapies. However, there are signals from several trials that the presence of NSR is indeed beneficial and associated with better outcomes related to stroke and mortality. Most electrophysiologists feel that as rhythm control strategies continue to improve, the crucial link between rhythm control and stroke reduction will finally be demonstrated. Therefore, AF specialists tend to be aggressive in their attempts to maintain NSR, especially in patients who have symptomatic AF. A step-wise approach from antiarrhythmic drugs to catheter ablation to cardiac surgery is generally used. In select patients, catheter ablation or cardiac surgery may supersede antiarrhythmic drugs. The choice depends on the type of AF, concurrent heart disease, drug toxicity profiles, procedural risks, and patient preferences. Regardless of strategy, given the limited effectiveness of currently available rhythm control therapies, oral anticoagulation is still recommended for stroke prophylaxis in AF patients with other stroke risk factors. Major challenges in atrial fibrillation management include selecting patients most likely to benefit from rhythm control, choosing specific antiarrhythmic drugs or procedures to achieve rhythm control, long-term monitoring to gauge the efficacy of rhythm control, and determining which (if any) patients may safely discontinue anticoagulation if long-term NSR is achieved.

The anticoagulant effect of therapeutic levels of dabigatran in atrial fibrillation evaluated by thrombelastography (TEG®), Hemoclot Thrombin Inhibitor (HTI) assay and Ecarin Clotting Time (ECT).

PubMed

Solbeck, Sacha; Jensen, Annette Schophuus; Maschmann, Christian; Stensballe, Jakob; Ostrowski, Sisse Rye; Johansson, Pär I

Monitoring the effect of dabigatran (Pradaxa ® ) is challenging. The aim of this study was to evaluate if thrombelastography reaction time (TEG ® R) could detect the anticoagulant effect of dabigatran showing a correlation between TEG ® R, Hemoclot Thrombin Inhibitor (HTI) assay and Ecarin Clotting Time (ECT) in patients with non-valvular atrial fibrillation (NVAF). Blood samples from 35 AF patients receiving either 110 mg (n 19) or 150 mg (n 16) dabigatran twice daily were analyzed with TEG ® , HTI and ECT 2-3 h after dabigatran intake. All patients had prolonged TEG ® R. The patients receiving dabigatran 110 mg ×2 had a TEG ® R mean 14.2 min (range 9.1-25), a mean dabigatran concentration measured by HTI of 268.5 ng/mL (range 54-837 ng/mL) and by ECT of 355.7 ng/mL (range 40-1020 ng/mL). The corresponding numbers for patients receiving dabigatran 150 mg ×2 were TEG ® R mean of 12.5 min (range 9.2-23.2 min), mean dabigatran concentration of 179.2 ng/mL by HTI (range 26-687 ng/mL) and by ECT 225.1 ng/mL (range 42-1020 ng/mL). The two dosage groups had comparable anticoagulation demonstrated by equally prolonged TEG ® R (p = .909), HTI (p = .707) and ECT (p = .567). No difference in creatinine levels in the two dosage groups was observed (p = .204) though patients with dabigatran concentration >400 ng/mL had significantly higher creatinine levels (p = .001). Large individual variation of the anticoagulant response was observed. Some patients had TEG ® R values up to three times upper normal limit with immediate risk of bleeding. Our data indicate that TEG ® R reflected dabigatran levels in NVAF patients and that TEG ® R correlated to HTI and ECT.

Triple anticoagulation therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention – real life assessment

PubMed Central

Kabłak-Ziembicka, Anna; Bryniarski, Krzysztof; Wrotniak, Leszek; Ostrowska-Kaim, Elżbieta; Żmudka, Krzysztof; Przewłocki, Tadeusz

2016-01-01

Introduction Triple anticoagulation therapy (TT), comprising dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC), is essential in atrial fibrillation (AF) patients after percutaneous coronary intervention (PCI), but it increases the bleeding risk. Aim To assess TT models, in- and out-hospital bleeding and thromboembolic complications, and TT alterations. Material and methods During 12 months, consecutive AF post-PCI patients were scheduled for TT. Alterations in TT and thromboembolic events (death, myocardial infarction, ischemic stroke, in-stent thrombosis, peripheral embolization) were recorded. Major, non-major and minor bleeding episodes were assessed. Results One hundred and thirty-six out of 3171 patients, aged 73.0 ±8.4 years (90 male), were included. Intra-hospitally, thrombotic events occurred in 9 (6.6%), while bleeding events occurred in 71 (52.2%) patients. Access-site hematoma and blood transfusions during in-hospital stay predisposed physicians to heparin administration as part of TT on discharge (p = 0.018 and p = 0.033 respectively). Eventually, DAPT plus warfarin or plus novel oral anticoagulant (NOAC) or plus low molecular weight heparin was prescribed in 72 (52.9%), 53 (39%), and 11 (8.1%) patients, respectively. HAS-BLED and CHA2DS2-VASc scores were similar between subgroups (p = 0.63 and p = 0.64 respectively). During 10.2 ±4.2 months of follow-up, 11 (8.1%) deaths, and 9 (6.6%) non-fatal thromboembolic events occurred. Bleeding events occurred in 45 (34.6%) patients, including 14 (10.3%) major. TT was the only factor associated with increased risk of major bleeding (18.6% vs. 4.2%, p = 0.008). Early termination of any TT component, which concerned 59 (45.4%) patients, did not increase the risk of thromboembolic events (p = 0.89). Conclusions Our study indicates that TT is associated with high mortality and bleeding rates in a relatively short period of time. Discontinuation of any TT drug did not increase the thromboembolic event rate, while it was associated with reduced risk of major bleeding. PMID:27980543

The Translation of Knowledge into Practice in the Management of Atrial Fibrillation in Singapore.

PubMed

Woo, Fong Yeong Brigitte; Lim, Toon Wei; Tam, Wai San Wilson

2018-03-12

Atrial fibrillation (AF) is a clinically significant cardiac arrhythmia known to increase the risk of stroke by at least four times. Stroke-risk assessment and thromboprophylaxis are vital components in AF management. Guidelines are available to standardise AF management, but physicians' adherence to the recommended guidelines has been low. The aims were to: 1. Examine and compare the level of knowledge and current practice in AF management between cardiologists and non-cardiologist physicians in Singapore; 2. Identify physicians' perceived barriers to prescribing oral anticoagulants (OACs) when indicated; 3. Identify strategies to optimise AF management. From June 2017 to August 2017, a cross-sectional online survey involving physicians was conducted in Singapore. The survey instrument was adapted from a previously developed instrument, and validated locally by five cardiologists. It explored the physicians' stroke-risk assessment practices, estimation of stroke risk and benefits of anticoagulation, likelihood of prescribing anticoagulation when indicated, perceived barriers to anticoagulation, and strategies to optimise AF management. Sixty-three physicians completed the survey (14 cardiologists and 49 non-cardiologist physicians). No significant difference was found between cardiologists and non-cardiologist physicians in their assessment and estimation of stroke risk for stable AF patients. However, when presented with an AF patient with stroke risk, cardiologists were more likely than non-cardiologist physicians to prescribe novel OACs (93% vs. 51%; χ 2 =7.933, p=0.004). Compared to cardiologists, the majority of the non-cardiologist physicians thought the risk of falls were usually or always barriers to prescribing OACs (29% vs 69%; χ 2 =7.579, p=0.006). Among the suggested strategies to support them in AF management, physicians have overwhelmingly rated two as "quite useful" and "very useful": the establishment of clinics for monitoring anticoagulated patients (100%); and involvement of pharmacists in managing patients on warfarin (98.4%). Physicians possess good knowledge about stroke-risk assessment in AF patients yet it is not translated into effective measures for stroke prevention. Physicians, especially non-cardiologist ones, were not anticoagulating AF patients when indicated. Although novel OACs are safer alternatives to warfarin, non-cardiologist physicians were less inclined to use them for stroke prevention. All physicians opined that establishing anticoagulation clinics and collaborating with pharmacists were useful strategies to optimise AF management. Existing barriers to anticoagulation impeded the translation of knowledge into practice in the management of AF patients in Singapore, for which optimal strategies to optimise AF management are ascertained. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Acute management of stroke patients taking non-vitamin K antagonist oral anticoagulants Addressing Real-world Anticoagulant Management Issues in Stroke (ARAMIS) Registry: Design and rationale.

PubMed

Xian, Ying; Hernandez, Adrian F; Harding, Tina; Fonarow, Gregg C; Bhatt, Deepak L; Suter, Robert E; Khan, Yosef; Schwamm, Lee H; Peterson, Eric D

2016-12-01

Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients. The ARAMIS Registry is a multicenter cohort study of acute stroke patients who were taking chronic anticoagulation therapy prior to admission and are admitted with either an acute ischemic stroke or intracerebral hemorrhage. Built upon the existing infrastructure of American Heart Association/American Stroke Association Get With the Guidelines Stroke, the ARAMIS Registry will enroll a total of approximately 10,000 patients (5000 with acute ischemic stroke who are taking a NOAC and 5000 with anticoagulation-related intracerebral hemorrhage who are on warfarin or a NOAC). The primary goals of the ARAMIS Registry are to provide a comprehensive picture of current treatment patterns and outcomes of acute ischemic stroke patients on NOACs, as well as anticoagulation-related intracerebral hemorrhage in patients on either warfarin or NOACs. Beyond characterizing the index hospitalization, up to 2500 patients (1250 ischemic stroke and 1250 intracerebral hemorrhage) who survive to discharge will be enrolled in an optional follow-up sub-study and interviewed at 3 and 6 months after discharge to assess longitudinal medication use, downstream care, functional status, and patient-reported outcomes. The ARAMIS Registry will document the current state of management of NOAC treated patients with acute ischemic stroke as well as contemporary care and outcome of anticoagulation-related intracerebral hemorrhage. These data will be used to better understand optimal strategies to care for these complex but increasingly common emergent real world clinical challenges. Copyright © 2016 Elsevier Inc. All rights reserved.

Management of antithrombotic therapy in patients with coronary artery disease or atrial fibrillation who underwent abdominal surgical operations.

PubMed

Schizas, Dimitrios; Kariori, Maria; Boudoulas, Konstantinos Dean; Siasos, Gerasimos; Patelis, Nikolaos; Kalantzis, Charalampos; Carmen-Maria, Moldovan; Vavuranakis, Manolis

2018-04-02

Patients treated with antithrombotic therapy that require abdominal surgical procedures has progressively increased overtime. The management of antithrombotics during both the peri- and post- operative period is of crucial importance. The goal of this review is to present current data concerning the management of antiplatelets in patients with coronary artery disease and of anticoagulants in patients with atrial fibrillation who had to undergo abdominal surgical operations. For this purpose, incidence of major adverse cardiovascular events (MACE) and risk of antithrombotic use during surgical procedures, as well as the recommendations based on recent guidelines were reported. A thorough search of PubMed, Scopus and the Cochrane Databases was conducted to identify randomized controlled trials, observational studies, novel current reviews, and ESC and ACC/AHA guidelines on the subject. Antithrombotic use in daily clinical practice results to two different pathways: reduction of thromboembolic risk, but a simultaneous increase of bleeding risk. This may cause a therapeutic dilemma during the perioperative period. Nevertheless, careless cessation of antithrombotics can increase MACE and thromboembolic events, however, maintenance of antithrombotic therapy may increase bleeding complications. Studies and current guidelines can assist clinicians in making decisions for the treatment of patients that undergo abdominal surgical operations while on antithrombotic therapy. Aspirin should not be stopped perioperatively in the majority of surgical operations. Determining whether to discontinue the use of anticoagulants before surgery depends on the surgical procedure. In surgical operations with a low risk for bleeding, oral anticoagulants should not be discontinued. Bridging therapy should only be considered in patients with a high risk of thromboembolism. Finally, patients with an intermediate risk for thromboembolism, management should be individualized according to patient's thrombotic and bleeding risk. Management of antithrombotics therapy during the perioperative period in patients undergoing abdominal surgery should follow a patient-centered approach according to a patient's medical history and thrombotic risk weighted for bleeding risk. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Predicting Hemorrhagic Transformation of Acute Ischemic Stroke: Prospective Validation of the HeRS Score.

PubMed

Marsh, Elisabeth B; Llinas, Rafael H; Schneider, Andrea L C; Hillis, Argye E; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F

2016-01-01

Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort.A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis.Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P < 0.001), white blood cell count (P < 0.001), and warfarin use prior to admission (P = 0.002) were also associated with HT in the validation cohort. With these variables, AUC improved to 0.854. Anticoagulation did not significantly increase HT; but with higher intensity anticoagulation, hemorrhages were more likely to be symptomatic and more severe.The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation.

Severe mitral stenosis with atypical presentation: hemorrhagic pleural effusion--a case report and literature review.

PubMed

Albalbissi, Kais A; Burress, Jonathan W; Garcia, Israel D; Iskandar, Said B

2009-02-01

Mitral stenosis is a well-described valvular heart disease. We report a 68-year-old patient with an unusual presentation of mitral stenosis. He presented with recurrent episodes of hemorrhagic pleural effusion. Afterwards, an extensive atrial thrombosis complicated his course of illness. We will discuss how the clinical presentation of mitral stenosis is mainly dictated by the underlying pathophysiology of the disease. Also, the need for anticoagulation in the setting of mitral stenosis is often linked to the presence of atrial fibrillation. We will discuss the independent risk factors for thromboembolism in the setting of mitral stenosis. Finally, a review of the current recommendation for anticoagulation is conferred.

Evaluation of Bleeding Events Requiring Hospitalization in Patients With Atrial Fibrillation Receiving Dabigatran, Warfarin, or Antiplatelet Therapy.

PubMed

Riley, Tanya R; Gauthier-Lewis, Mary L; Sanchez, Chelsea K; Riley, Treavor T

2017-04-01

To determine the incidence and severity of bleeding events requiring hospitalization among patients with atrial fibrillation (AF) receiving anticoagulants (dabigatran or warfarin) or antiplatelet agents (eg, aspirin and clopidogrel). This was a single-center, retrospective cohort study involving 1494 patients with AF hospitalized from November 1, 2010, to November 1, 2011, with prior warfarin, dabigatran, or antiplatelet therapy. Overall bleeding events in the dabigatran group compared to the warfarin group were 24% and 12%, respectively ( P = .004). Of these events, individually, there were no significant differences in major (56% vs 58%, P = .88), life-threatening (25% vs 36%, P = .38), or minor bleeding (44% vs 42%, P = .06). Gastrointestinal (GI) bleeding occurred more in the dabigatran group compared to the warfarin group ( P = .02). Intracranial bleeding occurred in 15% of patients in the warfarin group and did not occur at all in the dabigatran group. Warfarin patients had significantly more overall bleeding events compared to antiplatelet therapy ( P < .001), with an increasing trend seen in major bleeding ( P = .06). GI bleeding, however, favored the warfarin group over the antiplatelet group (48% vs 73%, P = .04). Anticoagulation with dabigatran was associated with an overall increased occurrence of bleeding requiring hospital admission compared to warfarin. GI bleeding was more prevalent with dabigatran and antiplatelets than with warfarin. There were more intracranial hemorrhages seen in the warfarin group.

Survey of Antithrombotic Treatment in Rural Patients (>60 years) with Atrial Fibrillation in East China.

PubMed

Wei, Yong; Xu, Juan; Wu, Haiqing; Zhou, Genqing; Chen, Songwen; Wang, Caihong; Shen, Yahong; Yang, Shunhong; Wang, Bin; He, Zheng; Sun, Jianping; Sun, Weidong; Ouyang, Ping; Liu, Shaowen

2018-05-01

The prevalence and antithrombotic treatment of atrial fibrillation (AF) in Chinese rural population is not well known. The aim of this study was to investigate the extent to which antithrombotic treatment was prescribed for rural AF patients >60 years. We identified 828 AF patients from 36734 rural residents >60 years in Shanghai China. Our data indicated the overall prevalence rate of AF was 2.3% in rural population >60 years in East China and 38.9% of AF patients underwent antithrombotic therapy, including warfarin (5.9%), aspirin (29.6%), clopidogrel (2.9%) and aspirin combined with clopidogrel (0.5%). Of enrolled subjects, 98.4% had CHA 2 DS 2 -VASc score ≥1, 72.0% had HAS-BLED score <3 and 59.2% had CHA 2 DS 2 -VASc score ≥2 with HAS-BLED score <3. Missing early detection (34.9%), delay in seeking treatment for asymptomatic AF (25.5%) and doctors's incomplete inform of AF-related risk of stroke to patients (21.7%) were three dominant causes for failing anticoagulant usage. In conclusion, most AF patients were with a high risk of thrombosis and a low risk of bleeding in China, but a large majority of them failed to take anticoagulants mainly for missing an early screening of AF and lack of awareness on AF for both patients and primary care physicians.

Early initiation of new oral anticoagulants in acute stroke and TIA patients with nonvalvular atrial fibrillation.

PubMed

Shibazaki, Kensaku; Kimura, Kazumi; Aoki, Junya; Saji, Naoki; Sakai, Kenichiro

2013-08-15

The aim of this study was to investigate whether early initiation of new oral anticoagulants (NOAC) for acute stroke or transient ischemic attack (TIA) patients with nonvalvular atrial fibrillation (NVAF) are safe. Between March 2011 and September 2012, stroke or TIA patients with NVAF who started NOAC within 2 weeks were enrolled retrospectively. Symptomatic intracerebral hemorrhage (ICH), hemorrhagic transformation (HT) on T2*-weighted MRI, recurrence of stroke or TIA, systemic embolism and any bleeding complications after initiation of NOAC were evaluated. 41 patients (25 males; mean age 76.2 years) started NOAC; of which, 39 (95%) patients had stroke, and 2 (5%) had TIA. The median (interquartile range) interval from onset to treatment with NOAC was 2 (1-6) days. Symptomatic ICH was not observed. HT on initial T2* and new HT on follow-up T2* were 5 (12%) and 11 (31%), but it was asymptomatic. Of 5 patients who had HT on the initial T2*, enlargement of hemorrhage on follow-up T2* (hemorrhagic infarction (HI) Type 1→HI Type 2) was observed in 1 patient, but it was asymptomatic. None of the patients had recurrent stroke or TIA, systemic embolism, and any bleeding complications. The NOAC may be safe in acute stroke or TIA patients with NVAF. A large, prospective study is needed to confirm this. Copyright © 2013 Elsevier B.V. All rights reserved.

Major Bleeding Risk During Anticoagulation with Warfarin, Dabigatran, Apixaban, or Rivaroxaban in Patients with Nonvalvular Atrial Fibrillation.

PubMed

Adeboyeje, Gboyega; Sylwestrzak, Gosia; Barron, John J; White, Jeff; Rosenberg, Alan; Abarca, Jacob; Crawford, Geoffrey; Redberg, Rita

2017-09-01

The use of non-vitamin K oral anticoagulants (NOACs) has increased steadily following marketing approval; however, their relative safety in nonvalvular atrial fibrillation (NVAF) patients in real-world clinical practice remains unclear. To compare the risk of major bleeding during anticoagulation therapy between warfarin and NOACs. This retrospective cohort study analyzed administrative claims data on new NVAF users of warfarin, dabigatran, apixaban, or rivaroxaban in routine clinical care from November 2010 to February 2015 in a commercially insured population in the United States. The primary outcome was time to first major bleeding event requiring hospitalization. Patients were followed until discontinuation or switch of anticoagulants, health plan disenrollment, death, or end of study. All patient characteristics were balanced after propensity score inverse probability of treatment (IPT) weighting. Event rates by type of anticoagulant exposure were compared using IPT-weighted Cox proportional hazards models. The study cohort comprised 44,057 patients who used warfarin (n = 23,431), dabigatran (n = 8,539), apixaban (n = 3,689), and rivaroxaban (n = 8,398). Overall mean (SD) age was 70 (12) years, and 41% of the patients were women. A total of 2,337 major bleeding events occurred during 36,636.2 person-years of follow-up. The unadjusted rate of major bleeding with warfarin was 6.0 per 100 person-years versus 2.8 with dabigatran, 3.3 with apixban, and 5.0 with rivaroxaban. Relative to warfarin, major bleeding risk was lower with dabigatran (HR = 0.67, 95% CI = 0.60-0.76) and apixaban (HR = 0.52, 95% CI = 0.41-0.67). Compared with rivaroxaban, major bleeding risk was also lower with dabigatran (HR = 0.67, 95% CI = 0.58-0.78) and apixaban (HR = 0.52, 95% CI = 0.40-0.68). Major bleeding risk was similar for rivaroxaban and warfarin. Relative to apixaban, dabigatran was associated with a significantly higher risk of major gastrointestinal bleeding (HR = 1.43, 95% CI = 1.09-1.88). Study results were consistent with safety findings from pivotal clinical trials comparing NOACs with warfarin and added the perspective of a large real-world observational study that compared bleeding risks associated with NOACs during anticoagulation therapy. Apixaban and dabigatran were associated with lower major bleeding risk compared with warfarin or rivaroxaban; however, apixaban had a lower risk of major gastrointestinal bleeding than dabigatran. These findings can help inform the choice of an optimal agent, which must balance effectiveness and bleeding risk in complex patients. This study was funded by Anthem. Adeboyeje, Sylwestrzak, and Barron are employees of HealthCore, a wholly owned and independently operated subsidiary of Anthem. White, Rosenberg, Abarca, and Crawford are employees of Anthem. Study concept and design were primarily contributed by Adeboyeje and Sylwestrzak, along with the other authors. Adeboyeje took the lead in data collection, along with Sylwestrzak and Barron. Data interpretation was performed primarily by Rosenberg, Crawford, and Redberg, with assistance from the other authors. The manuscript was written by all the authors and revised primarily by White, Abarca, and Redberg, along with the other authors.

Efficacy and safety of a pharmacist-managed inpatient anticoagulation service for warfarin initiation and titration.

PubMed

Wong, Y M; Quek, Y-N; Tay, J C; Chadachan, V; Lee, H K

2011-10-01

Anticoagulation consultations provided by a pharmacist-staffed inpatient service, similar to the experience reported in outpatient anticoagulation clinics, can potentially improve anticoagulation control and outcomes. At Tan Tock Seng Hospital, a 1200-bed acute care teaching hospital in Singapore, pharmacist-managed anticoagulation clinics have been in place since 1997. Pharmacist-managed services were extended to inpatient consultations in anticoagulation management from April 2006. Our objective was to assess the effect of implementing a pharmacist-managed inpatient anticoagulation service. This was a single-centre cohort study. Baseline data from 1 January 2006 to 31 March 2006 were collected and compared with post-implementation data from 1 April 2006 to 31 March 2007. Patients newly started on warfarin for deep vein thrombosis, pulmonary embolism or atrial fibrillation in general medicine and surgery departments were included. The three endpoints were as follows: (i) percentage of international normalized ratios (INRs) achieving therapeutic range within 5 days, (ii) INRs more than 4 during titration and (iii) subtherapeutic INRs on discharge. A total of 26 patients in the control period were compared with 144 patients who had received dosing consultations by a pharmacist during the initiation of warfarin. The provision of pharmacist consult resulted in 88% compared to 38% (P < 0·001) of INR values achieving therapeutic range within 5 days. There was a reduction in INR values of more than 4 during titration from 27% to 2% (P < 0·001), and subtherapeutic INR values on discharge without low molecular weight heparin from 15% to 0% (P < 0·001). The mean time to therapeutic INR was reduced from 6·5 to 3·9 days (P < 0·001) and mean length of stay after initiation of warfarin from 11 to 7·7 days (P = 0·004). Inpatient anticoagulation care and outcomes were significantly improved by a pharmacist-managed anticoagulation service. The time to therapeutic INR was achieved appropriately and efficiently without compromising patient's safety. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Contemporary Management of Atrial Fibrillation: Update on Anticoagulation and Invasive Management Strategies

PubMed Central

Crandall, Mark A.; Bradley, David J.; Packer, Douglas L.; Asirvatham, Samuel J.

2009-01-01

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Its increasing prevalence, particularly among the elderly, renders it one of the most serious current medical epidemics. Several management questions confront the clinician treating a patient with AF: Should the condition be treated? Is the patient at risk of death or serious morbidity as a result of this diagnosis? If treatment is necessary, is rate control or rhythm control superior? Which patients need anticoagulation therapy, and for how long? This review of articles obtained by a search of the PubMed and MEDLINE databases presents the available evidence that can guide the clinician in answering these questions. After discussing the merits of available therapy, including medications aimed at controlling rate, rhythm, or both, we focus on the present status of ablative therapy for AF. Catheter ablation, particularly targeting the pulmonary veins, is being increasingly performed, although the precise indications for this approach and its effectiveness and safety are being actively investigated. We briefly discuss other invasive options that are less frequently used, such as pacemakers, defibrillators, left atrial appendage closure devices, and the surgical maze procedure. PMID:19567719

Transcatheter closure of the left atrial appendage: initial experience with the WATCHMAN device

PubMed Central

Ding, Jiandong; Zhu, Jian; Lu, Jing; Ding, Xiuxia; Zhang, Xiaoli; Lu, Wenbin; Ao, Mingqiang; Ma, Genshan

2015-01-01

Background: Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia, accounting for approximately one third of hospitalizations for cardiac rhythm disturbance. In patients with non-valvular AF, approximately 90% of thrombi are thought to arise from the left atrial appendage (LAA). Anticoagulation with warfarin has been the mainstay of therapy to reduce stroke risk in these patients; however, it is not without its complications including bleeding and drug interactions. Percutaneous left atrial appendage closure can be an alternative to warfarin treatment in patients with AF at high risk for thromboembolic events and/or bleeding complications. Methods: Patients with atrial fibrillation and CHADSVASc score ≥ 2, not eligible for anticoagulation, were submitted to left atrial appendage closure using the WATCHMAN device. The procedure was performed under general anaesthesia, and was guided by fluoroscopy and transoesophageal echocardiography. Results: Percutaneous LAA closure with the WATCHMAN device was performed in all patients. At 45-day follow-up no recurrent major adverse events and especially no thromboembolic events occurred. Conclusions: Transcatheter closure of the LAA with the WATCHMAN device is generally safe and feasible. Long-term follow-up will further reveal the risk and benefits of this therapy. PMID:26629008

Patient-reported treatment satisfaction and budget impact with rivaroxaban vs. standard therapy in elective cardioversion of atrial fibrillation: a post hoc analysis of the X-VeRT trial

PubMed Central

Hohnloser, Stefan H.; Cappato, Riccardo; Ezekowitz, Michael D.; Evers, Thomas; Sahin, Kurtulus; Kirchhof, Paulus; Meng, Isabelle Ling; van Eickels, Martin; Camm, A. John

2016-01-01

Abstract Aims We compared patient-reported treatment satisfaction and the economic impact of anticoagulation therapy with rivaroxaban vs. vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation undergoing elective cardioversion procedures. Methods and results The current study is a post hoc analysis of the prospective, multicentre X-VeRT (EXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in subjects with non-valvular aTrial fibrillation scheduled for cardioversion) trial. Patient-reported treatment satisfaction with anticoagulation therapy was assessed using the Treatment Satisfaction Questionnaire for Medication version II in seven countries (US, UK, Canada, Germany, France, Italy, and the Netherlands). An economic model was also developed to estimate the impact of postponed cardioversions for two countries (UK and Italy). This model estimated the total costs of cardioversion, taking into consideration the costs for drug therapy (including extended treatment duration due to cardioversion postponement), international normalized ratio monitoring of VKAs, the cardioversion procedure, and rescheduling the procedure. These costs were linked to the respective X-VeRT study data to estimate the total costs. Patients receiving rivaroxaban in the delayed cardioversion group had significantly higher scores for Convenience, Effectiveness, and Global satisfaction (81.74 vs. 65.78; 39.41 vs. 32.95; and 82.07 vs. 66.74, respectively; P < 0.0001). Based on the total patient population included in the treatment satisfaction substudy (n = 632) in the delayed cardioversion group in X-VeRT, the use of rivaroxaban was estimated to result in a saving of £421 and €360 per patient in UK and Italian settings, respectively. Conclusion The use of rivaroxaban in the setting of cardioversion resulted in greater patient satisfaction and cost savings, compared with that of VKA. PMID:26487668

Atrial Fibrillation Burden: Moving Beyond Atrial Fibrillation as a Binary Entity: A Scientific Statement From the American Heart Association.

PubMed

Chen, Lin Y; Chung, Mina K; Allen, Larry A; Ezekowitz, Michael; Furie, Karen L; McCabe, Pamela; Noseworthy, Peter A; Perez, Marco V; Turakhia, Mintu P

2018-05-15

Our understanding of the risk factors and complications of atrial fibrillation (AF) is based mostly on studies that have evaluated AF in a binary fashion (present or absent) and have not investigated AF burden. This scientific statement discusses the published literature and knowledge gaps related to methods of defining and measuring AF burden, the relationship of AF burden to cardiovascular and neurological outcomes, and the effect of lifestyle and risk factor modification on AF burden. Many studies examine outcomes by AF burden classified by AF type (paroxysmal versus nonparoxysmal); however, quantitatively, AF burden can be defined by longest duration, number of AF episodes during a monitoring period, and the proportion of time an individual is in AF during a monitoring period (expressed as a percentage). Current guidelines make identical recommendations for anticoagulation regardless of AF pattern or burden; however, a review of recent evidence suggests that higher AF burden is associated with higher risk of stroke. It is unclear whether the risk increases continuously or whether a threshold exists; if a threshold exists, it has not been defined. Higher burden of AF is also associated with higher prevalence and incidence of heart failure and higher risk of mortality, but not necessarily lower quality of life. A structured and comprehensive risk factor management program targeting risk factors, weight loss, and maintenance of a healthy weight appears to be effective in reducing AF burden. Despite this growing understanding of AF burden, research is needed into validation of definitions and measures of AF burden, determination of the threshold of AF burden that results in an increased risk of stroke that warrants anticoagulation, and discovery of the mechanisms underlying the weak temporal correlations of AF and stroke. Moreover, developments in monitoring technologies will likely change the landscape of long-term AF monitoring and could allow better definition of the significance of changes in AF burden over time. © 2018 American Heart Association, Inc.

Impact of co-morbidities and patient characteristics on international normalized ratio control over time in patients with nonvalvular atrial fibrillation.

PubMed

Nelson, Winnie W; Choi, Jiyoon C; Vanderpoel, Julie; Damaraju, Chandrasekharra V; Wildgoose, Peter; Fields, Larry E; Schein, Jeffrey R

2013-08-15

This study determined the association between co-morbidities, including heart failure (HF) and time in therapeutic range (TTR), in patients with nonvalvular atrial fibrillation. Longitudinal patient-level anticoagulation management records collected from 2006 to 2010 were analyzed. Adult patients with nonvalvular atrial fibrillation who used warfarin for a 12-month period with no gap of >60 days between visits were identified. TTR <55% was defined as "lower" TTR. CHADS₂ score of ≥2 was defined as "higher" CHADS₂. Logistic regression analyses were conducted to determine the association between co-morbidities and TTR. A total of 23,425 patients met the study criteria. The mean age ± SD was 74.8 ± 9.7 years, with 84.8% aged ≥65 years. The most common co-morbidities were hypertension (41.7%), diabetes (24.1%), HF (11.7%), and previous stroke (11.1%). The mean TTR ± SD was 67.3 ± 14.4%, with 18.6% of patients in the lower TTR range. In multivariate analyses using age, gender, hypertension, diabetes, stroke, and region as covariates, HF (adjusted odds ratio [OR] 1.41, 95% confidence interval [CI] 1.28 to 1.56; p <0.001), diabetes (OR 1.28, 95% CI 1.19 to 1.38; p <0.001), and previous stroke (OR 1.15, 95% CI 1.04 to 1.27; p <0.001) were associated with lower TTR. In a second set of multivariate analyses using gender and region as covariates, a higher CHADS₂ score was associated with lower TTR (OR 1.11, 95% CI 1.04 to 1.18; p <0.001). In conclusion, HF was associated with the greatest likelihood of a lower TTR, followed by diabetes, then stroke. Anticoagulation control may be more challenging for patients with these conditions. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study.

PubMed

Baumgartner, Christine; Fan, Dongjie; Fang, Margaret C; Singer, Daniel E; Witt, Daniel M; Schmelzer, John R; Williams, Marc S; Gurwitz, Jerry H; Sung, Sue Hee; Go, Alan S

2018-04-14

Anxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes. The Cardiovascular Research Network WAVE (Community-Based Control and Persistence of Warfarin Therapy and Associated Rates and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous Thromboembolism) Study included adults with AF newly starting warfarin between 2004 and 2007 within 5 health delivery systems in the United States. Diagnosed anxiety and depression and other patient characteristics were identified from electronic health records. We identified stroke and bleeding outcomes from hospitalization databases using validated International Classification of Diseases, Ninth Revision ( ICD-9 ), codes. We used multivariable Cox regression to assess the relation between anxiety and/or depression with outcomes after adjustment for stroke and bleeding risk factors. In 25 570 adults with AF initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52 events per 100 person-years). In multivariable analyses, diagnosed anxiety was associated with a higher adjusted rate of combined ischemic stroke and intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28). Results were not materially changed after additional adjustment for patient-level percentage of time in therapeutic anticoagulation range on warfarin (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36). In contrast, neither isolated depression nor combined depression and anxiety were significantly associated with outcomes. Diagnosed anxiety was independently associated with increased risk of combined ischemic stroke and intracranial hemorrhage in adults with AF initiating warfarin that was not explained by differences in risk factors or achieved anticoagulation quality. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Discrepancies between the use of MDRD-4 IDMS and CKD-EPI equations, instead of the Cockcroft-Gault equation, in the determination of the dosage of direct oral anticoagulants in patients with non-valvular atrial fibrillation.

PubMed

Pérez Cabeza, Alejandro Isidoro; Chinchurreta Capote, Pedro Antonio; González Correa, Jose Antonio; Ruiz Mateas, Francisco; Rosas Cervantes, Gabriel; Rivas Ruiz, Francisco; Valle Alberca, Almudena; Bravo Marqués, Rafael

2018-02-09

Direct oral anticoagulants (DOACs) require dose adjustment according to estimated clearance creatinine (eClCr) using the Cockcroft-Gault (CG) equation. There are discrepancies with the equations that estimate glomerular filtration rate (eGFR). We analyse how the use of the CKD-EPI and MDRD-4 IDMS equations affect the recommended dosage for ACODs. Retrospective study of patients with non-valvular atrial fibrillation seen at a cardiology clinic between November 2012 and August 2014. Patients were reclassified according to the recommended dosage for dabigatran, rivaroxaban, apixaban and edoxaban, based on the eGFR equation used. Other clinical factors are taken into account, according to the product label. We analysed the percentage of discordance. Four hundred and fifty-four patients, 53.3% men, with a mean age of 68.7±13.8 years were studied. The mean intra-individual differences recorded for the CG equation were 3.9ml/min/1.73m 2 with MDRD-4 IDMS (95% CI 1.4-6.4, P=.003) and 11.3ml/min/1.73m 2 with CKD-EPI (95% CI 8.9-13.7, P<.001). A gradient is observed in the discordance of the posology (apixaban 1.1%, dabigatran 3.5%, edoxaban 5.7%, rivaroxaban 8.4% with MDRD-4 IDMS). Differences were limited to patients with eClCr<60ml/min and were more evident in≥75 years in which the eGFR equations overestimate renal function. In patients with non-valvular atrial fibrillation, especially with renal failure and in the elderly, eGFR equations tend to overestimate renal function relative to CG and therefore suggest an overdose of DOACs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Patient-reported treatment satisfaction and budget impact with rivaroxaban vs. standard therapy in elective cardioversion of atrial fibrillation: a post hoc analysis of the X-VeRT trial.

PubMed

Hohnloser, Stefan H; Cappato, Riccardo; Ezekowitz, Michael D; Evers, Thomas; Sahin, Kurtulus; Kirchhof, Paulus; Meng, Isabelle Ling; van Eickels, Martin; Camm, A John

2016-02-01

We compared patient-reported treatment satisfaction and the economic impact of anticoagulation therapy with rivaroxaban vs. vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation undergoing elective cardioversion procedures. The current study is a post hoc analysis of the prospective, multicentre X-VeRT (EXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in subjects with non-valvular aTrial fibrillation scheduled for cardioversion) trial. Patient-reported treatment satisfaction with anticoagulation therapy was assessed using the Treatment Satisfaction Questionnaire for Medication version II in seven countries (US, UK, Canada, Germany, France, Italy, and the Netherlands). An economic model was also developed to estimate the impact of postponed cardioversions for two countries (UK and Italy). This model estimated the total costs of cardioversion, taking into consideration the costs for drug therapy (including extended treatment duration due to cardioversion postponement), international normalized ratio monitoring of VKAs, the cardioversion procedure, and rescheduling the procedure. These costs were linked to the respective X-VeRT study data to estimate the total costs. Patients receiving rivaroxaban in the delayed cardioversion group had significantly higher scores for Convenience, Effectiveness, and Global satisfaction (81.74 vs. 65.78; 39.41 vs. 32.95; and 82.07 vs. 66.74, respectively; P < 0.0001). Based on the total patient population included in the treatment satisfaction substudy (n = 632) in the delayed cardioversion group in X-VeRT, the use of rivaroxaban was estimated to result in a saving of £421 and €360 per patient in UK and Italian settings, respectively. The use of rivaroxaban in the setting of cardioversion resulted in greater patient satisfaction and cost savings, compared with that of VKA. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

The complexity of atrial fibrillation newly diagnosed after ischemic stroke and transient ischemic attack: advances and uncertainties

PubMed Central

Cerasuolo, Joshua O.; Cipriano, Lauren E.; Sposato, Luciano A.

2017-01-01

Purpose of review Atrial fibrillation is being increasingly diagnosed after ischemic stroke and transient ischemic attack (TIA). Patient characteristics, frequency and duration of paroxysms, and the risk of recurrent ischemic stroke associated with atrial fibrillation detected after stroke and TIA (AFDAS) may differ from atrial fibrillation already known before stroke occurrence. We aim to summarize major recent advances in the field, in the context of prior evidence, and to identify areas of uncertainty to be addressed in future research. Recent findings Half of all atrial fibrillations in ischemic stroke and TIA patients are AFDAS, and most of them are asymptomatic. Over 50% of AFDAS paroxysms last less than 30 s. The rapid initiation of cardiac monitoring and its duration are crucial for its timely and effective detection. AFDAS comprises a heterogeneous mix of atrial fibrillation, possibly including cardiogenic and neurogenic types, and a mix of both. Over 25 single markers and at least 10 scores have been proposed as predictors of AFDAS. However, there are considerable inconsistencies across studies. The role of AFDAS burden and its associated risk of stroke recurrence have not yet been investigated. Summary AFDAS may differ from atrial fibrillation known before stroke in several clinical dimensions, which are important for optimal patient care strategies. Many questions remain unanswered. Neurogenic and cardiogenic AFDAS need to be characterized, as it may be possible to avoid some neurogenic cases by initiating timely preventive treatments. AFDAS burden may differ in ischemic stroke and TIA patients, with distinctive diagnostic and treatment implications. The prognosis of AFDAS and its risk of recurrent stroke are still unknown; therefore, it is uncertain whether AFDAS patients should be treated with oral anticoagulants. PMID:27984303

Atrial fibrillation among African Americans, Hispanics and Caucasians: clinical features and outcomes from the AFFIRM trial.

PubMed

Bush, David; Martin, Lisa W; Leman, Robert; Chandler, Mary; Haywood, L Julian

2006-03-01

The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study concluded that rate control with anticoagulation was equivalent overall to rhythm control with cardioversion for long-term survival and that anticoagulation reduced the risk of stroke. We compared baseline and follow-up data for three ethnic groups: Caucasians (n=3,599), African Americans (n=265) and Hispanics (n=132). Caucasians were older and more likely male, African Americans were more likely female and hypertensive, and Hispanics had higher prevalence of cardiomyopathy. Survival was better for rate control than rhythm control in Caucasians, equivalent in African Americans and better for rhythm control in Hispanics. Outcomes may be influenced by differential baseline characteristics, but low numbers of African Americans and Hispanics warrant caution in data interpretation. The AFFIRM study compared a rate-control strategy to a rhythm-control strategy for the treatment of atrial fibrillation (AF) in patients at high risk for stroke or death. It concluded that the rhythm-control strategy offered no survival advantage, and it also confirmed the value of anticoagulation to prevent complications of AF. Data have not previously been available for specific racial ethnic populations. We compared baseline and follow-up data for the patients randomized to rate-control versus rhythm-control in three population groups-Caucasian, African-American and Hispanic. Among 4,060 total patients, 3,599 were Caucasian, 265 were African-American and 132 were Hispanic. At baseline, Caucasians were older and had a higher percentage of males, normal ejection fractions, AF as their only cardiac diagnosis, a prior antiarrhythmic drug failure and less congestive heart failure. African Americans were more likely to be female, had more hypertension and qualified for the study with a first episode of AF, compared to Caucasians. Hispanics had more cardiomyopathy at baseline than Caucasians. Overall survival in Caucasians at five years for the rate-control and rhythm-control groups was 78.9% vs. 76.4%, respectively (p=0.04); for African Americans, 79.0% vs. 69.4% (p=0.22); and for Hispanics, 66.5% vs. 83.9% (p=0.01). Overall, survival was not different between the three populations. However, lower rates of event-free survival were recorded for Hispanics and for African Americans (p=0.0182). Different survival rates were found for rate-control versus rhythm-control in African-American and Hispanic patients, compared to Caucasian. These findings may be influenced by differences in baseline characteristics, but must be interpreted with caution because of the small sample sizes for African-American and Hispanic participants.

Stroke prevention in atrial fibrillation: re-defining 'real-world data' within the broader data universe.

PubMed

Fanaroff, Alexander C; Steffel, Jan; Alexander, John H; Lip, Gregory Y H; Califf, Robert M; Lopes, Renato D

2018-04-23

Real-world data (RWD) has been defined as data generated outside of traditional randomized clinical trials (RCTs). Though RWD has received increasing attention from regulatory authorities and professional societies, dividing evidence into that derived from 'real-world' vs. 'non-real-world' sources provides only one element of a much larger framework for evidence evaluation. Evidence should be evaluated on the source of the data, the method of treatment allocation (whether any intervention being evaluated was assigned or simply observed as used in practice) and the context in which the evidence was generated (overall study design). Under this framework, RWD refers only to data source, and a study incorporates RWD when it primarily uses data collected for non-research purposes, such as insurance claims data or the electronic health record, regardless of study design. Separation of study design, data source, and context enables parallel evaluation of two critical elements: (i) whether a study can support claims of causal inference, which can be assured with a high degree of confidence only in studies where patients are assigned treatments by protocol; and (ii) whether the study population and clinical context mirror clinical practice, a strength of observational studies using data from clinical practice or administrative claims. In this review, we describe the strengths and weaknesses of observational and non-observational studies, and studies involving RWD and non-RWD, through the lens of anticoagulation for atrial fibrillation (AF). Observational studies employing RWD are useful for describing how oral anticoagulants are used in clinical practice, but generally cannot be used to make claims regarding comparative treatment effects. Questions regarding treatment effect generally are best answered through an RCT, and additional pragmatic RCTs are needed to compare different antithrombotic agents for the prevention of thrombotic events in AF.

Inadequate anticoagulation by Vitamin K Antagonists is associated with Major Adverse Cardiovascular Events in patients with atrial fibrillation.

PubMed

Pastori, Daniele; Pignatelli, Pasquale; Saliola, Mirella; Carnevale, Roberto; Vicario, Tommasa; Del Ben, Maria; Cangemi, Roberto; Barillà, Francesco; Lip, Gregory Y H; Violi, Francesco

2015-12-15

Time in therapeutic range (TTR) reflects the quality of anticoagulation and is inversely correlated with ischemic stroke in atrial fibrillation (AF) patients. Few data on the relationship between TTR and myocardial infarction (MI) are available. We investigated the association between TTR and Major Adverse Cardiovascular Events (MACE) in a cohort of anticoagulated AF patients. We calculated TTR for 627 AF patients on vitamin K antagonists, who were followed for a median of 30.8 months (1755 patients/year). The primary outcome was a combined endpoint of MACE including fatal/nonfatal MI and cardiovascular death. Mean age was 73.3 (±8.2) years, and 40.2% were women. During follow-up, we recorded 67 events: 19 stroke/TIA (1.1%/year) and 48 MACE (2.9%/year): 24 MI and 24 cardiovascular deaths. The cohort was categorized according to tertiles of TTR values: TTR 13-58%, 59-74%, and 75-100%. There was a significant increased rate of MACE across tertiles of TTR (Log-Rank test: p<0.001). On Cox proportion hazard analysis, the 2nd vs. 1st tertile of TTR (p=0.002, hazard ratio [HR] 0.347, confidence interval [CI] 95% 0.177-0.680), 3rd vs. 1st tertile of TTR (p<0.001, HR 0.164, CI 95% 0.067-0.402), age (p<0.001, HR 1.094, CI 95% 1.042-1.148), history of stroke/TIA (p=0.015, HR 2.294, CI 95% 1.172-4.490) and smoking (p=0.003, HR 3.450, CI 95% 1.532-7.769) predicted MACE. TTR was an independent predictor of MACE in our cohort of AF patients. Our findings suggest that a good anticoagulation control is necessary to reduce not only the risk of stroke but also that of MACE. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Risk of Myocardial Infarction in Patients with Long-Term Non-Vitamin K Antagonist Oral Anticoagulant Treatment.

PubMed

Tornyos, Adrienn; Kehl, Dániel; D'Ascenzo, Fabrizio; Komócsi, András

2016-01-01

The relative cardiovascular (CV) safety of oral anticoagulants continues to be debated, and in particular concerns for risk of myocardial infarction (MI) have been raised. We analyzed the risk of MI in patients treated long term with oral anticoagulants (vitamin K antagonists [VKA], direct thrombin inhibitors or activated X factor antagonist) for atrial fibrillation, deep vein thrombosis or pulmonary embolism using a network meta-analysis (NMA). Randomized, phase 3 trials comparing novel anticoagulants to VKA were searched. Information on study design and clinical outcomes was extracted. The primary end-point of the analysis was the occurrence of MI or acute coronary syndrome. A Bayesian multiple treatment analysis was performed using fixed-effect and random-effects modeling. Twelve trials including 100,524 randomized patients were analyzed. The odds for MI in NMA were worse with dabigatran when compared to VKA, rivaroxaban, apixaban, and edoxaban (OR: 0.66 CI: 0.49-0.87; OR: 0.56 CI: 0.38-0.82, OR: 0.59 CI 0.40-0.88, and OR: 0.71 CI: 0.50-1.0, respectively).The posterior probability of being the first best choice of treatment was 53.5% for rivaroxaban, 33.8% for apixaban, 9.5% for ximelagatran, 2.0% for edoxaban, 1.2% for VKA, and 0.007% for dabigatran. There is a considerable heterogeneity regarding CV safety among oral anticoagulants. Differences in risk of MI may influence the choice of treatment. Multiple treatment NMA found 29%-44% higher odds of MI with dabigatran supporting the concerns regarding its CV safety. Copyright © 2015 Elsevier Inc. All rights reserved.

Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices.

PubMed

Martin, David T; Bersohn, Malcolm M; Waldo, Albert L; Wathen, Mark S; Choucair, Wassim K; Lip, Gregory Y H; Ip, John; Holcomb, Richard; Akar, Joseph G; Halperin, Jonathan L

2015-07-07

Atrial tachyarrhythmias (ATs) detected by implanted devices are often atrial fibrillation or flutter (AF) associated with stroke. We hypothesized that introduction and termination of anticoagulation based upon AT monitoring would reduce both stroke and bleeding. We randomized 2718 patients with dual-chamber and biventricular defibrillators to start and stop anticoagulation based on remote rhythm monitoring vs. usual office-based follow-up with anticoagulation determined by standard clinical criteria. The primary analysis compared the composite endpoint of stroke, systemic embolism, and major bleeding with the two strategies. The trial was stopped after 2 years median follow-up based on futility of finding a difference in primary endpoints between groups. A total of 945 patients (34.8%) developed AT, 264 meeting study anticoagulation criteria. Adjudicated atrial electrograms confirmed AF in 91%; median time to initiate anticoagulation was 3 vs. 54 days in the intervention and control groups, respectively (P < 0.001). Primary events (2.4 vs. 2.3 per 100 patient-years) did not differ between groups (HR 1.06; 95% CI 0.75-1.51; P = 0.732). Major bleeding occurred at 1.6 vs. 1.2 per 100 patient-years (HR 1.39; 95% CI 0.89-2.17; P = 0.145). In patients with AT, thromboembolism rates were 1.0 vs. 1.6 per 100 patient-years (relative risk -35.3%; 95% CI -70.8 to 35.3%; P = 0.251). Although AT burden was associated with thromboembolism, there was no temporal relationship between AT and stroke. In patients with implanted defibrillators, the strategy of early initiation and interruption of anticoagulation based on remotely detected AT did not prevent thromboembolism and bleeding. IMPACT ClinicalTrials.gov identifier: NCT00559988 ( http://clinicaltrials.gov/ct2/show/NCT00559988?term=NCT00559988&rank=1 ). Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

The influence of residual apixaban on bleeding complications during and after catheter ablation of atrial fibrillation.

PubMed

Mukai, Yutaro; Wada, Kyoichi; Miyamoto, Koji; Nakagita, Kazuki; Fujimoto, Mai; Hosomi, Kouichi; Kuwahara, Takeshi; Takada, Mitsutaka; Kusano, Kengo; Oita, Akira

2017-10-01

The periprocedural protocol for atrial fibrillation (AF) ablation commonly includes anticoagulation therapy. Apixaban, a direct oral anticoagulant, is currently approved for clinical use; however, little is known about the effects of residual apixaban concentration on bleeding complications during/after AF ablation. Therefore, we measured residual apixaban concentration by using mass spectrometry and examined the anticoagulant's residual effects on bleeding complications. Fifty-eight patients (Mean age of 64.7±12.5 years; 31 males, 27 females) were enrolled and administered apixaban twice daily. We analyzed trough apixaban concentration, activated clotting time (ACT), heparin dose, and bleeding complications during/after AF ablation. Apixaban concentrations were directly measured using mass spectrometry. Bleeding complications were observed in 19 patients (delayed hemostasis at the puncture site, 16; hematuria, 3; hemosputum, 1). No patient required blood transfusion. The mean trough apixaban concentration was significantly lower in patients with bleeding complications than without (152.4±73.1 vs. 206.8±98.8 ng/mL respectively, P =0.037), while the heparin dose to achieve ACT>300 s was significantly higher in patients with bleeding complications (9368.4±2929.0 vs. 7987.2±2135.2 U/body respectively, P =0.046). Interestingly, a negative correlation was found between the trough apixaban concentration and the heparin dose to achieve ACT>300 s ( P =0.033, R=-0.281). Low residual plasma apixaban is associated with a higher incidence of bleeding complications during/after AF ablation, potentially because of a greater heparin requirement during AF ablation.

Is there a role for pharmacokinetic/pharmacodynamic-guided dosing for novel oral anticoagulants?

PubMed

Chan, Noel; Sager, Philip T; Lawrence, Jack; Ortel, Thomas's; Reilly, Paul; Berkowitz, Scott; Kubitza, Dagmar; Eikelboom, John; Florian, Jeffry; Stockbridge, Norman; Rose, Martin; Temple, Robert; Seltzer, Jonathan H

2018-05-01

The novel direct oral anticoagulants (NOACs) represent a major advance in oral anticoagulant therapy and are replacing vitamin K antagonists as the preferred options for many indications. Given in fixed doses without routine laboratory monitoring, they have been shown to be at least as effective in reducing thromboembolic stroke as dose-adjusted warfarin in phase 3 randomized trials and less likely to cause hemorrhagic stroke. Pharmacokinetic and/or pharmacodynamic subanalyses of the major NOAC trials in patients with atrial fibrillation have established relationships between clinical characteristics, and drug levels and/or pharmacodynamic responses with both efficacy and safety. Based on these analyses, pharmaceutical manufacturers and regulatory authorities have provided contraindications and dosing recommendations based on clinical characteristics that are associated with drug levels and/or pharmacodynamic responses, stroke reduction, and bleeding risk to optimize the risk-benefit profile of the NOACs in the real world. The current fixed-dosing strategy of NOACs has triggered discussions about the potential value of laboratory monitoring and dose adjustment in customizing drug exposure to further improve the safety and efficacy of the NOACs in patients with atrial fibrillation. As there is neither high-quality evidence nor consensus about the potential role of laboratory monitoring and dose adjustment for the NOACs, a Cardiac Research Safety Consortium "Think Tank" meeting was held at the American College of Cardiology Heart House in December 2015 to discussions these issues. This manuscript reports on the deliberations and the conclusions reached at that meeting. Copyright © 2017. Published by Elsevier Inc.

Rivaroxaban in the cardiovascular world: a direct anticoagulant useful to prevent stroke and venous and arterial thromboembolism.

PubMed

Seoane, Leonardo; Cortés, Marcia; Aris Cancela, María Esther; Furmento, Juan; Baranchuk, Adrián; Conde, Diego

2018-06-14

Until recently, vitamin K antagonists (VKA) were the only drugs available for long-term anticoagulation. The use of these drugs is laborious due to their variable pharmacokinetics and pharmacodynamics. The advent of direct oral anticoagulants has produced a paradigm shift due to their low incidence of drug interactions, their stable plasma levels, and their lack of monitoring. Rivaroxaban, a factor Xa inhibitor, has been tested in different clinical scenarios and has proved to be effective and safe, even increasing the scope of the old VKA. Areas covered: A non-systematic review of the literature was conducted using the PubMed and Cochrane databases, focusing on randomized clinical trials and real-world observational studies that evaluated rivaroxaban in patients with atrial fibrillation, venous thromboembolism, and atherosclerotic coronary and peripheral vascular disease. Expert commentary: The role of rivaroxaban keeps expanding into areas that were unimaginable few years ago, in the light of solid evidence that has eliminated old strict paradigms. Nonetheless, it will be necessary to adjust costs and better understand the perceived barriers to its widespread implementation, to get fully acceptation of rivaroxaban for the different clinical conditions that have been suggested.

Pulmonary artery perforation by plug anchoring system after percutaneous closure of left appendage.

PubMed

Bianchi, Giacomo; Solinas, Marco; Gasbarri, Tommaso; Bevilacqua, Stefano; Tiwari, Kaushal Kishore; Berti, Sergio; Glauber, Mattia

2013-07-01

Patients receiving oral anticoagulant therapy for atrial fibrillation who are at high risk of bleeding are increasingly referred for percutaneous left atrial appendage exclusion. Although effective, this procedure is not free from risk. We report a case of pericardial tamponade due to pulmonary artery tear caused by a trespassing anchoring hook of an AGA plug. Intraoperatively, no actual bleeding was found from the left appendage, a proof of its complete occlusion by the device. The patient underwent successful surgical repair and radio-frequency ablation of atrial fibrillation was performed by pulmonary veins encircling. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Massive cortico-subcortical ischemic stroke with a consecutive hemorrhagic event: a case report.

PubMed

Pirici, D; Ion, Daniela Adriana; Mogoantă, L; Mărgăritescu, Otilia; Pirici, Ionica; Foarfă, Camelia; Tudorică, Valerica; Panduru, N M; Coconu, Marieta; Checheriţă, I A

2011-01-01

We report a case of a 78-year-old woman with a large cerebral infarction probably due to athermanous embolism following atrial fibrillation. The patient, known with atrial fibrillation, high blood pressure and heart failure, complained of headache and motor impairment on the left side of the body. CT imaging revealed a subacute ischemic lesion in the right fronto-occipital lobes, and an old ischemic lesion in the right fronto-parietal lobes. Anticoagulant treatment was conducted with careful monitoring of the coagulability status. After almost three weeks, suddenly the patient became comatose and died shortly after. Macroscopic and microscopic examination confirmed the cortico-subcortical ischemic lesions, but also identified a fresh hemorrhagic site in pons, distant from the initial lesion sites. An immunohistochemical study identified blood vessels in the ischemic sites completely isolated from any glial support. This is a rare case of a large cerebral infarction with a pontine hemorrhagic event.

Complicated rheumatic mitral stenosis presenting in an elderly patient and the challenges in its management.

PubMed

Ganeshpure, Swapnil; Vaidya, Gaurang Nandkishor; Gattani, Vipul

2012-12-05

A 76 -year-old lady with a recent diagnosis of rheumatic heart disease (RHD), and a history of repeated lower respiratory tract infections, came with symptoms of gastritis unrelated to the primary disease but further diagnostic study in the hospital revealed poorly controlled atrial fibrillation, grossly dilated left atrium with two large left atrial thrombi and mitral valve area<1 cm(2). It was decided that the best approach in our patient would be mitral valve replacement with mechanical prosthesis. Despite the usual trend of using bioprosthesis in the elderly, our decision was influenced by the fact that the patient would need chronic anticoagulation for atrial fibrillation in any case. The purpose of our case presentation is to illustrate a late-presenting case of RHD with unusual associations and the challenges to choose the best possible management.

Development of Interstitial Lung Disease after Initiation of Apixaban Anticoagulation Therapy.

PubMed

Tomari, Shinya; Homma, Kazunari; Noguchi, Teruo; Aiba, Takeshi; Matsuki, Takayuki; Suzuki, Rieko; Koga, Masatoshi; Takigami, Masao; Tagawa, Hiroshi; Hashimoto, Taisuke; Toyoda, Kazunori

2016-07-01

Nonvitamin K antagonist oral anticoagulants may cause interstitial lung disease (ILD) similar to that seen for other cardiovascular drugs. The aim of this study was to determine trends and medical conditions associated with ILD in patients taking apixaban. A single-center observational survey conducted between February 2013 and May 2015 examined patients who developed ILD after initiation of apixaban administration. Chest computed tomography showed that 4 (~.45%) out of approximately 870 apixaban users developed ILD. All patients were elderly Japanese men with decreased creatinine clearance who had nonvalvular atrial fibrillation. Three of the four were confirmed smokers, whereas three had a history of lung disease. Dyspnea occurred during the initial week after starting apixaban administration in 3 patients and at 90 days in 1 patient. All patients underwent methylprednisolone pulse therapy, with three requiring mechanical ventilation. Although 2 patients recovered, the other two died of respiratory failure. Development of ILD during anticoagulation with apixaban is not rare. When apixaban is administered in elderly high-risk patients, subjects need to be carefully monitored for respiratory symptoms. As drug-induced ILD is often reported in Japan, further studies that clarify if these types of cases are common in countries other than Japan will also need to be undertaken. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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.

Adherence to oral anticoagulants in patients with atrial fibrillation-a population-based retrospective cohort study linking health information systems in the Valencia region, Spain: a study protocol.

PubMed

Sanfélix-Gimeno, G; Rodríguez-Bernal, C L; Hurtado, I; Baixáuli-Pérez, C; Librero, J; Peiró, S

2015-10-19

Adherence to oral anticoagulation (OAC) treatment, vitamin K antagonists or new oral anticoagulants, is an essential element for effectiveness. Information on adherence to OAC in atrial fibrillation (AF) and the impact of adherence on clinical outcomes using real-world data barely exists. We aim to describe the patterns of adherence to OAC over time in patients with AF, estimate the associated factors and their impact on clinical events, and assess the same issues with conventional measures of primary and secondary adherence-proportion of days covered (PDC) and persistence-in routine clinical practice. This is a population-based retrospective cohort study including all patients with AF treated with OAC from 2010 to date in Valencia, Spain; data will be obtained from diverse electronic records of the Valencia Health Agency. adherence trajectories. (1) primary non-adherence; (2) secondary adherence: (a) PDC, (b) persistence. Clinical outcomes: hospitalisation for haemorrhagic or thromboembolic events and death during follow-up. (1) description of baseline characteristics, adherence patterns (trajectory models or latent class growth analysis models) and conventional adherence measures; (2) logistic or Cox multivariate regression models, to assess the associations between adherence measures and the covariates, and logistic multinomial regression models, to identify characteristics associated with each trajectory; (3) Cox proportional hazard models, to assess the relationship between adherence and clinical outcomes, with propensity score adjustment applied to further control for potential confounders; (4) to estimate the importance of different healthcare levels in the variations of adherence, logistic or Cox multilevel regression models. This study has been approved by the corresponding Clinical Research Ethics Committee. We plan to disseminate the project's findings through peer-reviewed publications and presentations at relevant health conferences. Policy reports will also be prepared in order to promote the translation of our findings into policy and clinical practice. 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.

Combined low-dose aspirin and warfarin anticoagulant therapy of postoperative atrial fibrillation following mechanical heart valve replacement.

PubMed

Wang, Jian-tang; Dong, Ming-feng; Song, Guang-min; Ma, Zeng-shan; Ma, Sheng-jun

2014-12-01

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

Use of apixaban after development of suspected rivaroxaban-induced hepatic steatosis; a case report.

PubMed

Anastasia, Emily J; Rosenstein, Robert S; Bergsman, Jeffrey A; Parra, David

2015-09-01

Postmarketing reports have emerged associating rivaroxaban with drug-induced liver injury (DILI); however, management strategies of patients with suspected rivaroxaban-induced liver injury requiring continued anticoagulation have not been published. The present report describes a 67-year-old male with atrial fibrillation receiving rivaroxaban who developed a 16-fold elevation in alanine transaminase, a nearly two-fold elevation in total bilirubin, and ultrasound confirmed hepatic steatosis. The patient was switched from rivaroxaban to apixaban with subsequent rapid resolution of laboratory abnormalities. Rapid improvement in liver function tests despite use of an alternative factor Xa inhibitor suggests that rivaroxaban's mechanism of hepatotoxicity may be unrelated to its pharmacologic action. When using rivaroxaban, clinicians should be aware of the small but potentially serious risk of DILI. Because most anticoagulants have been associated with DILI, selection of an alternative anticoagulant may be challenging; however, the use of apixaban in this case suggests it may be a reasonable alternative.

Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation.

PubMed

Liu, Michelle Y; Ballard, Dustin W; Huang, Jie; Rauchwerger, Adina S; Reed, Mary E; Bouvet, Sean C; Vinson, David R

2018-05-01

Emergency department (ED) patients with acute pulmonary embolism (PE) despite therapeutic anticoagulation at the time of diagnosis are uncommonly encountered and present a diagnostic and management challenge. Their characterization and outcomes are poorly described. We sought to describe the prevalence and characteristics of therapeutically anticoagulated patients among a population of patients with acute PE in a community setting and to describe treatment changes and 30-day outcomes. From a large retrospective cohort of adults with acute, objectively-confirmed PE across 21 EDs between 01/2013 and 04/2015, we identified patients who arrived on direct oral or injectable anticoagulants, or warfarin with an initial ED international normalized ratio (INR) value ≥2.0. Patients were excluded from the larger cohort if they had received a diagnosis of venous thromboembolism (VTE) in the prior 30 days. We gathered demographic and clinical variables from electronic health records and structured manual chart review. We report discharge anticoagulation regimens and major 30-day adverse outcomes. Among 2,996 PE patients, 36 (1.2%) met study criteria. Mean age was 63 years. Eleven patients (31%) had active cancer and 25 (69%) were high risk on the PE Severity Index (Classes III-V), comparable to the larger cohort (p>0.1). Reasons for pre-arrival anticoagulation were VTE treatment or prevention (n=21), and atrial fibrillation or flutter (n=15). All patients arrived on warfarin and one was also on enoxaparin: 32 had a therapeutic INR (2.0-3.0) and four had a supratherapeutic INR (>3.0). Fifteen patients (42%) had at least one subtherapeutic INR (<2.0) in the 14 days preceding their diagnostic visit. Two patients died during hospitalization. Of the 34 ultimately discharged, 22 underwent a change in anticoagulation drug or dosing, 19 of whom received injectables, either to replace or to supplement warfarin. Four patients also received inferior vena cava filters. Thirty-day outcomes included one major hemorrhage and one additional death. No patients experienced recurrent or worsening VTE. We found a low prevalence of therapeutic anticoagulation at the time of acute PE diagnosis. Most patients with breakthrough PE underwent a change in therapy, though management varied widely. Subtherapeutic anticoagulation levels in the preceding weeks were common and support the importance of anticoagulation adherence.

Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation

PubMed Central

Liu, Michelle Y.; Ballard, Dustin W.; Huang, Jie; Rauchwerger, Adina S.; Reed, Mary E.; Bouvet, Sean C.

2018-01-01

Introduction Emergency department (ED) patients with acute pulmonary embolism (PE) despite therapeutic anticoagulation at the time of diagnosis are uncommonly encountered and present a diagnostic and management challenge. Their characterization and outcomes are poorly described. We sought to describe the prevalence and characteristics of therapeutically anticoagulated patients among a population of patients with acute PE in a community setting and to describe treatment changes and 30-day outcomes. Methods From a large retrospective cohort of adults with acute, objectively-confirmed PE across 21 EDs between 01/2013 and 04/2015, we identified patients who arrived on direct oral or injectable anticoagulants, or warfarin with an initial ED international normalized ratio (INR) value ≥2.0. Patients were excluded from the larger cohort if they had received a diagnosis of venous thromboembolism (VTE) in the prior 30 days. We gathered demographic and clinical variables from electronic health records and structured manual chart review. We report discharge anticoagulation regimens and major 30-day adverse outcomes. Results Among 2,996 PE patients, 36 (1.2%) met study criteria. Mean age was 63 years. Eleven patients (31%) had active cancer and 25 (69%) were high risk on the PE Severity Index (Classes III–V), comparable to the larger cohort (p>0.1). Reasons for pre-arrival anticoagulation were VTE treatment or prevention (n=21), and atrial fibrillation or flutter (n=15). All patients arrived on warfarin and one was also on enoxaparin: 32 had a therapeutic INR (2.0–3.0) and four had a supratherapeutic INR (>3.0). Fifteen patients (42%) had at least one subtherapeutic INR (<2.0) in the 14 days preceding their diagnostic visit. Two patients died during hospitalization. Of the 34 ultimately discharged, 22 underwent a change in anticoagulation drug or dosing, 19 of whom received injectables, either to replace or to supplement warfarin. Four patients also received inferior vena cava filters. Thirty-day outcomes included one major hemorrhage and one additional death. No patients experienced recurrent or worsening VTE. Conclusion We found a low prevalence of therapeutic anticoagulation at the time of acute PE diagnosis. Most patients with breakthrough PE underwent a change in therapy, though management varied widely. Subtherapeutic anticoagulation levels in the preceding weeks were common and support the importance of anticoagulation adherence. PMID:29760849

The Perils of Inhibiting Deficient Factors.

PubMed

Sayar, Zara; Speed, Victoria; Patel, Jignesh P; Patel, Raj K; Arya, Roopen

2018-06-08

We report a case of a previously undiagnosed factor X deficiency in an 83-year old man, who had no previous bleeding history despite multiple haemostatic challenges. He was anticoagulated with warfarin for atrial fibrillation (AF) without bleeding complications; however, major haemorrhage occurred soon after a switch to rivaroxaban. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effectiveness and Safety of Dabigatran, Rivaroxaban, and Apixaban Versus Warfarin in Nonvalvular Atrial Fibrillation.

PubMed

Yao, Xiaoxi; Abraham, Neena S; Sangaralingham, Lindsey R; Bellolio, M Fernanda; McBane, Robert D; Shah, Nilay D; Noseworthy, Peter A

2016-06-13

The introduction of non-vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may not translate to routine practice. We aimed to evaluate the effectiveness and safety of dabigatran, rivaroxaban, and apixaban by comparing each agent with warfarin. Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15 390), dabigatran versus warfarin (n=28 614), and rivaroxaban versus warfarin (n=32 350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio [HR] 0.67, 95% CI 0.46-0.98, P=0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76-1.26, P=0.98; rivaroxaban: HR 0.93, 95% CI 0.72-1.19, P=0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban: HR 0.45, 95% CI 0.34-0.59, P<0.001; dabigatran: HR 0.79, 95% CI 0.67-0.94, P<0.01), and rivaroxaban was associated with a similar risk (HR 1.04, 95% CI 0.90-1.20], P=0.60). All non-vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding. In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated with similar risk of stroke but lower risk of major bleeding, and rivaroxaban was associated with similar risks of both stroke and major bleeding in comparison to warfarin. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

PubMed

Roswell, Robert O; Greet, Brian; Shah, Sunny; Bernard, Samuel; Milin, Alexandra; Lobach, Iryna; Guo, Yu; Radford, Martha J; Berger, Jeffrey S

2016-08-01

Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.

Quality of warfarin therapy and risk of stroke, bleeding, and mortality among patients with atrial fibrillation: results from the nationwide FinWAF Registry.

PubMed

Lehto, Mika; Niiranen, Jussi; Korhonen, Pasi; Mehtälä, Juha; Khanfir, Houssem; Hoti, Fabian; Lassila, Riitta; Raatikainen, Pekka

2017-06-01

The most important management strategy in atrial fibrillation (AF) patients is preventing stroke with oral anticoagulants. Warfarin is still used as a first-line anticoagulant, although non-vitamin K antagonist oral anticoagulants are currently recommended to manage AF. Using a large, unselected national sample of AF patients, we evaluated the relationships between quality of warfarin therapy and the risks of thromboembolism, bleeding complications, and mortality. The nationwide FinWAF study included 54 568 AF patients taking warfarin. Time in the therapeutic range (TTR) was calculated on a continuous basis using the Rosendaal method and international normalized ratio values over the previous 60 days. Adjusted Cox proportional hazard models were prepared for different TTR levels and major clinical end points. The mean age of patients was 73.1 years (standard deviation 10.8), and 47% were female. The mean follow-up time was 3.2 ± 1.6 years (median 3.4). In the TTR groups of ≤40%, 60-70%, 70-80%, and >80%, the annual risk of stroke was 9.3%, 4.7%, 4.6%, and 3.1%; bleeding events 7.5%, 4.5%, 4.3%, and 2.6%; and overall mortality 20.9%, 8.5%, 6.4%, and 3.1%, respectively. All differences among the TTR groups were highly significant (p < 0.001). The quality of warfarin treatment was strongly associated with the risk of stroke and the prognosis of AF patients. Patient outcomes continued to improve with increasing TTR values up to a TTR ≥80%; therefore, the target for the TTR should exceed 80% instead of the traditional range of at least 60-70%. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Atrial fibrillation incrementally increases dementia risk across all CHADS2 and CHA2DS2VASc strata in patients receiving long-term warfarin.

PubMed

Graves, Kevin G; May, Heidi T; Jacobs, Victoria; Bair, Tami L; Stevens, Scott M; Woller, Scott C; Crandall, Brian G; Cutler, Michael J; Day, John D; Mallender, Charles; Osborn, Jeffrey S; Peter Weiss, J; Jared Bunch, T

2017-06-01

Patients with atrial fibrillation (AF) are at higher risk for developing dementia. Warfarin is a common therapy for the prevention of thromboembolism in AF, valve replacement, and thrombosis patients. The extent to which AF itself increases dementia risk remains unknown. A total 6030 patients with no history of dementia and chronically anticoagulated with warfarin were studied. Warfarin management was provided through a Clinical Pharmacy Anticoagulation Service. Patients were stratified by warfarin indication of AF (n=3015) and non-AF (n=3015) and matched by propensity score (±0.01). Patients were stratified by the congestive heart failure, hypertension, age >75 years, diabetes, stroke (CHADS 2 ) score calculated at the time of warfarin initiation and followed for incident dementia. The average age of the AF cohort was 69.3±11.2 years, and 52.7% were male; average age of non-AF cohort was 69.3±10.9 years, and 51.5% were male. Increasing CHADS 2 score was associated with increased dementia incidence, P trend=.004. When stratified by warfarin indication, AF patients had an increased risk of dementia incidence. After multivariable adjustment, AF patients continued to display a significantly increased risk of dementia when compared with non-AF patients across all CHADS 2 scores strata. In patients receiving long-term warfarin therapy, dementia risk increased with increasing CHADS 2 scores. However, the presence of AF was associated with higher rates of dementia across all CHADS 2 score strata. These data suggest that AF contributes to the risk of dementia and that this risk is not solely attributable to anticoagulant use. Dementia may be an end manifestation of a systemic disease state, and AF likely contributes to its progression. Copyright © 2017 Elsevier Inc. All rights reserved.

New anticoagulants for the prevention of stroke in atrial fibrillation.

PubMed

Höchtl, Thomas; Huber, Kurt

2012-02-01

Oral anticoagulation in atrial fibrillation is obligatory to lower the risk of spontaneous cerebrovascular and systemic thromboembolism. For this purpose, vitamin K antagonists (coumarins) have been recommended as the most effective drugs for a long time. However, problems with the practical use of these agents, e.g. the need for frequent and regular coagulation controls, the inter-individual differences in maintaining a stable therapeutic range, as well as drug or food interactions, have led to the search and investigation of alternative compounds characterized by a more simple use (e.g. without regular controls of therapeutic levels), high efficacy, as well as low risk of bleeding. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apixaban have recently been investigated to prove whether they fulfill the high expectancy of an ideal anticoagulant with respect to a more favorable efficacy/safety profile and without the need for coagulation controls, thereby improving quality of life. Dabigatran (RE-LY) achieved an impressive reduction in stroke and non-central nervous system (non-CNS) embolism (110 mg: 1.5%/year; 150 mg: 1.1%/year) in contrast to warfarin (1.7%/year; P = 0.34 and P < 0.001) with a favorable action on bleeding hazards. The results of rivaroxaban which were obtained in the ROCKET AF study (on treatment analysis: stroke and non-CNS embolism: 1.7%/year vs. 2.15%/year with warfarin; P = 0.015; primary safety endpoint major and minor bleeding: 14.91 vs. 14.52%; P = 0.442) point in the same direction. And finally, compared to aspirin, apixaban reduced the combined primary efficacy endpoint by 52% with comparable rates of bleeding (AVERROES). This review gives a summary of the current knowledge about these agents and their potential future importance. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Expert consensus of the French Society of Geriatrics and Gerontology and the French Society of Cardiology on the management of atrial fibrillation in elderly people.

PubMed

Hanon, Olivier; Assayag, Patrick; Belmin, Joel; Collet, Jean Philippe; Emeriau, Jean Paul; Fauchier, Laurent; Forette, Françoise; Friocourt, Patrick; Gentric, Armelle; Leclercq, Christophe; Komajda, Michel; Le Heuzey, Jean Yves

2013-05-01

Atrial fibrillation (AF) is a common and serious condition in the elderly. AF affects between 600,000 and one million patients in France, two-thirds of whom are aged above 75 years. AF is a predictive factor for mortality in the elderly and a major risk factor for stroke. Co-morbidities are frequent and worsen the prognosis. The management of AF in the elderly should involve a comprehensive geriatric assessment (CGA), which analyses both medical and psychosocial elements, enabling evaluation of the patient's functional status and social situation and the identification of co-morbidities. The CGA enables the detection of "frailty" using screening tools assessing cognitive function, risk of falls, nutritional status, mood disorders, autonomy and social environment. The objectives of AF treatment in the elderly are to prevent AF complications, particularly stroke, and improve quality of life. Specific precautions for treatment must be taken because of the co-morbidities and age-related changes in pharmacokinetics or pharmacodynamics. Preventing AF complications relies mainly on anticoagulant therapy. Anticoagulants are recommended in patients with AF aged 75 years or above after assessing the bleeding risk using the HEMORR2HAGES or HAS-BLED scores. Novel oral anticoagulants (NOACs) are promising treatments, especially due to a lower risk of intracerebral haemorrhage. However, their prescriptions should take into account renal function (creatinine clearance assessed with Cockcroft formula) and cognitive function (for adherence to treatment). Studies including frail patients in "real life" are necessary to evaluate tolerance of NOACs. Management of AF also involves the treatment of underlying cardiomyopathy and heart rate control rather than a rhythm-control strategy as first-line therapy for elderly patients, especially if they are paucisymptomatic. Antiarrhythmic drugs should be used carefully in elderly patients because of the frequency of metabolic abnormalities and higher risk of drug interactions and bradycardia. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Stroke prevention in atrial fibrillation patients in Poland and other European countries: insights from the GARFIELD-AF registry.

PubMed

Stępińska, Janina; Kremis, Elżbieta; Konopka, Anna; Wożakowska-Kapłon, Beata; Ruszkowski, Piotr; Kukla, Piotr; Kayani, Gloria

2016-01-01

Atrial fibrillation (AF) is the most common clinically-significant arrhythmia in the adult population, and it is a strong independent risk factor for cerebrovascular accidents. Patients with non-valvular AF are five times more likely to suffer a stroke. Despite the clear recommendations for anticoagulant therapy, many clinicians are still reluctant to provide routine oral anticoagulation to patients with AF, despite the potential clinical benefits. To compare Polish and European populations of patients with AF and the every-day practice of stroke prevention in Poland and in the rest of Europe. We analysed the baseline data from the two first cohorts of patients enrolled in the GARFIELD-AF registry (an ongoing prospective, multicentre, international registry of patients newly diagnosed with AF) in Poland and in the rest of Europe. Polish AF patients are generally younger (median age 67 years in both cohorts vs. 73 in cohort 1 in the rest of Europe and 72 in cohort 2), but they carry a burden of more concomitant diseases. There are some noticeable differences in stroke prevention between Poland and the rest of Europe. The use of vitamin K antagonists (VKAs) is generally higher in other European countries in both cohorts (in Poland 41.7% in cohort 1 and 36.9% in cohort 2 vs. 55.5% in cohort 1 and 41.9% in cohort 2 in the rest of Europe). Meanwhile, it is generally more common in Poland to treat patients with both VKAs and antiplatelets (in cohort 1 20.4% of patients in Poland received vs. 12.0% in the rest of Europe). A total of 5.6% of patients in cohort 1 in Poland receive no antithrombotic treatment (it means: no VKA, oral factor Xa or thrombin inhibitors, antiplatelets), meanwhile in other countries it amounts to 8.5%. The usage of non-vitamin K oral anticoagulants is growing in Poland similarly to the other European countries. The GARFIELD-AF registry data shows how distant everyday clinical practice is from the guidelines. It shows that still in Poland, as well as in the rest of Europe, too many patients with low stroke risk are treated with anticoagulants, while too frequently patients at high stroke risk are left with no stroke prevention. Although the tendency to use non-vitamin K oral anticoagulants is growing comparably in Poland and in the rest of Europe, the proportion of patients with intermediate and high stroke risk is not growing and more patients at low stroke risk are treated with anticoagulants.

International normalized ratio stabilization in newly initiated warfarin patients with nonvalvular atrial fibrillation.

PubMed

Nelson, Winnie W; Desai, Sunita; Damaraju, C V; Lu, Lang; Fields, Larry E; Wildgoose, Peter; Schein, Jeff R

2014-12-01

Warfarin is effective for stroke prevention in patients with atrial fibrillation (AF), but international normalized ratio (INR) levels fluctuate and frequent monitoring is necessary. This study used data from a large anticoagulation management service database to analyze the relationship between INR stabilization and warfarin utilization for >1 year in patients with nonvalvular AF (NVAF). Anticoagulation records from a large US electronic database collected from 2006 to 2010 were analyzed. Patients with NVAF and ≥ 3 INR values in the dataset were identified (n = 15,276). INR stabilization was defined as the first three consecutive INR values between 2.0 and 3.0 after warfarin initiation. One quarter of patients (n = 3809) failed to reach INR stabilization. After initial stabilization, 30% of subsequent INR values were out of range. The mean (± standard deviation [SD]) follow-up time from stabilization to the end of study for these patients was 494.2 ± 418.1 days. Age ≥ 75 years (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.08-1.27), hypertension (OR = 1.19, 95% CI = 1.10-1.29), or prior stroke (OR = 1.29, 95% CI = 1.04-1.61) were positively associated with achieving stabilization; heart failure was negatively associated with stabilization (OR = 0.78, 95% CI = 0.70-0.87). Male gender (p < 0.0001) and hypertension were associated with earlier stabilization (p = 0.0013); heart failure was associated with later stabilization (p = 0.0098). Patients who achieved INR stabilization within 1 year were 10 times more likely to remain on warfarin than patients who did not achieve it. Observational data may contain incomplete records. Data on adherence, concurrent medications, vitamin K intake, genotype, reasons for discontinuation of monitoring, and patient outcomes were not available in the dataset. The study findings were generalizable only to patients with AF who were managed by anticoagulation clinics. Given the importance of stroke prevention among patients with AF, the potential for unpredictable INR patterns should be carefully considered during clinical decision-making.

Disease management: atrial fibrillation and home monitoring.

PubMed

Ricci, Renato Pietro

2013-06-01

Device-detected atrial fibrillation (AF) episodes predict poor clinical outcome regardless of symptoms. Potential benefits of remote monitoring are early arrhythmia detection and patient continuous monitoring. Several studies of device remote monitoring consistently demonstrated that AF represents the most common clinical alert and that detailed information on arrhythmia onset, duration, and burden as well as on the ventricular rate may be early available for clinical evaluation. Reaction time to AF alerts was very short in all series involving either pacemakers or defibrillators and action ability of AF alerts was very high. In the Home Guide Registry, in which 1650 patients were enrolled, AF was detected in 16.3% of patients and represented 36% of all cardiovascular events during the follow-up. Timely anticoagulation introduction in asymptomatic patients may impact on the stroke rate. According to the results of repeated Monte Carlo simulations based on a real population of 166 patients, daily monitoring may reduce the 2-year stroke risk by 9-18% with an absolute reduction of 0.2-0.6%, compared with conventional inter-visit intervals of 6-12 months. In the COMPAS trial, the incidence of hospitalizations for atrial arrhythmias and related stroke was significantly higher in the control group than in the remote monitoring group. Major questions will be addressed by the ongoing IMPACT trial in which a remote monitoring guided anticoagulation strategy based on AF detection will be compared with a physician-directed standard strategy. In patients with heart failure, AF early detection combined with other indexes may help prevent hospitalizations.

All-Cause, Stroke/Systemic Embolism-, and Major Bleeding-Related Health-Care Costs Among Elderly Patients With Nonvalvular Atrial Fibrillation Treated With Oral Anticoagulants.

PubMed

Deitelzweig, Steve; Luo, Xuemei; Gupta, Kiran; Trocio, Jeffrey; Mardekian, Jack; Curtice, Tammy; Hlavacek, Patrick; Lingohr-Smith, Melissa; Menges, Brandy; Lin, Jay

2018-05-01

In this study, all-cause, stroke/systemic embolism (SE)-related, and major bleeding (MB)-related health-care costs among elderly patients with nonvalvular atrial fibrillation (NVAF) initiating treatment with different oral anticoagulants (OACs) were compared. Patients ≥65 years of age initiating OACs, including apixaban, rivaroxaban, dabigatran, and warfarin, were identified from the Humana Research Database between January 1, 2013, and September 30, 2015. Propensity score matching was used to separately match the different OAC cohorts with the apixaban cohort. All-cause health-care costs and stroke/SE-related and MB-related medical costs per patient per month (PPPM) were compared using generalized linear or 2-part regression models. Compared to apixaban, rivaroxaban was associated with significantly higher all-cause health-care costs (US$2234 vs US$1846 PPPM, P < .001) and MB-related medical costs (US$106 vs US$47 PPPM, P < .001), dabigatran was associated with significantly higher all-cause health-care costs (US$1980 vs US$1801 PPPM, P = .007), and warfarin was associated with significantly higher all-cause health-care costs (US$2386 vs US$1929 PPPM, P < .001), stroke/SE-related medical costs (US$42 vs US$18 PPPM, P < .001), and MB-related medical costs (US$132 vs US$51 PPPM, P < .001). Among elderly patients with NVAF, other OACs were associated with higher all-cause health-care costs than apixaban.

Values and preferences for oral antithrombotic therapy in patients with atrial fibrillation: physician and patient perspectives.

PubMed

Alonso-Coello, Pablo; Montori, Victor M; Díaz, M Gloria; Devereaux, Philip J; Mas, Gemma; Diez, Ana I; Solà, Ivan; Roura, Mercè; Souto, Juan C; Oliver, Sven; Ruiz, Rafael; Coll-Vinent, Blanca; Gich, Ignasi; Schünemann, Holger J; Guyatt, Gordon

2015-12-01

Exploration of values and preferences in the context of anticoagulation therapy for atrial fibrillation (AF) remains limited. To better characterize the distribution of patient and physician values and preferences relevant to decisions regarding anticoagulation in patients with AF, we conducted interviews with patients at risk of developing AF and physicians who manage patients with AF. We interviewed 96 outpatients and 96 physicians in a multicenter study and elicited the maximal increased risk of bleeding (threshold risk) that respondents would tolerate with warfarin vs. aspirin to achieve a reduction in three strokes in 100 patients over a 2-year period. We used the probabilistic version of the threshold technique. The median threshold risk for both patients and physicians was 10 additional bleeds (10 P = 0.7). In both groups, we observed large variability in the threshold number of bleeds, with wider variability in patients than clinicians [patient range: 0-100, physician range: 0-50]. We observed one cluster of patients and physicians who would tolerate <10 bleeds and another cluster of patients, but not physicians, who would accept more than 35. Our findings suggest wide variability in patient and physician values and preferences regarding the trade-off between strokes and bleeds. Results suggest that in individual decision making, physician and patient values and preferences will often be discordant; this mandates tailoring treatment to the individual patient's preferences. © 2014 John Wiley & Sons Ltd.

Evaluating the implementation of a quality improvement process in General Practice using a realist evaluation framework.

PubMed

Moule, Pam; Clompus, Susan; Fieldhouse, Jon; Ellis-Jones, Julie; Barker, Jacqueline

2018-05-25

Underuse of anticoagulants in atrial fibrillation is known to increase the risk of stroke and is an international problem. The National Institute for Health Care and Excellence guidance CG180 seeks to reduce atrial fibrillation related strokes through prescriptions of Non-vitamin K antagonist Oral Anticoagulants. A quality improvement programme was established by the West of England Academic Health Science Network (West of England AHSN) to implement this guidance into General Practice. A realist evaluation identified whether the quality improvement programme worked, determining how and in what circumstances. Six General Practices in 1 region, became the case study sites. Quality improvement team, doctor, and pharmacist meetings within each of the General Practices were recorded at 3 stages: initial planning, review, and final. Additionally, 15 interviews conducted with the practice leads explored experiences of the quality improvement process. Observation and interview data were analysed and compared against the initial programme theory. The quality improvement resources available were used variably, with the training being valued by all. The initial programme theories were refined. In particular, local workload pressures and individual General Practitioner experiences and pre-conceived ideas were acknowledged. Where key motivators were in place, such as prior experience, the programme achieved optimal outcomes and secured a lasting quality improvement legacy. The employment of a quality improvement programme can deliver practice change and improvement legacy outcomes when particular mechanisms are employed and in contexts where there is a commitment to improve service. © 2018 John Wiley & Sons, Ltd.

Characteristics of Apixaban-Treated Patients, Evaluation of the Dose Prescribed, and the Persistence of Treatment: A Cohort Study in Catalonia.

PubMed

Gomez-Lumbreras, Ainhoa; Cortes, Jordi; Giner-Soriano, Maria; Quijada-Manuitt, M Angeles; Morros, Rosa

2018-01-01

Apixaban is a direct oral anticoagulant, which inhibits factor Xa. It has demonstrated clinical efficacy in prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation and a better safety profile compared to warfarin. (1) To describe the characteristics of patients with nonvalvular atrial fibrillation beginning treatment with apixaban, (2) to analyze concomitant prescriptions of medications that could potentially interact with apixaban, (3) to evaluate the level of appropriate usage according to the recommended dosage, and (4) to estimate the level of apixaban persistence among naive and non-naive patients. Cohort study using data from primary care (System for Research in Primary Care database, users of the Institut Català de la Salut; Catalonia, Spain) from August 2013 to December 2015. Mean age for apixaban-treated patients was 71.8 years (standard deviation = 11.1) and 55.6% were male. In all, 3.2% of patients receiving apixaban were taking drugs described as potentially related to either pharmacokinetic or pharmacodynamic interactions. According to the summary of product characteristics, 81.1% of patients with a recommended dose of 2.5 mg twice daily and 51.8% with a recommended dose of 5 mg twice daily actually took this dose. After 1 year of follow-up, 62.6% of the apixaban users showed good adherence. The prescribed dose of apixaban did not fully follow the recommended dose, particularly in patients who were treatment naive. Patients with a prior history of anticoagulant treatment were more likely to remain persistent to treatment with apixaban.

Clinical Relevance of Anticoagulation and Dual Antiplatelet Therapy to the Outcomes of Patients With Atrial Fibrillation and Recent Percutaneous Coronary Intervention With Stent.

PubMed

De Vecchis, Renato; Cantatrione, Claudio; Mazzei, Damiana

2016-02-01

Chronic atrial fibrillation (AF), coexisting with a history of recent coronary angioplasty with stent (PCI-S), represents an encoded indication for oral anticoagulation (OAC) with warfarin plus dual antiplatelet therapy (DAPT). Using a retrospective cohort study, we determined the respective impacts on cardiovascular outcomes of three different pharmacologic regimens, i.e., triple therapy (TT) with warfarin + clopidogrel and aspirin, dual therapy (DT) with warfarin + clopidogrel or aspirin, and DAPT with clopidogrel + aspirin. Outcomes of interest were all-cause mortality, ischemic cardiac events, ischemic cerebral events, and bleeding events. The inclusion criterion was the coexistence of an indication for OAC (e.g., chronic AF) with an indication for DAPT due to recent PCI-S. Among the 98 patients enrolled, 48 (49%), 31 (31.6%), and 19 (19.4%) patients were prescribed TT, DT, and DAPT, respectively. Throughout a mean follow-up of 378 ± 15.7 days, there were no significant differences between the three regimens for all abovementioned outcomes. In particular, the total frequency of major bleeding was similar in the three groups: five cases (10.4%) in TT, one case (3.22%) in DT and no case in DAPT groups (Chi-square test, P = 0.1987). TT, DT and DAPT displayed similar efficacy and safety. Although the superiority of OAC vs. DAPT for stroke prevention in AF patients has been demonstrated by previous randomized trials, a smaller frequency of high thromboembolic risks' features in DAPT group of the present study may have prevented the observation of a higher incidence of ischemic stroke in this group.

A Novel Carotid Device for Embolic Diversion: Lessons Learned from a 'First in Man' Trial in Patients with Atrial Fibrillation

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

Sievert, Horst, E-mail: info@cvcfrankfurt.de; Franke, Jennifer; Grad, Ygael

Purpose: This study was designed to investigate a novel device that was developed to direct emboli away from the internal carotid artery to the external carotid artery to prevent embolic stroke while avoiding the necessity for anticoagulation with warfarin. Methods: A stent-like, self-expandable filter was developed consisting of fine cobalt alloy mesh. After promising preclinical animal testing, the device was implanted into the common carotid artery extending into the external carotid artery in three patients with atrial fibrillation, each of whom were at high-risk for cerebral emboli and were suboptimal candidates for anticoagulation. Follow-up was performed clinically and with carotidmore » duplex ultrasound. Results: The implantation was successful in all three patients. Unrestricted flow through the filter was demonstrated in each patient at 6 months by duplex sonography. However, at 7 months ultrasound demonstrated occlusion of the internal carotid artery filter in one patient, which was subsequently confirmed by angiography. Subtotal filter occlusion occurred in a second patient at 14 months. Neither patient had clinical symptoms. Both internal carotid arteries were successfully recanalized using standard angioplasty techniques without complication. The third patient had completely normal carotid blood flow at 29 months follow-up. Conclusions: Implantation of a novel device intended to divert emboli away from the internal carotid artery was feasible, but resulted in occlusive neointimal proliferation in two of three patients. These results demonstrate a discrepancy from the findings of preclinical animal studies and human investigation.« less

[Recent and upcoming randomized trials for left atrial appendage occlusion : Need for a definite assessment of the situation].

PubMed

Skurk, Carsten; Hartung, Johannes Jakob; Landmesser, Ulf

2017-12-01

Atrial fibrillation (AF) is the most common arrhythmia affecting more than 1.6 million patients in Germany. Based on demographic developments, an the number is expected to increase. Embolic strokes in AF patients are particularly severe, and individualized new oral anticoagulant (NOAC) therapy reduces the incidence of stroke in these patients by approximately 70%. Besides vitamin K antagonists, the NOACs rivaroxaban, dabigatran, apixaban, and edoxaban have been introduced into clinical practice; however, major bleeding still occurs at a rate of 2-3% per year. Moreover, randomized studies and real-life registries suggest that >20% of patients with AF and an indication for anticoagulation cannot tolerate chronic oral anticoagulant therapy. Therefore, an alternative method for stroke prevention in AF patients has been developed, i. e., catheter-based exclusion of the left atrial appendage (LAA), a location that is prone for thrombus formation in these patients. The randomized trials of catheter-based LAA occlusion have compared this interventional therapy with vitamin K antagonists. In the future, however, LAA exclusion needs to be compared with NOAC therapy. Moreover, percutaneous LAA exclusion in clinical practice is mostly offered to patients ineligible for long-term oral anticoagulation or with high bleeding risk. However, no controlled, randomized trial data exist for this patient population. These data are needed for appropriate clinical judgment and optimal clinical management. Ongoing studies and scientific questions that are important to define the future for catheter-based LAA closure are discussed in this review.

Factors associated with confidence in decision making and satisfaction with risk communication among patients with atrial fibrillation.

PubMed

Hedberg, Berith; Malm, Dan; Karlsson, Jan-Erik; Årestedt, Kristofer; Broström, Anders

2018-06-01

Atrial fibrillation is a prevalent cardiac arrhythmia. Effective communication of risks (e.g. stroke risk) and benefits of treatment (e.g. oral anticoagulants) is crucial for the process of shared decision making. The aim of this study was to explore factors associated with confidence in decision making and satisfaction with risk communication after a follow-up visit among patients who three months earlier had visited an emergency room for atrial fibrillation related symptoms. A cross-sectional design was used and 322 patients (34% women), mean age 66.1 years (SD 10.5 years) with atrial fibrillation were included in the south of Sweden. Clinical examinations were done post an atrial fibrillation episode. Self-rating scales for communication (Combined Outcome Measure for Risk Communication and Treatment Decision Making Effectiveness), uncertainty in illness (Mishel Uncertainty in Illness Scale-Community), mastery of daily life (Mastery Scale), depressive symptoms (Hospital Anxiety and Depression Scale) and vitality, physical health and mental health (36-item Short Form Health Survey) were used to collect data. Decreased vitality and mastery of daily life, as well as increased uncertainty in illness, were independently associated with lower confidence in decision making. Absence of hypertension and increased uncertainty in illness were independently associated with lower satisfaction with risk communication. Clinical atrial fibrillation variables or depressive symptoms were not associated with satisfaction with confidence in decision making or satisfaction with risk communication. The final models explained 29.1% and 29.5% of the variance in confidence in decision making and satisfaction with risk communication. Confidence in decision making is associated with decreased vitality and mastery of daily life, as well as increased uncertainty in illness, while absence of hypertension and increased uncertainty in illness are associated with risk communication satisfaction.

Apixaban for periprocedural anticoagulation during catheter ablation of atrial fibrillation: a systematic review and meta-analysis of 1691 patients.

PubMed

Blandino, Alessandro; Bianchi, Francesca; Biondi-Zoccai, Giuseppe; Grossi, Stefano; Conte, Maria Rosa; Rametta, Francesco; Gaita, Fiorenzo

2016-09-01

Apixaban, a direct factor Xa inhibitor recently approved for thromboembolic prophylaxis in patients with nonvalvular atrial fibrillation (AF), is increasingly used in patients undergoing catheter ablation of AF. However, large randomized studies supporting its use in the ablation context are still lacking. We undertook the present meta-analysis to assess the impact of apixaban in terms of thromboembolic and bleeding events in patients undergoing AF ablation as compared to warfarin. MEDLINE/PubMed, Cochrane Library, and references reporting AF ablation and apixaban were screened and studies included if matching inclusion and exclusion criteria. One randomized and five nonrandomized studies were included in the analysis. Patients enrolled were 1691 patients (668 on apixaban and 1023 on warfarin). There was no heterogeneity in all the outcome comparisons. No deaths were reported. We did not observe any difference between apixaban and warfarin with respect to thromboembolic events (OR = 1.10, 95 % CI 0.24-5.16), major bleedings (OR = 1.56, 95 % CI 0.59-4.13), cardiac tamponade (OR 1.69, 95 % CI 0.52-5.54), minor bleedings (OR 0.96, 95 % CI 0.58-1.59), and the composite endpoint of death, thromboembolic events, and bleedings (OR 1.03, 95 % CI 0.65-1.64). The rates of death, thromboembolic events, major bleedings including cardiac tamponade, and minor bleedings in patients on apixaban undergoing AF ablation are very low and similar to that seen in patients treated with uninterrupted warfarin. Although primary driven by nonrandomized studies, these results support apixaban as periprocedural anticoagulation during AF ablation procedures.

Incidence and characteristics of major bleeding among rivaroxaban users with renal disease and nonvalvular atrial fibrillation

PubMed Central

Patel, Manesh R.; Peacock, W. Frank; Tamayo, Sally; Sicignano, Nicholas; Hopf, Kathleen P.; Yuan, Zhong

2018-01-01

Objective Patients with nonvalvular atrial fibrillation (AF) and renal disease (RD) who receive anticoagulation therapy appear to be at greater risk of major bleeding (MB) than AF patients without RD. As observed in past studies, anticoagulants are frequently withheld from AF patients with RD due to concerns regarding bleeding. The objective of this study was to evaluate the incidence and pattern of MB in those with RD, as compared to those without RD, in a population of rivaroxaban users with nonvalvular AF. Methods Electronic medical records of over 10 million patients from the Department of Defense Military Health System were queried to identify rivaroxaban users with nonvalvular AF. A validated algorithm was used to identify MB-related hospitalizations. RD was defined through diagnostic codes present within 6 months prior to the bleeding date for MB cases and end of study participation for non-MB patients. Data were collected on patient characteristics, comorbidities, MB management, and outcomes. Results Overall, 44,793 rivaroxaban users with nonvalvular AF were identified. RD was present among 6,921 patients (15.5%). Patients with RD had a higher rate of MB than those without RD, 4.52 per 100 person-years versus 2.54 per 100 person-years, respectively. The fatal bleeding outcome rate (0.09 per 100 person-years) was identical between those with and without RD. Conclusion In this post-marketing study of 44,793 rivaroxaban users with nonvalvular AF, RD patients experienced a higher MB rate than those without RD. The higher rate of MB among those with RD may be due to the confounding effects of comorbidities. PMID:29618192

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.

Gender differences in clinical presentation and 1-year outcomes in atrial fibrillation

PubMed Central

Schnabel, Renate B; Pecen, Ladislav; Ojeda, Francisco M; Lucerna, Markus; Rzayeva, Nargiz; Blankenberg, Stefan; Darius, Harald; Kotecha, Dipak; Caterina, Raffaele De; Kirchhof, Paulus

2017-01-01

Objectives Our objective was to examine gender differences in clinical presentation, management and prognosis of atrial fibrillation (AF) in a contemporary cohort. Methods In 6412 patients, 39.7% women, of the PREvention oF thromboembolic events – European Registry in Atrial Fibrillation, we examined gender differences in symptoms, risk factors, therapies and 1-year incidence of adverse outcomes. Results Men with AF were on average younger than women (mean±SD: 70.1±10.7 vs 74.1±9.7 years, p<0.0001). Women more frequently had at least one AF-related symptom at least occasionally compared with men (95.4% in women, 89.8% in men, p<0.0001). Prescription of oral anticoagulation was similar, with an increase of non-vitamin K antagonist oral anticoagulants from 5.9% to 12.6% in women and from 6.2% to 12.6% in men, p<0.0001 for both. Men were more frequently treated with electrical cardioversion and ablation (20.6% and 6.3%, respectively) than women (14.9% and 3.3%, respectively), p<0.0001. Women had 65% (OR: 0.35; 95% CI (0.22 to 0.56)) lower age-adjusted and country-adjusted odds of coronary revascularisation, 40% (OR: 0.60; (0.38 to 0.93)) lower odds of acute coronary syndrome and 20% (OR: 0.80; (0.68 to 0.96)) lower odds of heart failure at 1 year. There were no statistically significant gender differences in 1-year stroke/transient ischaemic attack/arterial thromboembolism and major bleeding events. Conclusion In a ‘real-world’ European AF registry, women were more symptomatic but less likely to receive invasive rhythm control therapy such as electrical cardioversion or ablation. Further study is needed to confirm that these differences do not disadvantage women with AF. PMID:28228467

Novel factor Xa inhibitors: a patent review.

PubMed

de Candia, Modesto; Lopopolo, Gianfranco; Altomare, Cosimo

2009-11-01

New oral anticoagulants with favorable safety profiles and fixed doses are required for the management of thromboembolism and stroke prevention in patients with atrial fibrillation. Among them, fXa inhibitors (the so-called xabans) are attractive options that can overcome limitations (e.g., bleeding) of the current oral antithrombotic therapy. The rational design of small-molecule direct fXa inhibitors, whose importance is testified by the growing number of publications and patents recently registered, has been fully supported by the X-ray crystallography of enzyme-ligand complexes. Pubmed, SciFinder Scholar, ISI web of knowledge(SM), http://ep.espacenet.com/ and Google websites were used as the main sources for literature retrieving, and > 100 patents filed between 2006 and April 2009, reviewed and discussed herein, highlight the variety among the P1 and P4 moieties on suitable scaffolds. The replacement of the benzamidine P1 moiety, which characterizes the first generation, with less basic bioisosteric or nonpolar neutral P1 groups led to the disclosure of numerous fXa inhibitors with high potency, selectivity and oral bioavailability. Novel selective fXa inhibitors with stable pharmacokinetics, better therapeutic windows and ease-of-use than the existing anticoagulants are currently under advanced stage clinical trials. Available data from Phase II and Phase III studies reflect the drive towards fXa inhibitors as potentially more effective and safer antithrombotic drugs. Their development is expected to address two major needs for anticoagulation, namely safety and ease-of-use, and to significantly affect the anticoagulant market.

Rationale, design, and preliminary results of the Quebec Warfarin Cohort Study.

PubMed

Perreault, Sylvie; Shahabi, Payman; Côté, Robert; Dumas, Stéphanie; Rouleau-Mailloux, Étienne; Feroz Zada, Yassamin; Provost, Sylvie; Mongrain, Ian; Dorais, Marc; Huynh, Thao; Kouz, Simon; Diaz, Ariel; Blostein, Mark; de Denus, Simon; Turgeon, Jacques; Ginsberg, Jeffrey; Lelorier, Jacques; Lalonde, Lyne; Busque, Lambert; Kassis, Jeannine; Talajic, Mario; Tardif, Jean-Claude; Dubé, Marie-Pierre

2018-05-01

Over- and undercoagulation with warfarin are associated with hemorrhagic and thromboembolic events, respectively. Genetic and clinical factors affect warfarin response, and the causes of this variability remain unclear. We present descriptive statistics and test for predictors of poor anticoagulation control. The Quebec Warfarin Cohort (QWC) comprises 1059 new warfarin users, with prospective follow-up using telephone questionnaires every 3 months for 1 year, and using healthcare administrative databases (RAMQ and Med-Echo) for 5 years prior to cohort entry and up to 10 years following active patient participation. Genetic material was collected, and genotyping of CYP2C9 and VKORC1 genes was conducted. Measured outcomes included the percentage of time patients spent within therapeutic range, anticoagulation control, warfarin dose, bleeding, and thromboembolic events. We report baseline characteristics and outcomes after 1 year of follow-up. Poor anticoagulation control was defined as time in therapeutic range <60% in the 3- to 12-month interval. Participants had a mean age of 71 years, and 62% were men. The most common indication for warfarin was atrial fibrillation (87%). Mean time in therapeutic range was 56% (±25%) in the 3 months following warfarin initiation, and 70% (±21%) in the 3- to 12-month interval. During follow-up, the rate of stroke or systemic embolism was 1.8 events per 100 person-years; for major bleeding events, 3.3 events per 100 person-years. Independent predictors of poor anticoagulation control were chronic kidney disease, heart failure, dyslipidemia, and age. The QWC represents a good research cohort to investigate clinical and genetic factors in a warfarin-anticoagulated population. © 2018 Wiley Periodicals, Inc.

Managing the therapeutic dilemma: patients with spontaneous intracerebral hemorrhage and urgent need for anticoagulation.

PubMed

Bertram, M; Bonsanto, M; Hacke, W; Schwab, S

2000-03-01

Physicians face a therapeutic dilemma in patients with acute hemorrhagic stroke requiring long-term, high-intensity anticoagulants because this treatment increases the risk of intracranial hemorrhage (ICH) 8- to 11-fold. We retrospectively studied 15 patients with ICH which occurred under anticoagulation with phenprocoumon, with an international norrmalized ratio (INR) of 2.5-6.5 on admission. Hemispheric, thalamic, cerebellar, intraventricular, or subarachnoid hemorrhage without aneurysm occurred. Absolute indications for anticoagulation were double, mitral, or aortic valve replacement, combined mitral valve failure with atrial fibrillation and atrial enlargement, internal carotid artery-jugular vein graft, frequently recurring deep vein thrombosis with risk of pulmonary embolism, and severe nontreatable ischemic heart disease. As soon as the diagnosis of ICH was established, INR normalization was attempted in all patients by administration of prothrombin complex, fresh frozen plasma, or vitamin K. After giving phenprocoumon antagonists (and neurosurgical therapy in four patients) heparin administration was started. Nine patients received full-dose intravenous and six low-dose subcutaneous heparin. The following observations were made: (a) All patients with effective, full-dose heparin treatment with a 1.5- to 2-fold elevation in partial thromboplastin time after normalization of the INR were discharged without complication. (b) Three of four of the patients with only incomplete correction of the INR (> 1.35) experienced relevant rebleeding within 3 days (all patients with an INR higher than 1.5), two of whom were on full-dose heparin. (c) Three of seven of the patients with normalized INR and without significant PTT elevation developed severe cerebral embolism. Although our data are based on a retrospective analysis, they support treatment with intravenous heparin (partial thromboplastin time 1.5-2 times baseline value) after normalization of the INR in patients with an ICH and an urgent need for anticoagulation.

Comparative effectiveness of dabigatran and rivaroxaban versus warfarin for the treatment of non-valvular atrial fibrillation

PubMed Central

Bengtson, Lindsay GS; Lutsey, Pamela L.; Chen, Lin Y.; MacLehose, Richard F.; Alonso, Alvaro

2016-01-01

Background Effectiveness data on novel oral anticoagulants (NOACs) versus warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) by prior warfarin use are limited. Methods We used data from the US MarketScan databases from 2009–2012. NVAF patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users. Propensity score-adjusted Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) for relevant endpoints in NOACs versus warfarin users. Separate analyses were conducted to compare anticoagulant-naïve users of NOACs and those switching from warfarin. Results Among 32,918 dabigatran, 3,301 rivaroxaban, and 109,447 warfarin users with NVAF, 225 intracranial bleeds, 1035 ischemic strokes, 958 myocardial infarctions, and 1842 gastrointestinal bleeds were identified. Compared to warfarin users, patients initiating NOACs had similar ischemic stroke rates and lower intracranial bleeding rates, while the gastrointestinal bleeding rate was higher in dabigatran users than warfarin users. Associations of dabigatran with ischemic stroke risk differed between anticoagulant-naïve initiators and patients switching from warfarin; dabigatran was associated with lower ischemic stroke rates in naïve users (HR 0.65, 95%CI 0.52–0.82) but not in switchers (HR 1.20, 95%CI 0.95–1.51), compared to warfarin. Risk of stroke and bleeding was not different between rivaroxaban and warfarin users. Conclusions Real-world effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in published clinical trials. However, harms and benefits of switching from warfarin to dabigatran need to be evaluated. PMID:27889397

Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for atrial fibrillation in Portugal.

PubMed

Costa, João; Fiorentino, Francesca; Caldeira, Daniel; Inês, Mónica; Lopes Pereira, Catarina; Pinheiro, Luís; Vaz-Carneiro, António; Borges, Margarida; Gouveia, Miguel

2015-12-01

Recently, three novel non-vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non-valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost-effectiveness of these new oral anticoagulants in Portuguese AF patients. A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non-major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis-related groups and an expert panel. Model outputs included life years gained, quality-adjusted life years (QALYs), direct healthcare costs and incremental cost-effectiveness ratios (ICERs). Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost-effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. Apixaban is a cost-effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision-makers. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Rhythm vs. rate control of atrial fibrillation meta-analysed by number needed to treat.

PubMed

Kumana, Cyrus R; Cheung, Bernard M Y; Cheung, Giselle T Y; Ovedal, Tori; Pederson, Bjorn; Lauder, Ian J

2005-10-01

Whenever feasible, rhythm control of atrial fibrillation (AF) was generally preferred over rate control, in the belief that it offered better symptomatic relief and quality of life, and eliminated the need for anticoagulation. However, recent trials appear to challenge these assumptions. To explore the desirability of rhythm vs. rate control of AF by systematic review of pertinent, published, randomized controlled trials (RCTs) and a meta-analysis by number needed to treat (NNT) year(-1), with respect to diverse clinically important outcomes. RCTs of outcome primarily comparing rate vs. rhythm control in patients with spontaneous AF were identified. For each outcome and assuming rhythm control to be the active treatment, relative risk reduction (RRR) and NNT year(-1) were derived for individual trials together with an NNT year(-1) for all trials combined; corresponding 95% confidence intervals (CI) were also calculated. Adverse drug reaction (ADR) and quality of life reporting were also assessed. In all, data from five suitable RCTs (entailing 5239 patients) were analysed. For hospitalization, available RRRs and NNT year(-1) values were all clinically and statistically significant. Overall, one additional patient was hospitalized for every 35 assigned to rhythm control (95% CI 27, 48). For the endpoints of death, 'ischaemic' stroke and 'non-CNS' bleeding, there was no significant difference. ADRs were significantly more common in rhythm control patients, whereas quality of life assessments revealed no difference. Thromboembolism was associated with cessation of or subtherapeutic anticoagulation, irrespective of treatment assignment. Reduced risk of hospitalization and non-inferiority for other endpoints all favour rate control, the less costly strategy. If symptoms of AF are not a problem, treatment should target optimizing rate control and more widespread and effective prophylactic anticoagulation.

Safety and efficacy of switching anticoagulation to aspirin three months after successful radiofrequency catheter ablation of atrial fibrillation.

PubMed

Uhm, Jae-Sun; Won, Hoyoun; Joung, Boyoung; Nam, Gi-Byoung; Choi, Kee-Joon; Lee, Moon-Hyoung; Kim, You-Ho; Pak, Hui-Nam

2014-09-01

Although current guidelines recommend continuing the same antithrombotic strategy regardless of rhythm control after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), anticoagulation has a risk of major bleeding. We evaluated the safety of switching warfarin to aspirin in patients with successful AF ablation. Among 721 patients who underwent RFCA of AF, 608 patients (age, 57.3±10.9 years; 77.0% male, 75.5% paroxysmal AF) who had no evidence of AF recurrence at 3 months post-RFCA were included. We compared the thromboembolic and hemorrhagic events in patients for whom warfarin was switched to aspirin (ASA group; n=296) and patients who were kept on warfarin therapy (W group; n=312). There were no significant differences in CHA₂DS₂-VASc or HAS-BLED scores between the groups. In 30 patients in the ASA group and 37 patients in W group, AF recurred and warfarin was restarted or maintained during the 18.0±12.2 months of follow-up. There were no significant differences in thromboembolic (0.3% vs. 1.0%, p=0.342) and major bleeding incidences (0.7% vs. 0.6%, p=0.958) between ASA and W groups during the follow-up period. In the 259 patients with a CHA₂DS₂-VASc score≥2, there were no significant differences in thromboembolism (0.8% and 2.2%, p=0.380) or major bleeding incidences (0.8% and 1.4%, p=0.640) between ASA and W groups. Switching warfarin to aspirin 3 months after successful RFCA of AF could be as safe and efficacious as long-term anticoagulation even in patients with CHA₂DS₂-VASc score≥2. However, strict rhythm monitoring cannot be overemphasized.

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.

The Patterns of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Use in Patients with Atrial Fibrillation in Seven Balkan Countries: a Report from the BALKAN-AF Survey.

PubMed

Potpara, Tatjana S; Trendafilova, Elina; Dan, Gheorghe-Andrei; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Gjini, Viktor; Pojskic, Belma; Popescu, Mircea Ioakim; Georgescu, Catalina Arsenescu; Dimitrova, Elena S; Kamenova, Delyana; Ekmeciu, Uliks; Mrsic, Denis; Nenezic, Ana; Brusich, Sandro; Milanov, Srdjan; Zeljkovic, Ivan; Lip, Gregory Y H

2017-08-01

Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs). A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants). Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20-3.56], rhythm control (OR 1.64, 1.25-2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51-3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis. NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.

New-onset atrial fibrillation: an update.

PubMed

Omae, Takeshi; Inada, Eiichi

2018-06-01

New-onset atrial fibrillation (NOAF) is the most common perioperative complication of heart surgery, typically occurring in the perioperative period. NOAF commonly occurs in patients who are elderly, or have left atrial enlargement, or left ventricular hypertrophy. Various factors have been identified as being involved in the development of NOAF, and numerous approaches have been proposed for its prevention and treatment. Risk factors include diabetes, obesity, and metabolic syndrome. For prevention of NOAF, β-blockers and amiodarone are particularly effective and are recommended by guidelines. NOAF can be treated by rhythm/rate control, and antithrombotic therapy. Treatment is required in patients with decreased cardiac function, a heart rate exceeding 130 beats/min, or persistent NOAF lasting for ≥ 48 h. It is anticipated that anticoagulant therapies, as well as hemodynamic management, will also play a major role in the management of NOAF. When using warfarin as an anticoagulant, its dose should be adjusted based on PT-INR. PT-INR should be controlled between 2.0 and 3.0 in patients aged < 70 years and between 1.6 and 2.6 in those aged ≥ 70 years. Rate control combined with antithrombotic therapies for NOAF is expected to contribute to further advances in treatment and improvement of survival.

Gastrointestinal disorders and dabigatran.

PubMed

Hoffman, Arthur; Galle, P R

2013-01-01

Anticoagulants play an important role in the prevention and treatment of a variety of acute and chronic thromboembolic disorders such as primary prevention and treatment of venous thromboembolism or prevention of stroke and systemic embolism in atrial fibrillation just to name of few. Within recent years, a promising new oral anticoagulant, the direct thrombin inhibitor dabigatran etexilate (dabigatran) successfully underwent clinical development and has emerged as an alternative to vitamin K antagonists according to a variety of recently revised and updated international guidelines referring to the indication of stroke prevention in atrial fibrillation. Considering the intensive clinical use of vitamin K antagonists in the mentioned indication as well as the widespread and increasing therapeutic need on one hand and the likely availability of a more efficacious alternative with fewer limitations in clinical practice on the other, there is good reason to assume that the use of dabigatran may be broad within the general medical community in the near future. Based on what is currently published in the public domain and clinical trial data it is suggested that dabigatran etexilate is associated with higher rates of dyspeptic symptoms compared to warfarin. Therefore, it is the authors' intent to review and discuss this potential dyspeptic side effect profile of dabigatran and potential counter measures from a gastroenterologist's perspective.

ANMCO/AIAC/SICI-GISE/SIC/SICCH Consensus Document: percutaneous occlusion of the left atrial appendage in non-valvular atrial fibrillation patients: indications, patient selection, staff skills, organisation, and training

PubMed Central

Gulizia, Michele Massimo; Molon, Giulio; Mazzone, Patrizio; Audo, Andrea; Casolo, Giancarlo; Di Lorenzo, Emilio; Portoghese, Michele; Pristipino, Christian; Ricci, Renato Pietro; Themistoclakis, Sakis; Padeletti, Luigi; Tondo, Claudio; Berti, Sergio; Oreglia, Jacopo Andrea; Gerosa, Gino; Zanobini, Marco; Ussia, Gian Paolo; Musumeci, Giuseppe; Romeo, Francesco; Di Bartolomeo, Roberto

2017-01-01

Abstract Atrial fibrillation (AF) is the most common arrhythmia and its prevalence is increasing due to the progressive aging of the population. About 20% of strokes are attributable to AF and AF patients are at five-fold increased risk of stroke. The mainstay of treatment of AF is the prevention of thromboembolic complications with oral anticoagulation therapy. Drug treatment for many years has been based on the use of vitamin K antagonists, but recently newer and safer molecules have been introduced (dabigatran etexilate, rivaroxaban, apixaban, and edoxaban). Despite these advances, many patients still do not receive adequate anticoagulation therapy because of contraindications (relative and absolute) to this treatment. Over the last decade, percutaneous closure of left atrial appendage, main site of thrombus formation during AF, proved effective in reducing thromboembolic complications, thus offering a valid medical treatment especially in patients at increased bleeding risk. The aim of this consensus document is to review the main aspects of left atrial appendage occlusion (selection and multidisciplinary assessment of patients, currently available methods and devices, requirements for centres and operators, associated therapies and follow-up modalities) having as a ground the significant evolution of techniques and the available relevant clinical data. PMID:28751849

Importance of anticoagulation and postablation silent cerebral lesions: Subanalyses of REVOLUTION and reMARQable studies.

PubMed

Grimaldi, Massimo; Swarup, Vijay; DeVille, Brian; Sussman, Jonathan; Jaïs, Pierre; Gaita, Fiorenzo; Duytschaever, Mattias; Ng, G Andre; Daoud, Emile; Lakkireddy, Dhanunjaya Dj; Horton, Rodney; Wickliffe, Andrew; Ellis, Christopher; Geller, Laszlo

2017-12-01

Silent cerebral lesions (SCLs) are a potential complication of left atrial radiofrequency ablation (RFA) procedures for paroxysmal atrial fibrillation (PAF). We aimed to compare the incidence of SCLs in patients treated with irrigated RFA multielectrode catheters (nMARQ ® Catheter group) and irrigated focal RFA catheters (NAVISTAR ® THERMOCOOL ® Catheter; TC group) after PAF ablation from subpopulation neurological assessment (SNA) cohorts of the REVOLUTION and reMARQable studies. Data from SNA cohorts in the prospective, nonrandomized REVOLUTION study (March 2011-September 2013) and the prospective, randomized, controlled reMARQable study (October 2013-November 2015) were included. The incidence of SCLs was assessed pre- and postablation using magnetic resonance imaging. Neurological deficits were assessed using the National Institutes of Health Stroke Scale, modified Rankin Scale, and Montreal Cognitive Assessment. A total of 37 patients from REVOLUTION and 76 patients from reMARQable were included in the SNA cohort of each study. In the REVOLUTION SNA cohort, the incidence of SCLs was 21.1% (4/19) in the nMARQ ® Catheter group and 5.9% (1/17) in the TC group. Findings from REVOLUTION helped inform the reMARQable study protocol's stringent anticoagulation regimen. SCL incidence was subsequently reduced in both groups (nMARQ ® Catheter, 7.9%; TC, 3.3%). No permanent neurological deficits were observed. Adherence to a stringent anticoagulation regimen prior to and during ablation procedures appears to be an important factor in minimizing the risk of SCL. © 2017 Wiley Periodicals, Inc.

Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective: Results From the ARISTOTLE Randomized Clinical Trial.

PubMed

Cowper, Patricia A; Sheng, Shubin; Lopes, Renato D; Anstrom, Kevin J; Stafford, Judith A; Davidson-Ray, Linda; Al-Khatib, Sana M; Ansell, Jack; Dorian, Paul; Husted, Steen; McMurray, John J V; Steg, P Gabriel; Alexander, John H; Wallentin, Lars; Granger, Christopher B; Mark, Daniel B

2017-05-01

The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial. To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system. This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011. Apixaban therapy vs warfarin therapy. Within-trial resource use and cost were compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed. Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, -$60; 95% CI, -$2728 to $2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($53 925 per quality-adjusted life year, with 98% likelihood of meeting a $100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon. Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness. clinicaltrials.gov Identifier: NCT00412984.

Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective

PubMed Central

Sheng, Shubin; Lopes, Renato D.; Anstrom, Kevin J.; Stafford, Judith A.; Davidson-Ray, Linda; Al-Khatib, Sana M.; Ansell, Jack; Dorian, Paul; Husted, Steen; McMurray, John J. V.; Steg, P. Gabriel; Alexander, John H.; Wallentin, Lars; Granger, Christopher B.; Mark, Daniel B.

2017-01-01

Importance The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial. Objective To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system. Design, Setting, and Participants This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011. Interventions Apixaban therapy vs warfarin therapy. Main Outcomes and Measures Within-trial resource use and cost were compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed. Results Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, −$60; 95% CI, −$2728 to $2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($53 925 per quality-adjusted life year, with 98% likelihood of meeting a $100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon. Conclusions and Relevance Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness. Trial Registration clinicaltrials.gov Identifier: NCT00412984 PMID:28355434

Preclinical and clinical data for factor Xa and “universal” reversal agents☆,☆☆,★

PubMed Central

Milling, Truman J.; Kaatz, Scott

2017-01-01

Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoymolecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development. This review summarizes the published data to date on both drugs, which have the potential to change the management approach to patients with FXa inhibitoreassociated major hemorrhage. PMID:27697443

Preclinical and Clinical Data for Factor Xa and “Universal” Reversal Agents

PubMed Central

Milling, Truman J.; Kaatz, Scott

2017-01-01

Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoy molecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development. This review summarizes the published data to date on both drugs, which have the potential to change the management approach to patients with FXa inhibitor–associated major hemorrhage. PMID:27575436

Non-Vitamin K Oral Anticoagulants (NOACs) A Review of Clinical Management and Laboratory Issues.

PubMed

Blann, Andrew

2016-01-01

The non-vitamin K oral anticoagulants (NOACs) are set to replace vitamin K antagonists (principally warfarin), unfractionated heparin and low molecular weight heparin as the leading antithrombotic prophylaxis in several medical and surgical settings. As a group, NOACs have a better safety profile and at least an equivalent (and sometimes superior) efficacy profile than their comparator. The objective of this review is to provide the practitioner with a comprehensive, balanced and contemporary view of these drugs and their applications. More specifically, it focuses on the evidence base for their licences, use in clinical practice (such as in renal dysfunction, orthopaedic surgery, atrial fibrillation, and venous thromboembolism, and the effects of co-medications), responses to actual or perceived haemorrhage, and the role of the laboratory.

A cost-analysis model for anticoagulant treatment in the hospital setting.

PubMed

Mody, Samir H; Huynh, Lynn; Zhuo, Daisy Y; Tran, Kevin N; Lefebvre, Patrick; Bookhart, Brahim

2014-07-01

Rivaroxaban is the first oral factor Xa inhibitor approved in the US to reduce the risk of stroke and blood clots among people with non-valvular atrial fibrillation, treat deep vein thrombosis (DVT), treat pulmonary embolism (PE), reduce the risk of recurrence of DVT and PE, and prevent DVT and PE after knee or hip replacement surgery. The objective of this study was to evaluate the costs from a hospital perspective of treating patients with rivaroxaban vs other anticoagulant agents across these five populations. An economic model was developed using treatment regimens from the ROCKET-AF, EINSTEIN-DVT and PE, and RECORD1-3 randomized clinical trials. The distribution of hospital admissions used in the model across the different populations was derived from the 2010 Healthcare Cost and Utilization Project database. The model compared total costs of anticoagulant treatment, monitoring, inpatient stay, and administration for patients receiving rivaroxaban vs other anticoagulant agents. The length of inpatient stay (LOS) was determined from the literature. Across all populations, rivaroxaban was associated with an overall mean cost savings of $1520 per patient. The largest cost savings associated with rivaroxaban was observed in patients with DVT or PE ($6205 and $2742 per patient, respectively). The main driver of the cost savings resulted from the reduction in LOS associated with rivaroxaban, contributing to ∼90% of the total savings. Furthermore, the overall mean anticoagulant treatment cost was lower for rivaroxaban vs the reference groups. The distribution of patients across indications used in the model may not be generalizable to all hospitals, where practice patterns may vary, and average LOS cost may not reflect the actual reimbursements that hospitals received. From a hospital perspective, the use of rivaroxaban may be associated with cost savings when compared to other anticoagulant treatments due to lower drug cost and shorter LOS associated with rivaroxaban.

Antithrombotic therapy in anticoagulated patients with atrial fibrillation presenting with acute coronary syndromes and/or undergoing percutaneous coronary intervention/stenting.

PubMed

Wrigley, Benjamin J; Tapp, Luke D; Shantsila, Eduard; Lip, Gregory Yh

2010-07-01

The management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary inter vention/stenting cannot be done according to a regimented common protocol, and stroke and bleeding risk stratification schema should be employed to individualize treatment options. A delicate balance is needed between the prevention of thromboembolism, against recurrent cardiac ischemia or stent thrombosis, and bleeding risk. New guidance from a consensus document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association and the European Association of Percutaneous Cardiovascular Interventions on the management of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary Intervention/Stenting has sought to clarify some of the major issues and problems surrounding this practice, and will allow clinicians to make much more informed decisions when faced with treating such patients.

Atrial cardiopathy: a mechanism of cryptogenic stroke.

PubMed

Yaghi, Shadi; Kamel, Hooman; Elkind, Mitchell S V

2017-08-01

Cryptogenic stroke accounts for approximately 30% of all ischemic strokes. Recently, atrial cardiopathy diagnosed by the presence of one of its serum, imaging, or electrocardiogram biomarkers has been shown to be associated with ischemic stroke, particularly of embolic subtypes. Areas covered: This paper aims to summarize data on occult atrial fibrillation and stroke, provide an overview on mechanisms, such as inflammation and fibrosis, of stroke in atrial cardiopathy, critically review data on biomarkers of atrial cardiopathy and their association with stroke, and suggest therapeutic implications, including directions for future research. Expert commentary: Atrial cardiopathy may constitute one of the mechanisms in cryptogenic stroke, and patients with evidence of atrial cardiopathy constitute a group of patients in whom clinical trials are warranted to test anticoagulation versus antiplatelet therapy to reduce stroke recurrence risk. In addition, more studies are needed to determine the degree of overlap between these atrial cardiopathy biomarkers and which one is more useful in predicting the risk of stroke and response to anticoagulation therapy.

Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin.

PubMed

Davidson, Bruce L; Verheijen, Sara; Lensing, Anthonie W A; Gebel, Martin; Brighton, Timothy A; Lyons, Roger M; Rehm, Jeffrey; Prins, Martin H

2014-06-01

Combined anticoagulant and aspirin therapy is associated with increased bleeding risk in patients with atrial fibrillation, but the bleeding risk of combined use of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs) is poorly documented. To estimate the bleeding risk of combined anticoagulant (rivaroxaban or enoxaparin-vitamin K antagonist [VKA]) and NSAID or aspirin therapy in patients with venous thromboembolism. Prospective analysis of observational data from the EINSTEIN deep vein thrombosis and pulmonary embolism clinical trials comparing rivaroxaban with enoxaparin-VKA treatment, trials performed in hospitals and clinics in 8246 patients enrolled from 2007 to 2009. Bleeding event rates during exposure to NSAID and aspirin therapy were compared to time without exposure. Days of NSAID or aspirin use and nonuse, clinically relevant bleeding event and major bleeding event rates by patient-years, and hazard ratios. During NSAID-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 37.5 per 100 patient-years vs 16.6 per 100 patient-years during anticoagulant use only (hazard ratio [HR], 1.77 [95% CI, 1.46-2.14]). Major bleeding during NSAID-anticoagulant treatment occurred with an event rate of 6.5 per 100 patient-years, compared to 2.0 per 100 patient-years during nonuse (HR, 2.37 [95% CI, 1.51-3.75]). For aspirin-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 36.6 per 100 patient-years, compared to 16.9 per 100 patient-years during aspirin nonuse (HR, 1.70 [95% CI, 1.38-2.11]). Major bleeding in aspirin-anticoagulant-treated patients occurred with an event rate of 4.8 per 100 patient-years, compared to 2.2 per 100 patient-years during aspirin nonuse (HR, 1.50 [95% CI, 0.86-2.62]). Increases in risk for clinically relevant and major bleeding were similar for rivaroxaban and enoxaparin-VKA anticoagulation regimens. Among patients with venous thromboembolism receiving anticoagulant therapy, concomitant use of an NSAID or aspirin is associated with an increased risk of clinically relevant and major bleeding.

A meta-analysis of phase III randomized controlled trials with novel oral anticoagulants in atrial fibrillation: comparisons between direct thrombin inhibitors vs. factor Xa inhibitors and different dosing regimens.

PubMed

Providência, Rui; Grove, Erik Lerkevang; Husted, Steen; Barra, Sérgio; Boveda, Serge; Morais, João

2014-12-01

Previous studies evaluating the ability of novel oral anticoagulants (NOAC) to prevent thromboembolism in patients with non-valvular atrial fibrillation (AF) have identified differences between the efficacy and safety of the drugs tested. Whether these differences reflect differences in direct thrombin or Xa inhibition, different dosing regimens or specific aspects of each agent or trial has not yet been explored. A search was performed on MEDLINE, EMBASE and COCHRANE, and ongoing studies were tracked on clinicaltrials.gov. Phase III randomized controlled trials of direct thrombin inhibitors (DTI) and factor Xa inhibitors (FXaI) vs. warfarin in patients with AF were eligible. Data were pooled using random-effects, according to the Mantel-Haenszel model. Sensitivity analyses were performed on DTI, FXaI, once-daily and twice-daily regimens. Seven studies were pooled, including a total of 80,290 patients. Both DTI and FXaI outperformed warfarin regarding stroke or systemic embolism, intracranial bleeding, total and cardiovascular mortality. No significant differences were found between DTI and FXaI or between once-daily and twice-daily regimens. Some drugs performed worse than warfarin regarding some secondary endpoints, including: edoxaban 30 mg bid on ischaemic stroke, dabigatran on acute myocardial infarction, dabigatran 150 mg bid and rivaroxaban 20mgod on gastrointestinal bleeding. Our pooled data do not support the hypothesis of a significant class-effect of DTI or FXaI, nor the benefit of once-daily vs. twice-daily dosing in the setting of AF, reinforcing that the choice of NOAC should be adapted to the specific patient and focused on the agent itself, rather than the pharmacological class or dosing regimen.

Dabigatran Levels in Elderly Patients with Atrial Fibrillation: First Post-Marketing Experiences.

PubMed

Bolek, Tomáš; Samoš, Matej; Škorňová, Ingrid; Stančiaková, Lucia; Staško, Ján; Galajda, Peter; Kubisz, Peter; Mokáň, Marián

2018-05-08

The number of elderly individuals with non-valvular atrial fibrillation (NV-AF) requiring long-term anticoagulation is rising. The pharmacokinetics of oral anticoagulants in elderly individuals may differ from that for younger patients. The aim of this study was to assess the dabigatran levels in elderly patients with NV-AF. A pilot prospective post-marketing study in patients with NV-AF on dabigatran therapy was performed; we enrolled 21 consecutive elderly patients (aged ≥ 75 years) on a reduced dabigatran regimen (110 mg twice daily) and compared them with 13 younger (≤ 70 years) individuals on reduced dabigatran therapy due to renal impairment and with 16 younger patients on standard dabigatran therapy (150 mg twice daily). Blood samples were taken for the assessment of dabigatran trough and peak levels. Dabigatran levels were measured with the Hemoclot ® Thrombin Inhibitor Assay. There were significant differences in dabigatran trough levels when comparing elderly patients on reduced dabigatran with non-elderly patients on reduced dabigatran (99.3 ± 73.6 vs 51.6 ± 25.6 ng/mL; p < 0.01). Similarly, the detected dabigatran peak levels were significantly higher in elderly patients on reduced dabigatran compared with non-elderly patients on reduced dabigatran (173.4 ± 116.2 vs 116.1 ± 19.1 ng/mL; p < 0.01). No significant differences in dabigatran trough and peak levels were found when comparing elderly patients on reduced dabigatran with non-elderly patients on standard dabigatran therapy. This pilot study demonstrated that elderly patients on reduced dabigatran exhibit significantly higher dabigatran levels than younger individuals on a reduced regimen, and similar levels compared with younger individuals on standard dabigatran.

Dementia correlates with anticoagulation underuse in older patients with atrial fibrillation.

PubMed

Viscogliosi, Giovanni; Ettorre, Evaristo; Chiriac, Iulia Maria

2017-09-01

Stroke prevention in older atrial fibrillation (AF) patients remains a challenge. This study aimed to investigate whether a dementia diagnosis is an independent correlate of lower prescription rate of oral anticoagulant treatment (OAT) in a sample of older AF patients. Cross-sectional retrospective study. Consecutive older community-dwelling AF patients referred for a comprehensive geriatric assessment, were considered. Evaluation of physical, social and mental health, and administration of the Cumulative Illness Rating Scale (CIRS) and Barthel Index were performed. Dementia cases were ascertained by consensus of 2 experienced geriatricians. Dementia severity was assessed using the Clinical Dementia Rating scale (CDR). 316 AF patients (ages 74.7±7.0years, 55.7% women) with high stroke risk (77.5% had a CHA 2 DS 2 VASC score ≥3), low bleeding and falling risk, and no neuropsychiatric/behavioral symptoms, were included. 60.1% were prescribed with OAT. Among patients with dementia (n=86, 27.2%), 22.0% received inadequate antithrombotic prophylaxis (i.e. antiplatelet) and 38.5% no treatment. Proportion of those receiving inadequate or no prophylaxis increased at increasing CDR score. By multiple regression models, either dementia (yes vs no), OR=1.33, 95%CI=1.11-1.46, p<0.001, and dementia severity (CDR>1), OR=2.38, 95%CI=2.19-2.60, p<0.001, were associated with lack of OAT prescription independently of age, paroxysmal AF, and comorbidity burden. Dementia might be associated with underuse of OAT in older AF patients even in the absence of established contraindications. Future studies are needed to assess the real dimension of the problem and clinician's barriers to prescribing OAT in demented patients. Copyright © 2017. Published by Elsevier B.V.

Meta-analysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants.

PubMed

Pancholy, Samir B; Sharma, Parikshit S; Pancholy, Dipti S; Patel, Tejas M; Callans, David J; Marchlinski, Francis E

2014-02-01

Studies comparing gender-specific outcomes in patients with atrial fibrillation (AF) have reported conflicting results. Gender differences in cerebrovascular accident/systemic embolism (CVA/SE) or major bleeding outcomes with novel oral anticoagulant (NOAC) use are not known. The goal of this analysis was to perform a systematic review and meta-analysis evaluating gender differences in residual risk of CVA/SE and major bleeding outcomes in patients with nonvalvular AF treated with either warfarin or NOAC. Sixty-four randomized studies were identified using keywords "gender," "AF," and "CVA." Using the Preferred Reporting Items for Systemic Reviews and Meta-analysis method, 6 studies met criteria for inclusion in this meta-analysis. CVA/SE and major bleeding outcomes were separately analyzed in cohorts receiving warfarin and NOAC agents, comparing men with women. Women with AF taking warfarin were at a significantly greater residual risk of CVA/SE compared with men (odds ratio 1.279, 95% confidence interval 1.111 to 1.473, Z = -3.428, p = 0.001). No gender difference in residual risk of CVA/SE was noted in patients with AF receiving NOAC agents (odds ratio 1.146, 95% confidence interval 0.97 to 1.354, p = 0.109). Major bleeding was less frequent in women with AF treated with NOAC. In conclusion, women with AF treated with warfarin have a greater residual risk of CVA/SE and an equivalent major bleeding risk, whereas those treated with NOAC agents deemed superior to warfarin are at equivalent residual risk of CVA/SE and less major bleeding risk compared with men. These results suggest an increased net clinical benefit of NOAC agents compared with warfarin in treating women with AF. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessment of the Adherence of Cardiologists to Guidelines for the Treatment of Atrial Fibrillation

PubMed Central

van der Sand, Cézar R.; Leiria, Tiago Luiz Luz; Kalil, Renato Abdala Karam

2013-01-01

Background No local studies evaluating the knowledge of cardiologists on the management of atrial fibrillation (AF) and their adherence to these guidelines are available. Objective To evaluate the knowledge of cardiologists on the guidelines and clinical practices for the treatment of AF, correlating it to the time since medical graduation. Methods Cross-sectional study randomly including cardiologists affiliated to the Society of Cardiology of the State of Rio Grande do Sul (Sociedade de Cardiologia do Estado do Rio Grande do Sul - SOCERGS). The physicians were divided into two groups, according to time since graduation: those graduated for more (G1) or less (G2) than 25 years. Results Of the 859 SOCERGS members, 150 were interviewed, and six refused to participate in the study. G1 comprised 71 physicians, and G2, 73. Differences were observed in regard to the following variables: use of betablockers as the first-choice drug for the control of AF response in 59.2% (G1) vs 91.8% (G2) (p<0.0001); use of digoxin as the preferred drug for the control of AF response in 19.7% (G1) vs 0% (G2) (p< 0.0001); warfarin as the preferred anticoagulant in 71.8% (G1) vs 93.2% (G2) (p=0.009); application of a risk score for anticoagulation in 73.2% (G1) vs 87.7% (G2) (p=0.02). In questions regarding the knowledge about the Brazilian Society of Cardiology's guideline for AF, the overall percentage of right answers was 82.3%. Conclusion Most of the clinical measures regarding the management of AF comply with the guidelines, and the clinical practice differs according with the time since graduation. PMID:23877745

Hyperuricemia and the risk of ischemic stroke in patients with atrial fibrillation--could it refine clinical risk stratification in AF?

PubMed

Chao, Tze-Fan; Liu, Chia-Jen; Chen, Su-Jung; Wang, Kang-Ling; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Chen, Tzeng-Ji; Tsao, Hsuan-Ming; Chen, Shih-Ann

2014-01-01

Although hyperuricemia has been reported to be a risk factor of stroke, the relationship between hyperuricemia and stroke in patients with atrial fibrillation (AF) remains uncertain. The goal of the present study was to investigate whether hyperuricemia could potentially refine clinical risk stratification in AF. This study used the "National Health Insurance Research Database" in Taiwan. A total of 7601 AF patients who did not receive antiplatelet agents or oral anticoagulants were identified as the study population. Hyperuricemia was defined as having at least one episode of gout attack necessitating long-term treatment with uric acid-lowering agents. The association between hyperuricemia and ischemic stroke was analyzed. During the follow up of 3.0±2.7 years, 1116 patients (14.7%) experienced ischemic stroke with an annual rate of around 4.9%. Hyperuricemia significantly predicts stroke, with a hazard ratio (HR) of 1.280 after adjusting for CHA2DS2-VASc score and other comorbidities. Among the 376 patients with a CHA2DS2VASc score of 0, hyperuricemia can further stratify them into 2 groups with different stroke rates (7.1% versus 1.3%, p=0.020). The adjusted HR of hyperuricemia in predicting ischemic stroke diminished from 7.491 for patients with a CHA2DS2-VASc score of 0 to 1.659 for those with a score of 3, and became insignificant for patients with a score ≥4. Hyperuricemia was a significant risk factor of stroke which could potentially refine the clinical risk stratification in AF. It deserves a prospective trial to investigate whether it would change the current strategy for stroke preventions using oral anticoagulants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Italian intersociety consensus on DOAC use in internal medicine.

PubMed

Prisco, Domenico; Ageno, Walter; Becattini, Cecilia; D'Angelo, Armando; Davì, Giovanni; De Cristofaro, Raimondo; Dentali, Francesco; Di Minno, Giovanni; Falanga, Anna; Gussoni, Gualberto; Masotti, Luca; Palareti, Gualtiero; Pignatelli, Pasquale; Santi, Roberto M; Santilli, Francesca; Silingardi, Mauro; Tufano, Antonella; Violi, Francesco

2017-04-01

The direct oral anticoagulants (DOACs) are drugs used in clinical practice since 2009 for the prevention of stroke or systemic embolism in non-valvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism. The four DOACs, including the three factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and one direct thrombin inhibitor (dabigatran) provide oral anticoagulation therapy alternatives to Vitamin K antagonists (VKAs). Despite their clear advantages, the DOACs require on the part of the internist a thorough knowledge of their pharmacokinetic and pharmacodynamic characteristics to ensure their correct use, laboratory monitoring and the appropriate management of adverse events. This document represents a consensus paper on the use of DOACs by representatives of three Italian scientific societies: the Italian Society of Internal Medicine (SIMI), the Federation of the Associations of Hospital Managers (FADOI), and the Society for the Study of Haemostasis and Thrombosis (SISET). This document formulates expert opinion guidance for pragmatic managing, monitoring and reversing the anticoagulant effect of DOACs in both chronic and emergency settings. This practical guidance may help the internist to create adequate protocols for patients hospitalized ion internal medicine wards, where patients are often elderly subjects affected by poly-morbidities and renal insufficiency, and, thus, require particular attention to drug-drug interactions and peri-procedural protocols.

Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians

PubMed Central

Peacock, W. Frank; Rafique, Zubaid; Singer, Adam J.

2016-01-01

Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed. PMID:27293895

Automated Software System to Promote Anticoagulation and Reduce Stroke Risk: Cluster-Randomized Controlled Trial.

PubMed

Holt, Tim A; Dalton, Andrew; Marshall, Tom; Fay, Matthew; Qureshi, Nadeem; Kirkpatrick, Susan; Hislop, Jenny; Lasserson, Daniel; Kearley, Karen; Mollison, Jill; Yu, Ly-Mee; Hobbs, F D Richard; Fitzmaurice, David

2017-03-01

Oral anticoagulants (OAC) substantially reduce risk of stroke in atrial fibrillation, but uptake is suboptimal. Electronic health records enable automated identification of people at risk but not receiving treatment. We investigated the effectiveness of a software tool (AURAS-AF [Automated Risk Assessment for Stroke in Atrial Fibrillation]) designed to identify such individuals during routine care through a cluster-randomized trial. Screen reminders appeared each time the electronic health records of an eligible patient was accessed until a decision had been taken over OAC treatment. Where OAC was not started, clinicians were prompted to indicate a reason. Control practices continued usual care. The primary outcome was the proportion of eligible individuals receiving OAC at 6 months. Secondary outcomes included rates of cardiovascular events and reports of adverse effects of the software on clinical decision-making. Forty-seven practices were randomized. The mean proportion-prescribed OAC at 6 months was 66.3% (SD=9.3) in the intervention arm and 63.9% (9.5) in the control arm (adjusted difference 1.21% [95% confidence interval -0.72 to 3.13]). Incidence of recorded transient ischemic attack was higher in the intervention practices (median 10.0 versus 2.3 per 1000 patients with atrial fibrillation; P =0.027), but at 12 months, we found a lower incidence of both all cause stroke ( P =0.06) and hemorrhage ( P =0.054). No adverse effects of the software were reported. No significant change in OAC prescribing occurred. A greater rate of diagnosis of transient ischemic attack (possibly because of improved detection or overdiagnosis) was associated with a reduction (of borderline significance) in stroke and hemorrhage over 12 months. URL: http://www.isrctn.com. Unique Identifier: ISRCTN55722437. © 2017 American Heart Association, Inc.

Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention for Newly Diagnosed and Treatment-Naive Atrial Fibrillation Patients: An Update Using 2013–2014 Data

PubMed Central

Brown, Joshua D.; Shewale, Anand R.; Talbert, Jeffery C.

2017-01-01

BACKGROUND Few studies have assessed adherence to non-vitamin K antagonist oral anticoagulants (NOACs), especially using contemporary data now that multiple NOACs are available. OBJECTIVE To compare adherence and treatment patterns among NOACs for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). METHODS Incident and treatment-naive NVAF patients were identified during 2013–2014 from a large claims database in this retrospective cohort study. Patients were included who initiated rivaroxaban, dabigatran, or apixaban within 30 days after diagnosis. Adherence to the index medication and adherence to any oral anticoagulant was assessed using the proportion of days covered (PDC) at 3, 6, and 9 months. The number of switches and gaps in therapy were also evaluated. Analyses were stratified by stroke risk scores, and a logistic regression model was used to control for factors that may predict high adherence. RESULTS Dabigatran had lower adherence (PDC = 0.76, 0.64, 0.57) compared with rivaroxaban (PDC = 0.83, 0.73, 0.66; P < 0.001) and apixaban (PDC = 0.82, 0.72, 0.66; P < 0.001) at 3, 6, and 9 months of follow-up and twice the number of switches to either other anticoagulants or antiplatelet therapy. Adherence was higher overall as stroke risk increased, and dabigatran had consistently lower adherence compared with the other NOACs. Multivariable logistic regression predicting PDC ≥ 0.80 showed rivaroxaban users with higher odds of high adherence compared with dabigatran or rivaroxaban across all time periods. Adjusted analyses showed that increasing age and comorbid hypertension and diabetes were associated with higher adherence. CONCLUSIONS In this real-world analysis of adherence to NOACs, rivaroxaban and apixaban had favorable unadjusted adherence profiles compared with dabigatran, while rivaroxaban users had higher odds of high adherence (PDC ≥ 0.80) among the NOACs in adjusted analyses. Clinicians and managed care organizations should consider the implications of lower adherence on clinical outcomes and quality assessment. PMID:28854077

Multinational development of a questionnaire assessing patient satisfaction with anticoagulant treatment: the 'Perception of Anticoagulant Treatment Questionnaire' (PACT-Q©)

PubMed Central

Prins, Martin H; Marrel, Alexia; Carita, Paulo; Anderson, David; Bousser, Marie-Germaine; Crijns, Harry; Consoli, Silla; Arnould, Benoit

2009-01-01

Background The side effects and burden of anticoagulant treatments may contribute to poor compliance and consequently to treatment failure. A specific questionnaire is necessary to assess patients' needs and their perceptions of anticoagulant treatment. Methods A conceptual model of expectation and satisfaction with anticoagulant treatment was designed by an advisory board and used to guide patient (n = 31) and clinician (n = 17) interviews in French, US English and Dutch. Patients had either atrial fibrillation (AF), deep venous thrombosis (DVT), or pulmonary embolism (PE). Following interviews, three PACT-Q language versions were developed simultaneously and further pilot-tested by 19 patients. Linguistic validations were performed for additional language versions. Results Initial concepts were developed to cover three areas of interest: 'Treatment', 'Disease and Complications' and 'Information about disease and anticoagulant treatment'. After clinician and patient interviews, concepts were further refined into four domains and 17 concepts; test versions of the PACT-Q were then created simultaneously in three languages, each containing 27 items grouped into four domains: "Treatment Expectations" (7 items), "Convenience" (11 items), "Burden of Disease and Treatment" (2 items) and "Anticoagulant Treatment Satisfaction" (7 items). No item was deleted or added after pilot testing as patients found the PACT-Q easy to understand and appropriate in length in all languages. The PACT-Q was divided into two parts: the first part to measure the expectations and the second to measure the convenience, burden and treatment satisfaction, for evaluation prior to and after anticoagulant treatment, respectively. Eleven additional language versions were linguistically validated. Conclusion The PACT-Q has been rigorously developed and linguistically validated. It is available in 14 languages for use with thromboembolic patients, including AF, PE and DVT patients. Its validation and psychometric properties have been tested and are presented in a separate manuscript. PMID:19196486

Hemorrhagic pericardial effusion as the debut of acquired hemophilia in a chronic lymphocytic leukemia patient

PubMed Central

Bastida, José María; Cano-Mozo, María Teresa; Lopez-Cadenas, Felix; Vallejo, Victor Eduardo; Merchán, Soraya; Santos-Montón, Cecilia; González-Calle, David; Carrillo, Javier; Martín, Ana Africa; Torres-Hernández, Jose Angel; González, Marcos; Martín-Herrero, Francisco; Pabón, Pedro; González-Porras, Jose Ramon

2017-01-01

Abstract Background: Acquired hemophilia A (AHA) is a rare bleeding disease caused by autoantibodies against factor VIII. Spontaneous bleeding symptoms usually affect the skin and muscle, while pericardial effusion is an extremely rare manifestation. In the elderly, anticoagulant treatment is frequent and bleeding symptoms are usually associated with this. Clinical findings: We report a hemorrhagic pericardial effusion as the AHA debut in a patient with untreated chronic lymphocytic leukemia and anticoagulated with apixaban for atrial fibrillation and chronic arterial ischemia. The patient was treated with recombinant activated factor VII to control the active bleeding and corticosteroids and cyclophosphamide to eradicate the inhibitor. In addition, a briefly review of hematological malignancies associated to acquired hemophilia was performed. Particularities: a) anticoagulant treatment may confuse the suspicion of AHA and its diagnosis; b) hemorrhagic pericardial effusion is an extremely rare presentation; c) bypassing agents raise the risk of thromboembolism; d) hematological malignancies rarely cause AHA (<20% of cases). Conclusion: A multidisciplinary team is needed to diagnose and manage AHA effectively. The use of anticoagulants may lead to the misdiagnosis of clinical symptoms. Chronic lymphocytic leukemia is one of the main causes of hematological malignancies associated. The specific treatment of CLL is still recommended in the event of active disease. PMID:29381944

[Factors influencing activity of oral anticoagulants. Interactions with drugs and food].

PubMed

Sawicka-Powierza, Jolanta; Rogowska-Szadkowska, Dorota; Ołtarzewska, Alicja Małgorzata; Chlabicz, Sławomir

2008-05-01

Oral anticoagulants (OAC) are commonly used as a life-long therapy in prevention of systemic embolism in patients with atrial fibrillation, valvular heart disease and prosthetic hart valves and in the primary and secondary prevention of venous thromboembolism. They are also used for the prevention of thromboembolic events in patients with acute myocardial infarction and with angina pectoris, in patients with biological hart valves and after some types of orthopaedics surgery. The International Normalized Ratio (INR) is used to evaluate the efficacy of anti-coagulant therapy. The risk of thromboembolic and haemorrhagic complications increases when the INR is out of the therapeutic range. The aim of this study was to present information about the factors influencing activity of oral anticoagulants and interactions between oral anticoagulants and drugs or food. The effect of oral anticoagulants is influenced by genetic and environmental factors such as: medicines, food, diseases and pre-existing conditions. A common mutation in the gene coding for the cytochrome P450 (CYP2C9), with one or more combinations of its polymorphisms, is responsible for the reduced warfarin requirements or for the resistance to warfarin. A mutation in the factor IX is responsible for the risk of bleeding during OAC therapy without excessive prolongation of the prothrombin time (PT). Drugs, herbs and multivitamin supplements can alter the absorption, pharmacokinetics or pharmakodynamics of OAC. Nonsteroid anti-inflammatory drugs and paracetamol in combination with OAC seem to be the most dangerous because they are available without prescription and are used without medical consultation. Patients on OAC therapy are sensitive to changing dietary intake of vitamin K, which is supplied from phylloquinones in plants or from vitamin K-containing medicines. The effect of OAC can be influenced by other existing factors like: fever, diarrhoea, alcohol abuse or physical hyperactivity. Some malignancies or other diseases like cardiac insufficiency, hyperthyroidism and hypothyroidism or hepatic dysfunction may also affect OAC therapy. This treatment requires patients and doctors to be knowledgeable about factors influencing the activity of oral anticoagulants. For this reason educational programme on OAC therapy should be conducted among patients and doctors.

Practical aspects of treatment with target specific anticoagulants: initiation, payment and current market, transitions, and venous thromboembolism treatment.

PubMed

Mahan, Charles E

2015-04-01

Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.

Peri-procedural interrupted oral anticoagulation for atrial fibrillation ablation: comparison of aspirin, warfarin, dabigatran, and rivaroxaban

PubMed Central

Winkle, Roger A.; Mead, R. Hardwin; Engel, Gregory; Kong, Melissa H.; Patrawala, Rob A.

2014-01-01

Aims Atrial fibrillation ablation requires peri-procedural oral anticoagulation (OAC) to prevent thromboembolic events. There are several options for OAC. We evaluate peri-procedural AF ablation complications using a variety of peri-procedural OACs. Methods and results We examined peri-procedural OAC and groin, bleeding, and thromboembolic complications for 2334 consecutive AF ablations using open irrigated-tip radiofrequency (RF) catheters. Pre-ablation OAC was warfarin in 1113 (47.7%), dabigatran 426 (18.3%), rivaroxaban 187 (8.0%), aspirin 472 (20.2%), and none 136 (5.8%). Oral anticoagulation was always interrupted and intraprocedural anticoagulation was unfractionated heparin (activated clotting time, ACT = 237 ± 26 s). Pre- and post-OAC drugs were the same for 1591 (68.2%) and were different for 743 (31.8%). Following ablation, 693 (29.7%) were treated with dabigatran and 291 (12.5%) were treated with rivaroxaban. There were no problems changing from one OAC pre-ablation to another post-ablation. Complications included 12 (0.51%) pericardial tamponades [no differences for dabigatran (P = 0.457) or rivaroxaban (P = 0.163) compared with warfarin], 12 (0.51%) groin complications [no differences for rivaroxaban (P = 0.709) and fewer for dabigatran (P = 0.041) compared with warfarin]. Only 5 of 2334 (0.21%) required blood transfusions. There were two strokes (0.086%) and no transient ischaemic attacks (TIAs) in the first 48 h post-ablation. Three additional strokes (0.13%), and two TIAs (0.086%) occurred from 48 h to 30 days. Only one stroke had a residual deficit. Compared with warfarin, the neurologic event rate was not different for dabigatran (P = 0.684) or rivaroxaban (P = 0.612). Conclusion Using interrupted OAC, low target intraprocedural ACT, and irrigated-tip RF, the rate of peri-procedural groin, haemorrhagic, and thromboembolic complications was extremely low. There were only minimal differences between OACs. Low-risk patients may remain on aspirin/no OAC pre-ablation. There are no problems changing from one OAC pre-ablation to another post-ablation. PMID:25115168

How are patients with atrial fibrillation approached and informed about their risk profile and available therapies in Europe? Results of the European Heart Rhythm Association Survey.

PubMed

Potpara, Tatjana S; Pison, Laurent; Larsen, Torben B; Estner, Heidi; Madrid, Antonio; Blomström-Lundqvist, Carina

2015-03-01

This European Heart Rhythm (EHRA) Scientific Initiatives Committee EP Wire Survey aimed at exploring the common practices in approaching patients with atrial fibrillation (AF) and informing them about their risk profiles and available therapies in Europe. In the majority of 53 responding centres, patients were seen by cardiologists (86.8%) or arrhythmologists (64.2%). First- and follow-up visits most commonly lasted 21-30 and 11-20 min (41.5 and 69.8% of centres, respectively). In most centres (80.2%) stroke and bleeding risk had the highest priority for discussion with AF patients; 50.9% of centres had a structured patient education programme for stroke prevention. Individual patient stroke risk was assessed at every visit in 69.2% of the centres; 46.1% of centres had a hospital-based anticoagulation clinic. Information about non-vitamin K oral anticoagulants (NOACs) was communicated to all AF patients eligible for oral anticoagulation (38.5% of centres) or to warfarin-naive/unstable patients (42.3%). Only two centres (3.8%) had a structured NOAC adherence follow-up programme; in eight centres (15.4%) patients were requested to sign the statement they have been informed about the risks of non-adherence to NOAC therapy, and three centres (5.8%) had a patient education programme. Patient preferences were of the highest relevance regarding oral anticoagulation and AF ablation (64.7 and 49.0% of centres, respectively). This EP Wire Survey shows that in Europe considerable amount of time and resources are used in daily clinical practice to inform AF patients about their risk profile and available therapies. However, a diversity of strategies used across the European hospitals was noted, and further research is needed to better define optimal strategies for informing AF patients about their risk profile and treatment options. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Representativeness of the dabigatran, apixaban and rivaroxaban clinical trial populations to real-world atrial fibrillation patients in the United Kingdom: a cross-sectional analysis using the General Practice Research Database

PubMed Central

Lee, Sally; Monz, Brigitta U; Clemens, Andreas; Brueckmann, Martina; Lip, Gregory Y H

2012-01-01

Objective Three oral anticoagulants have reported study results for stroke prevention in patients with atrial fibrillation (AF) (dabigatran etexilate, rivaroxaban and apixaban); all demonstrated superiority or non-inferiority compared with warfarin (RE-LY, ARISTOTLE and ROCKET-AF). This study aimed to assess the representativeness for the real-world AF population, particularly the population eligible for anticoagulants. Design A cross-sectional database analysis. Setting Dataset derived from the General Practice Research Database (GPRD). Primary and secondary outcomes measure The proportion of real-world patients with AF who met the inclusion/exclusion criteria for RE-LY, ARISTOTLE and ROCKET-AF were compared. The results were then stratified by risk of stroke using CHADS2 and CHA2DS2-VASc. Results 83 898 patients with AF were identified in the GPRD. For the population at intermediate or high risk of stroke and eligible for anticoagulant treatment (CHA2DS2-VASc ≥1; n=78 783 (94%)), the proportion eligible for inclusion into RE-LY (dabigatran etexilate) was 68% (95% CI 67.7% to 68.3%; n=53 640), compared with 65% (95% CI 64.7% to 65.3%; n=51 163) eligible for ARISTOTLE (apixaban) and 51% (95% CI 50.7% to 51.4%; n=39 892) eligible for ROCKET-AF (rivaroxaban). Using the CHADS2 method of risk stratification, for the population at intermediate or high risk of stroke and eligible for anticoagulation treatment (CHADS2 ≥1; n=71 493 (85%)), the proportion eligible for inclusion into RE-LY was 74% (95% CI 73.7% to 74.3%; n=52 783), compared with 72% (95% CI 71.7% to 72.3%; n=51 415) for ARISTOTLE and 56% (95% CI 55.6% to 56.4%; n=39 892) for ROCKET-AF. Conclusions Patients enrolled within RE-LY and ARISTOTLE were more reflective of the ‘real-world’ AF population in the UK, in contrast with patients enrolled within ROCKET-AF who were a more narrowly defined group of patients at higher risk of stroke. Differences between trials should be taken into account when considering the applicability of findings from randomised clinical trials. However, assessing representativeness is not a substitute for assessing generalisibility, that is, how well clinical trial results would translate into effectiveness and safety in everyday routine care. PMID:23242482

Concomitant surgical closure of left atrial appendage: A systematic review and meta-analysis.

PubMed

Ando, Masahiko; Funamoto, Masaki; Cameron, Duke E; Sundt, Thoralf M

2018-03-12

Although percutaneous closure of the left atrial appendage is supported as a potential alternative to lifelong anticoagulation in patients with atrial fibrillation, comprehensive evidence on surgical left atrial appendage closure in heart surgery is limited. We conducted a meta-analysis of studies comparing patients who underwent open cardiac surgery with or without left atrial appendage closure. A literature search was performed on PubMed, Embase, and Cochrane Trials databases. Outcomes of interest were 30-day/in-hospital mortality and cerebrovascular accident. I 2 statistics were used to evaluate heterogeneity, and publication bias was evaluated by Begg's and Egger's tests. We reviewed 1284 articles and selected for main analysis 7 articles including 3897 patients (1963 in the left atrial appendage closure group and 1934 in the non-left atrial appendage closure group). Among the 7 studies, 3 were randomized-controlled studies, 3 were propensity-matched studies, and 1 was a case-matching study. At 30-day/in-hospital follow-up, left atrial appendage closure was significantly associated with decreased risk of mortality and cerebrovascular accident (odds ratio, 0.384, 95% confidence interval, 0.233-0.631 for mortality, and odds ratio, 0.622, 95% confidence interval, 0.388-0.998 for cerebrovascular accident). Stratified analysis demonstrated that this association was more prominent in preoperative atrial fibrillation strata. Concomitant surgical left atrial appendage closure should be considered at the time of open cardiac surgery, particularly among those in atrial fibrillation preoperatively. The benefit of left atrial appendage closure for patients not in atrial fibrillation and for those undergoing nonvalvular surgery is still unclear. Further prospective investigations are indicated. Copyright © 2018. Published by Elsevier Inc.

Role of Echocardiography in the Management and Prognosis of Atrial Fibrillation

PubMed Central

Silverman, David I; Ayirala, Srilatha R; Manning, Warren J

2012-01-01

Echocardiography plays a longstanding and vital role in the management of atrial fibrillation (AF). Advances in 2D imaging, Doppler echocardiography and strain imaging have all contributed to major progress in AF treatment. Echocardiographically measured left atrial (LA) volume is a powerful predictor of maintenance of sinus rhythm following cardioversion as well as risk of thrombus formation and thromboembolism. Doppler derived parameters of atrial mechanical function including atrial ejection force provide related prognostic information. Transesophageal echocardiocardiograpy (TEE) guided cardioversion of AF allows for rapid conversion to sinus rhythm without prolonged oral anticoagulation, and TEE serves as a useful tool during catheter ablation of AF and atrial flutter. Newer measures derived from speckle tracking offer great promise in further improving the care of patients with AF. PMID:28496715

Strokes after cardioversion of atrial fibrillation--The FibStroke study.

PubMed

Palomäki, Antti; Mustonen, Pirjo; Hartikainen, Juha E K; Nuotio, Ilpo; Kiviniemi, Tuomas; Ylitalo, Antti; Hartikainen, Päivi; Lehtola, Heidi; Luite, Riho; Airaksinen, K E Juhani

2016-01-15

Cardioversion of atrial fibrillation (AF) is associated with an increased risk for stroke. We identified all cardioversions during the 30 days preceding stroke or transient ischemic attack (TIA) in patients with a previously diagnosed AF, and sought to assess the characteristics of cardioversions leading to stroke or TIA. FibStroke is a cross-sectional observational multicenter registry that included AF patients with an ischemic stroke or intracranial bleed identified from a discharge registry of four Finnish hospitals. In total 3677 consecutive AF patients suffered 3252 strokes and 956 TIA episodes during 2003–2012. This pre-specified analysis focused on the 1644 events that occurred to patients with paroxysmal or persistent AF at the time of stroke/TIA. A total of 78 strokes and 22 TIA episodes were preceded by a cardioversion. Post-cardioversion strokes accounted for 6.4% of strokes in patients with paroxysmal/persistent AF. Of the 100 cardioversions leading to an ischemic event, 77 were acute and 23 were elective, 63 events occurred in patients not using anticoagulation, and 5 patients had periprocedural INR < 2. Importantly, 21 patients were in low risk of stroke, i.e. CHA2DS2-VASc score < 2. The median delay from cardioversion to event was 2 days. All nine patients who after an unsuccessful cardioversion developed a stroke had a spontaneous cardioversion prior to stroke. Every sixteenth stroke of patients with paroxysmal/persistent AF is preceded by a cardioversion. Most post-cardioversion strokes occur in patients not using oral anticoagulation before cardioversion of acute AF.

Quality of warfarin control in atrial fibrillation patients in South East Queensland, Australia.

PubMed

Bernaitis, N; Badrick, T; Davey, A K; Anoopkumar-Dukie, S

2016-08-01

Warfarin is widely prescribed to decrease the risk of stroke in atrial fibrillation (AF) patients. Due to patient variability in response, regular monitoring is required, and time in therapeutic range (TTR) used to indicate quality of warfarin control with a TTR>60% is recommended. Recently, an Australian Government review of anticoagulants identified the need to establish current warfarin control and determine the potential place of the newer oral anticoagulants. To determine warfarin control by a pathology practice in Queensland, Australia and identify factors influencing TTR. Retrospective data were collected from Sullivan Nicolaides Pathology, a major pathology practice offering a warfarin care programme in Australia. Patients enrolled in their programme as of September 2014 were included in the study. TTR was calculated using INR test results, and test dates using the Rosendaal method with mean patient TTR were used for analysis and comparison. Exclusions were target therapeutic range outside 2.0-3.0, less than two INR tests and programme treatment time of less than 30 days. The eligible 3692 AF patients had 73.6% of INR tests within the therapeutic range. The mean TTR was 81%, with 97% of patients above a TTR of 60%. TTR was not significantly influenced by age, gender or socioeconomic factors. The observed mean TTR of over 80% is superior to the minimum recommended threshold of 60%. The TTR achieved by the Queensland pathology practice demonstrates that dedicated warfarin programmes can produce high-quality warfarin care, ensuring the full benefit of warfarin for Australian patients. © 2016 Royal Australasian College of Physicians.

Atrial fibrillation.

PubMed

Medi, Caroline; Hankey, Graeme J; Freedman, Saul B

2007-02-19

The incidence and prevalence of atrial fibrillation are increasing because of both population ageing and an age-adjusted increase in incidence of atrial fibrillation. Deciding between a rate control or rhythm control approach depends on patient age and comorbidities, symptoms and haemodynamic consequences of the arrhythmia, but either approach is acceptable. Digoxin is no longer a first-line drug for rate control: beta-blockers and verapamil and diltiazem control heart rate better during exercise. Anti-arrhythmic drugs have only a 40%-60% success rate of maintaining sinus rhythm at 1 year, and have significant side effects. The selection of optimal antithrombotic prophylaxis depends on the patient's risk of ischaemic stroke and the benefits and risks of long-term warfarin versus aspirin, but is independent of rate or rhythm control strategy. Ischaemic stroke risk is best estimated with the CHADS2 score (Congestive heart failure, Hypertension, Age > or = 75 years, Diabetes, 1 point each; prior Stroke or transient ischaemic attack, 2 points). For patients with valvular atrial fibrillation or a CHADS(2) score > or = 2, anticoagulation with warfarin is recommended (INR 2-3, higher for mechanical valves) unless contraindicated or annual major bleeding risk > 3%. Aspirin or warfarin may be used when the CHADS(2) score = 1. Aspirin, 81-325 mg daily, is recommended in patients with a CHADS(2) score of 0 or if warfarin is contraindicated. Stroke rate is similar for paroxysmal, persistent, and permanent atrial fibrillation, and probably for atrial flutter.

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

The effect of the amiodarone-warfarin interaction on anticoagulation quality in a single, high-quality anticoagulation center.

PubMed

White, Ryan D; Riggs, Kyle W; Ege, Ed J; Petroski, Gregory F; Koerber, Scott M; Flaker, Greg

2016-03-01

Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 ± 20 months (mean INR 36 ± 18) was 66 ± 16.6% compared with 61.3 ± 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 ± 20 months (mean INR 35 ± 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 ± 22.2%) was not significantly different in the first 3 months (54.6 ± 33.4%) or after 3 months (67.2 ± 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients.

A multinational investigation of time and traveling costs in attending anticoagulation clinics.

PubMed

Jowett, Sue; Bryan, Stirling; Mahé, Isabelle; Brieger, David; Carlsson, Jonas; Kartman, Bernt; Nevinson, Mark

2008-01-01

Anticoagulation is used in patients with atrial fibrillation to reduce the risk of ischemic stroke. The therapy requires regular monitoring and, frequently, dose adjustment. This study aimed to determine the time and traveling costs that patients incur to themselves and society in attending anticoagulation clinics. A subset of patients from 105 primary and secondary care clinics allocated to the warfarin arm of SPORTIF III (patients from Australia, France, Portugal, Spain, Sweden, and the UK) completed a questionnaire. Patients indicated the type of transport used for clinic visits, and estimated traveling expenses. Patients were also asked to estimate total traveling and clinic attendance time, and to confirm whether they were currently employed and whether they had to give up time from work to attend the clinic. Time cost of companions was also taken into consideration. Cost per visit was calculated (euro, 2003 prices). Questionnaires for a total of 381 patients were analyzed, with the majority of patients from Sweden (n = 130) and the UK (n = 101). Mean cost to patients varied widely between countries, ranging from euro6.9 (France) to euro20.5 (Portugal) per visit. For most countries, time costs (value of lost working and leisure time) were the main driver of costs. Mean time cost to society ranged from euro5.6 (France) to euro31.7 (Portugal) per visit. Patients incur considerable costs when visiting anticoagulation clinics, and these costs vary by country. The results suggest the importance of taking a broad economic perspective when considering the cost-effectiveness of warfarin.

Management and Outcomes of Bleeding Events in Patients in the Emergency Department Taking Warfarin or a Non-Vitamin K Antagonist Oral Anticoagulant.

PubMed

Singer, Adam J; Quinn, Adam; Dasgupta, Neil; Thode, Henry C

2017-01-01

Most comparisons of bleeding patients who are taking warfarin or a non-vitamin K oral anticoagulant (NOAC) have been limited to admitted patients and major bleeding events in well-controlled, clinical trial settings. We describe the clinical characteristics, interventions, and outcomes in patients who are taking warfarin or a NOAC who presented to the emergency department (ED) with any bleeding event. We conducted a structured, retrospective, observational study of nonvalvular atrial fibrillation, pulmonary embolism, or deep vein thrombosis warfarin- or NOAC-treated patients presenting with any bleeding event to a large, academic ED between January 2012 and March 2015. We used descriptive statistics to summarize baseline characteristics, treatments, and outcomes and performed subgroup analyses based on the type of anticoagulant and site of bleeding. The electronic search yielded 95 cases of patients taking a NOAC (i.e., dabigatran [33], rivaroxaban [32], or abixaban [30]) and 342 patients taking warfarin. Reversal agents were rarely used in all anticoagulant groups. Case fatality rates were similar among warfarin- and NOAC-treated patients for gastrointestinal bleeding (7% vs. 7%) and intracranial hemorrhage (18% vs. 4%), respectively. After adjustment for other factors, only intracranial hemorrhage (odds ratio 4.4; 95% confidence interval 1.4-13.3) was associated with mortality. Despite the rare use of reversal strategies, mortality was low and outcomes were comparable among patients with bleeding events presenting to the ED while taking a NOAC compared with warfarin. Copyright © 2016 Elsevier Inc. All rights reserved.

A Prospective Survey of Atrial Fibrillation Management for Real-world Guideline Adherence: COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) Registry.

PubMed

Kim, Hyeongsoo; Kim, Tae Hoon; Cha, Myung Jin; Lee, Jung Myung; Park, Junbeom; Park, Jin Kyu; Kang, Ki Woon; Shim, Jaemin; Uhm, Jae Sun; Kim, Jun; Park, Hyung Wook; Choi, Eue Keun; Kim, Jin Bae; Kim, Changsoo; Lee, Young Soo; Joung, Boyoung

2017-11-01

The aging population is rapidly increasing, and atrial fibrillation (AF) is becoming a significant public health burden in Asia, including Korea. This study evaluated current treatment patterns and guideline adherence of AF treatment. In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 6,275 patients with nonvalvular AF were consecutively enrolled between June 2016 and April 2017 from 10 tertiary hospitals in Korea. The AF type was paroxysmal, persistent, and permanent in 65.3%, 30.0%, and 2.9% of patients, respectively. Underlying structural heart disease was present in 11.9%. Mean CHA₂DS₂-VASc was 2.7±1.7. Oral anticoagulation (OAC), rate control, and rhythm control were used in 70.1%, 53.9%, and 54.4% of patients, respectively. OAC was performed in 82.7% of patients with a high stroke risk. However, antithrombotic therapy was inadequately used in 53.4% of patients with a low stroke risk. For rate control in 192 patients with low ejection fraction (<40%), β-blocker (65.6%), digoxin (5.2%), or both (19.3%) were adequately used in 90.1% of patients; however, a calcium channel blocker was inadequately used in 9.9%. A rhythm control strategy was chosen in 54.4% of patients. The prescribing rate of class Ic antiarrythmics, dronedarone, and sotalol was 16.9% of patients with low ejection fraction. This study shows how successfully guidelines can be applied in the real world. The nonadherence rate was 17.2%, 9.9%, and 22.4% for stroke prevention, rate control, and rhythm control, respectively. Copyright © 2017. The Korean Society of Cardiology

Management of Stroke Prevention in Canadian Patients with Atrial Fibrillation at Moderate to High Risk of Stroke

PubMed Central

Semchuk, William M; Levac, Brandon; Lara, Muria; Shakespeare, Annabelle; Evers, Thomas; Bolt, Jennifer

2013-01-01

Background Many patients with atrial fibrillation who are at moderate to high risk of stroke do not receive anticoagulation with vitamin K antagonists (VKAs) in accordance with recommendations. Objective: To determine (1) why Canadian patients with atrial fibrillation who are potentially eligible for VKA do not receive this therapy, (2) why Canadian primary care physicians discontinue VKA therapy, and (3) why VKA therapy is perceived as difficult to manage. Methods: The study involved a chart review of 3 cohorts of patients with nonvalvular atrial fibrillation at moderate to high risk of stroke: patients who had never received VKA treatment (VKA-naive), those whose treatment had been discontinued, and those whose VKA treatment was considered difficult to manage. Results: Charts for 187 patients (mean age 78.4 years, standard deviation 8.9 years) treated at 39 primary care sites were reviewed (62 treatment-naive, 42 with therapy discontinued, and 83 whose therapy was considered difficult to manage). Atrial fibrillation was paroxysmal in 82 (44%) of the patients, persistent in 47 patients (25%), and permanent in 58 (31%). One patient in each of the 3 cohorts had experienced a stroke during the 6 months before study participation. Bleeding events were more frequent among patients who had discontinued VKA therapy than in the other 2 groups. Among those whose therapy was discontinued and those whose therapy was difficult to manage, the mean time in the therapeutic range was 46.3% and 56.4%, respectively. The most common reason for not initiating VKA therapy in treatment-naive patients was the transient nature of atrial fibrillation (25/62 [40%]). The most common reason for discontinuation of VKA therapy was a bleeding event (10/42 [24%]). The presence of a concomitant chronic disease was the most common reason that a patient’s therapy was considered difficult to manage (46/83 [55%]). Conclusions: VKA therapy was not initiated or was discontinued for various reasons. Multiple comorbid conditions made management of VKA therapy more difficult. These findings reflect the challenges that primary care physicians experience in managing the care of patients with atrial fibrillation. PMID:24159232

Management of stroke prevention in canadian patients with atrial fibrillation at moderate to high risk of stroke.

PubMed

Semchuk, William M; Levac, Brandon; Lara, Muria; Shakespeare, Annabelle; Evers, Thomas; Bolt, Jennifer

2013-09-01

Many patients with atrial fibrillation who are at moderate to high risk of stroke do not receive anticoagulation with vitamin K antagonists (VKAs) in accordance with recommendations. To determine (1) why Canadian patients with atrial fibrillation who are potentially eligible for VKA do not receive this therapy, (2) why Canadian primary care physicians discontinue VKA therapy, and (3) why VKA therapy is perceived as difficult to manage. The study involved a chart review of 3 cohorts of patients with nonvalvular atrial fibrillation at moderate to high risk of stroke: patients who had never received VKA treatment (VKA-naive), those whose treatment had been discontinued, and those whose VKA treatment was considered difficult to manage. Charts for 187 patients (mean age 78.4 years, standard deviation 8.9 years) treated at 39 primary care sites were reviewed (62 treatment-naive, 42 with therapy discontinued, and 83 whose therapy was considered difficult to manage). Atrial fibrillation was paroxysmal in 82 (44%) of the patients, persistent in 47 patients (25%), and permanent in 58 (31%). One patient in each of the 3 cohorts had experienced a stroke during the 6 months before study participation. Bleeding events were more frequent among patients who had discontinued VKA therapy than in the other 2 groups. Among those whose therapy was discontinued and those whose therapy was difficult to manage, the mean time in the therapeutic range was 46.3% and 56.4%, respectively. The most common reason for not initiating VKA therapy in treatment-naive patients was the transient nature of atrial fibrillation (25/62 [40%]). The most common reason for discontinuation of VKA therapy was a bleeding event (10/42 [24%]). The presence of a concomitant chronic disease was the most common reason that a patient's therapy was considered difficult to manage (46/83 [55%]). VKA therapy was not initiated or was discontinued for various reasons. Multiple comorbid conditions made management of VKA therapy more difficult. These findings reflect the challenges that primary care physicians experience in managing the care of patients with atrial fibrillation.

Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

PubMed

Singer, Daniel E; Albers, Gregory W; Dalen, James E; Fang, Margaret C; Go, Alan S; Halperin, Jonathan L; Lip, Gregory Y H; Manning, Warren J

2008-06-01

This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the American College of Chest Physicians Evidence-Based Guidelines Clinical Practice Guidelines (8th Edition). Grade 1 recommendations indicate that most patients would make the same choice and Grade 2 suggests that individual patient's values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range 2.0-3.0, unless otherwise noted). In patients with AF, including those with paroxysmal AF, who have had a prior ischemic stroke, transient ischemic attack (TIA), or systemic embolism, we recommend long-term anticoagulation with an oral VKA, such as warfarin, because of the high risk of future ischemic stroke faced by this set of patients (Grade 1A). In patients with AF, including those with paroxysmal AF, who have two or more of the risk factors for future ischemic stroke listed immediately below, we recommend long-term anticoagulation with an oral VKA (Grade 1A). Two or more of the following risk factors apply: age >75 years, history of hypertension, diabetes mellitus, moderately or severely impaired left ventricular systolic function and/or heart failure. In patients with AF, including those with paroxysmal AF, with only one of the risk factors listed immediately above, we recommend long-term antithrombotic therapy (Grade 1A), either as anticoagulation with an oral VKA, such as warfarin (Grade 1A), or as aspirin, at a dose of 75-325 mg/d (Grade 1B). In these patients at intermediate risk of ischemic stroke we suggest a VKA rather than aspirin (Grade 2A). In patients with AF, including those with paroxysmal AF, age < or =75 years and with none of the other risk factors listed above, we recommend long-term aspirin therapy at a dose of 75-325 mg/d (Grade 1B), because of their low risk of ischemic stroke. For patients with atrial flutter, we recommend that antithrombotic therapy decisions follow the same risk-based recommendations as for AF (Grade 1C). For patients with AF and mitral stenosis, we recommend long-term anticoagulation with an oral VKA (Grade 1B). For patients with AF and prosthetic heart valves we recommend long-term anticoagulation with an oral VKA at an intensity appropriate for the specific type of prosthesis (Grade 1B). See CHEST 2008; 133(suppl):593S-629S. For patients with AF of > or =48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA, such as warfarin, for 3 weeks before elective cardioversion and for at least 4 weeks after sinus rhythm has been maintained (Grade 1C). For patients with AF of > or = 48 h or of unknown duration undergoing pharmacological or electrical cardioversion, we also recommend either immediate anticoagulation with unfractionated IV heparin, or low-molecular-weight heparin (LMWH), or at least 5 days of warfarin by the time of cardioversion (achieving an INR of 2.0-3.0) as well as a screening multiplane transesophageal echocardiography (TEE). If no thrombus is seen, cardioversion is successful, and sinus rhythm is maintained, we recommend anticoagulation for at least 4 weeks. If a thrombus is seen on TEE, then cardioversion should be postponed and anticoagulation should be continued indefinitely. We recommend obtaining a repeat TEE before attempting later cardioversion (Grade 1B addressing the equivalence of TEE-guided vs non-TEE-guided cardioversion). For patients with AF of known duration <48 h, we suggest cardioversion without prolonged anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or LMWH at presentation (Grade 2C).

Contemporary utilization of antithrombotic therapy for stroke prevention in patients with atrial fibrillation: an audit in an Australian hospital setting.

PubMed

Pandya, Ekta Yogeshkumar; Anderson, Elizabeth; Chow, Clara; Wang, Yishen; Bajorek, Beata

2018-02-01

To document antithrombotic utilization in patients with nonvalvular atrial fibrillation (NVAF), particularly, recently approved NOACs (nonvitamin K antagonist oral anticoagulants) and warfarin; and identify factors predicting the use of NOACs versus warfarin. A retrospective audit was conducted in an Australian hospital. Data pertaining to inpatients diagnosed with atrial fibrillation (AF) admitted between January and December 2014 were extracted. This included patient demographics, risk factors (stroke, bleeding), social history, medical conditions, medication history, medication safety issues, medication adherence, and antithrombotic prescribed at admission and discharge. Among 199 patients reviewed, 84.0% were discharged on antithrombotics. Anticoagulants (± antiplatelets) were most frequently (52.0%) prescribed (two-thirds were prescribed warfarin, the remainder NOACs), followed by antiplatelets (33.0%). Among 41 patients receiving NOACs, 59.0% were prescribed rivaroxaban, 24.0% dabigatran, and 17.0% apixaban. Among patients aged 75 years and over, antiplatelets were most frequently used (37.0%), followed by warfarin (33.0%), then NOACs (14.0%). Compared with their younger counterparts, patients aged 75 years and over were significantly less likely to receive NOACs (14.0% versus 28.0%, p = 0.01). Among the 'most eligible' patients (Congestive Cardiac Failure, Hypertension (, Age ⩾ 75 years, Age= 65-74 years, Diabetes Mellitus, Stroke/ Transient Ischaemic Attack/ Thromboembolism, Vascular disease, Sex female[CHA 2 DS 2 -VASc] score ⩾2 and no bleeding risk factors), 46.0% were not anticoagulated on discharge. Patients with anaemia (68.0% versus 86.0%, p = 0.04) or a history of bleeding (65.0% versus 87.0%, p = 0.01) were less likely to receive antithrombotics compared with those without these risk factors. Warfarin therapy was less frequently prescribed among patients with cognitive impairment compared with patients with no cognitive issues (12.0% versus 23.0%, p = 0.01). Multivariate logistic regression modelling identified that patients with renal impairment were 3.6 times more likely to receive warfarin compared with NOACs (odds ratio = 3.6, 95% confidence interval = 0.08-0.90, p = 0.03, 60.0% correctly predicted; Cox and Snell R 2 = 0.51, Nagelkerke R 2 = 0.69). Despite the availability of NOACs, warfarin remains a preferred treatment option, particularly among patients with renal impairment. The high proportion of eligible patients still being prescribed antiplatelet therapy or 'no therapy' needs to be addressed.

Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

PubMed

Miyamoto, Koji; Aiba, Takeshi; Arihiro, Shoji; Watanabe, Makoto; Kokubo, Yoshihiro; Ishibashi, Kohei; Hirose, Sayako; Wada, Mitsuru; Nakajima, Ikutaro; Okamura, Hideo; Noda, Takashi; Nagatsuka, Kazuyuki; Noguchi, Teruo; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kamakura, Shiro; Shimizu, Wataru; Miyamoto, Yoshihiro; Toyoda, Kazunori; Kusano, Kengo

2016-08-01

Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) ≥ 50 ml/min (mean age 68 ± 11 years, mean CHADS2 score = 1.8 ± 1.4, CHA2DS2-VASc score = 2.8 ± 1.8, HAS-BLED score = 1.7 ± 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr ≥ 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 ± 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr ≥ 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and ≥3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1-2, 3-4 and ≥5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr ≥ 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was not uncommon and was associated with more frequent adverse events including major bleeding in NVAF patients with anticoagulation therapy. CHADS2, CHA2DS2-VASc, and HAS-BLED scores may be useful as an index of predicting renal function deterioration.

The 'obesity paradox' in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial.

PubMed

Sandhu, Roopinder K; Ezekowitz, Justin; Andersson, Ulrika; Alexander, John H; Granger, Christopher B; Halvorsen, Sigrun; Hanna, Michael; Hijazi, Ziad; Jansky, Petr; Lopes, Renato D; Wallentin, Lars

2016-10-07

The prognostic implication of adiposity on clinical outcomes in atrial fibrillation (AF) patients treated with oral anticoagulation is unclear. A total of 17 913 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial had body mass index (BMI) measured at baseline. For the primary analysis, BMI was categorized as normal (18.5 to <25 kg/m 2 ), overweight (25 to <30 kg/m 2 ), and obese (≥30 kg/m 2 ). Waist circumference (WC) was defined as high if >102 cm for men and >88 cm in women. Outcomes were stroke or systemic embolism, a composite endpoint (stroke, systemic embolism, myocardial infarction, or all-cause mortality), all-cause mortality, and major bleeding. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) across categories of BMI and WC adjusting for established risk factors and treatment allocation. At baseline, 4052 (22.6%) patients had a normal BMI, 6702 (37.4%) were overweight, and 7159 (40.0%) were obese. In multivariable analyses, higher BMI was associated with a lower risk of all-cause mortality [overweight: HR 0.67 (95% CI 0.59-0.78); obese: HR 0.63 (95% CI 0.54-0.74), P < 0.0001] and the composite endpoint [overweight: HR 0.74 (95% CI 0.65-0.84); obese: HR 0.68 (95% CI 0.60-0.78), P < 0.0001] compared with normal BMI. In women, high WC was associated with a 31% lower risk of all-cause mortality (P = 0.001), 27% lower risk of the composite endpoint (P = 0.001), and 28% lower risk of stroke or systemic embolism (P = 0.048) but not in men. There was no significant association between adiposity and major bleeding. In patients with AF treated with oral anticoagulants, higher BMI and WC are associated with a more favourable prognosis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial.

PubMed

Vinereanu, Dragos; Stevens, Susanna R; Alexander, John H; Al-Khatib, Sana M; Avezum, Alvaro; Bahit, Marıa Cecilia; Granger, Christopher B; Lopes, Renato D; Halvorsen, Sigrun; Hanna, Michael; Husted, Steen; Hylek, Elaine M; Mărgulescu, Andrei D; Wallentin, Lars; Atar, Dan

2015-12-07

To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation. Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double-blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive either warfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74-1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all-cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex. In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women. ARISTOTLE ClinicalTrials.gov number, NCT00412984. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

The future of anticoagulation management in atrial fibrillation in Europe: An assessment of today's challenges with recommendations for the future.

PubMed

Lichten, Catherine A; Castle-Clarke, Sophie; Manville, Catriona; Horvath, Veronika; Robin, Enora; Krapels, Joachim; Parks, Sarah; Sim, Megan; van Zijverden, Olga; Chataway, Joanna

2015-11-30

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, affecting approximately 1-2 per cent of the population worldwide. Those who suffer from AF have a five times higher risk of stroke. AF prevalence increases with age and it affects roughly 18 per cent of the population over 85. Consequently, as populations age, AF is becoming an increasingly significant public health issue. Over recent years there have been developments in treatment and management options, both for treating the arrhythmia directly, and assessing and reducing the risk of AF-related stroke, but there is a need to ensure that available knowledge is applied optimally to benefit patients so that opportunities to prevent AF-related stroke are not missed. The aims of this project were to assess the current landscape and explore the direction of future developments in AF management in Europe, with a focus on the use of anticoagulants in the prevention of AF-related stroke. Through rapid evidence assessment, key informant interviews, PESTLE analysis and the development and exploration of future scenarios, we have developed sets of shorter- and longer-term recommendations for improving AF-related patient outcomes. The short-term recommendations are: i) improve AF awareness among the public and policymakers; ii) support education about AF management for healthcare professionals and patients; and iii) maintain engagement in AF-related research across the health services.

Dabigatran reversal with idarucizumab in a patient undergoing heart transplantation: first European report.

PubMed

Tralhão, António; Aguiar, Carlos; Ferreira, Jorge; Rebocho, Maria José; Santos, Emília; Martins, Dinis; Neves, José Pedro

2017-01-01

Dabigatran is a direct thrombin inhibitor with a favorable effectiveness and safety profile when compared to vitamin K antagonists, both in randomized trials and real world registries of atrial fibrillation patients. Yet, physicians' fear of high bleeding risk scenarios in daily clinical practice still precludes a more widespread use of oral anticoagulation. We hereby report a successful case of dabigatran reversal with the novel monoclonal antibody fragment idarucizumab in a patient undergoing heart transplantation. A 45-year old male patient on dabigatran for atrial fibrillation thromboprophylaxis was enlisted for heart transplantation due to end-stage ischemic heart failure. Upon donor availability and suitability and following the last intake of the drug 12 h previously, activated partial thromboplastin time was measured and found to be elevated. After general anesthesia and before extracorporeal circulation, idarucizumab was administered as two boluses of 2.5 g. Orthotopic heart transplantation ensued under full heparinization and cardiopulmonary bypass. Total chest tube output was 1125 mL after 3 days and 4 units of fresh frozen plasma and one platelet pool were administered in the operating room without further need for blood products. The post-operative period was uneventful. Idarucizumab was associated with an effective hemostasis in the setting of heart transplantation. Dabigatran may be considered as an alternative to vitamin K antagonists in heart transplant candidates with an indication for oral anticoagulation.

Using an Atrial Fibrillation Decision Support Tool for Thromboprophylaxis in Atrial Fibrillation: Effect of Sex and Age.

PubMed

Eckman, Mark H; Lip, Gregory Y H; Wise, Ruth E; Speer, Barbara; Sullivan, Megan; Walker, Nita; Kissela, Brett; Flaherty, Matthew L; Kleindorfer, Dawn; Baker, Peter; Ireton, Robert; Hoskins, Dave; Harnett, Brett M; Aguilar, Carlos; Leonard, Anthony; Arduser, Lora; Steen, Dylan; Costea, Alexandru; Kues, John

2016-05-01

To assess the appropriateness of oral anticoagulant therapy (OAT) in women and elderly adults, looking for patterns of undertreatment or unnecessary treatment. Retrospective cohort study. Primary care practices of an academic healthcare system. Adults (aged 28-93) with nonvalvular atrial fibrillation (AF) seen between March 2013 and February 2014 (N = 1,585). Treatment recommendations were made using an AF decision support tool (AFDST) based on projections of quality-adjusted life expectancy calculated using a decision analytical model that integrates individual-specific risk factors for stroke and hemorrhage. Treatment was discordant from AFDST-recommended treatment in 45% (326/725) of women and 39% (338/860) of men (P = .02). Although current treatment was discordant from recommended in 35% (89/258) of participants aged 85 and older and in 43% (575/1,328) of those younger than 85 (P = .01), many undertreated elderly adults were receiving aspirin as the sole antithrombotic agent. Physicians should understand that female sex is a significant risk factor for AF-related stroke and incorporate this into decision-making about thromboprophylaxis. Treating older adults with aspirin instead of OAT exposes them to significant risk of bleeding with little to no reduction in AF-related stroke risk. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Atrial Fibrillation in Hematologic Malignancies, Especially After Autologous Hematopoietic Stem Cell Transplantation: Review of Risk Factors, Current Management, and Future Directions.

PubMed

Mathur, Pankaj; Paydak, Hakan; Thanendrarajan, Sharmilan; van Rhee, Frits

2016-02-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with significant morbidity and mortality worldwide. In addition to well-established risk factors, cancer has been increasingly associated with the development of AF. Its increased occurrence in those with hematologic malignancies has been attributed to chemotherapeutic agents and autologous hematopoietic stem cell transplantation (AHSCT). Recently, a few studies have attempted to define the etiopathogenesis of AF in hematologic malignancies. The management of AF in these patients is challenging because of the concurrent complicating factors, such as thrombocytopenia, orthostatic hypotension, and cardiac amyloidosis. More studies are needed to define the management of AF, especially rate versus rhythm control and anticoagulation. Arrhythmias, in particular, AF, have been associated with an increased length of stay, increased intensive care unit admissions, and greater cardiovascular mortality. In the present review, we describe AF in patients with hematologic malignancies, the risk factors, especially after AHSCT, and the current management of AF. Copyright © 2016 Elsevier Inc. All rights reserved.

ABO blood groups: A risk factor for left atrial and left atrial appendage thrombogenic milieu in patients with non-valvular atrial fibrillation.

PubMed

Fu, Yuan; Li, Kuibao; Yang, Xinchun

2017-08-01

Previous studies have identified ABO blood groups as predictors of thromboembolic diseases. In patients with atrial fibrillation (AF), however, potential association between ABO blood groups and the risk of left atrial (LA) and/or left atrial appendage (LAA) thrombogenic milieu (TM) has not been established. This is a retrospective case-control study that included 125 consecutive patients with non-valvular atrial fibrillation (NVAF) plus TM, as evidenced by transesophageal echocardiography (TEE) during a period from1 January 2010 to 31 December 2016. The controls were selected randomly from 1072 NVAF without TM at a 1:2 ratio. Potential association between ABO blood groups and TM was analyzed using multivariate logistic regression analysis. The risk of TM was higher in patients with blood group A (33.6% vs. 20.2% in non-A blood groups, P=0.005). After adjusting for age, sex, oral anticoagulant use, AF type and duration, and relevant functional measures (e.g., NT-pro BNP level, left atrium diameter, and left ventricular ejection fraction), blood group A remained associated with an increased risk of TM (OR=2.99, 95% CI 1.4-6.388, P=0.005). Blood group A is an independent risk factor for TM in NVAF patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators.

PubMed

Hart, R G; Pearce, L A; Rothbart, R M; McAnulty, J H; Asinger, R W; Halperin, J L

2000-01-01

This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation (AF). Although intermittent AF is common, relatively little is known about the attendant risk of stroke. A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years. Independent risk factors for ischemic stroke were identified by multivariate analysis. Patients with intermittent AF were, on average, younger (66 vs. 70 years, p < 0.001), were more often women (37% vs. 26% p < 0.001) and less often had heart failure (11% vs. 21%, p < 0.001) than those with sustained AF. The annualized rate of ischemic stroke was similar for those with intermittent (3.2%) and sustained AF (3.3%). In patients with intermittent AF, independent predictors of ischemic stroke were advancing age (relative risk [RR] = 2.1 per decade, p < 0.001), hypertension (RR = 3.4, p = 0.003) and prior stroke (RR = 4.1, p = 0.01). Of those with intermittent AF predicted to be high risk (24%), the observed stroke rate was 7.8% per year (95% confidence interval 4.5 to 14). In this large cohort of AF patients given aspirin, those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors. Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation. High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF.

The Population-Based Long-Term Impact of Anticoagulant and Antiplatelet Therapies in Low-Risk Patients With Atrial Fibrillation.

PubMed

Golive, Anjani; May, Heidi T; Bair, Tami L; Jacobs, Victoria; Crandall, Brian G; Cutler, Michael J; Day, John D; Mallender, Charles; Osborn, Jeffrey S; Stevens, Scott M; Weiss, J Peter; Woller, Scott C; Bunch, T Jared

2017-07-01

Among patients with atrial fibrillation (AF), the risk of stroke risk is a significant concern. CHADS 2 and CHA 2 DS 2 -VASc ≤2 scoring have been used to stratify patients into categories of risk. Without randomized, prospective data, the need and type of long-term antithrombotic medications for thromboembolism prevention in lower risk AF patients remains controversial. We sought to define the long-term impact of anticoagulant and antiplatelet therapy use in AF patients at low risk of stroke. A total of 56,764 patients diagnosed with AF and a CHADS 2 score of 0 or 1, or CHA 2 DS 2 -VASc score of 0, 1, or 2 were studied. Antithrombotic therapy was defined as aspirin, clopidogrel (antiplatelet therapy), or warfarin monotherapy (anticoagulation) initiated within 6 months of AF diagnosis. End points included all-cause mortality, cerebrovascular accident, transient ischemic attack (TIA), and major bleed. The average age of the population was 67.0 ± 14.1 years and 56.6% were male. In total, 9,682 received aspirin, 1,802 received clopidogrel, 1,164 received warfarin, and 46,042 did not receive any antithrombotic therapy. Event rates differed between patients with a CHADS 2 score of 0 and 1; 18.5% and 37.8% had died, 1.7% and 3.4% had a stroke, 2.2% and 3.2% had a TIA, and 14% and 12.5% had a major bleed, respectively (p <0.0001 for all). The rates of stroke, TIA, and major bleeding increased as antithrombotic therapy intensity increased from no therapy, to aspirin, to clopidogrel, and to warfarin (all p <0.0001). Similar outcomes were observed in low-risk CHA 2 DS 2 -VASc scores (0 to 2). In low-risk AF patients with a CHADS 2 score of 0 to 1 or CHA 2 DS 2 -VASc score of 0 to 2, the use of aspirin, clopidogrel, and warfarin was not associated with lower stroke rates at 5 years compared with no therapy. However, the use of antithrombotic agents was associated with a significant risk of bleed. Copyright © 2017 Elsevier Inc. All rights reserved.

Meta-analysis of safety and efficacy for direct oral anticoagulation treatment of non-valvular atrial fibrillation in relation to renal function.

PubMed

Zou, Rongjun; Tao, Jun; Shi, Wanting; Yang, Minglei; Li, Hongmu; Lin, Xifeng; Yang, Songran; Hua, Ping

2017-12-01

We performed a meta-analysis of the safety and efficacy of anticoagulation treatment for atrial fibrillation (AF) in relation to renal function. We also examined the change in estimated glomerular filtration rate (eGFR) from baseline and compared the outcomes for patients with stable and worsening renal function. We selected studies that used randomized controlled trials in which outcomes for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, or edoxaban) were compared with those for warfarin in AF patients with normal, mild or moderate renal function, except the severe one (creatinine clearance<30). We assessed five clinical trials, involving 72,608 patients. Pooled analysis indicated that the risk of stroke was lower for DOACs than for warfarin among patients with mild renal impairment (Risk ratio, 0.79; 95% confidence interval, 0.68-0.91) and moderate renal impairment (0.80, 0.69-0.92). No major differences were found in patients with normal renal function. Additionally, DOACs were associated with fewer major bleeds among patients with normal (0.77, 0.70-0.84), mild (0.86, 0.77-0.95), and moderate renal impairment (0.73, 0.65-0.82). Among those treated with DOACs, a lower dosage was associated with lower risk of major bleeding (0.75, 0.68-0.83) and higher risk of stroke or systemic embolism (1.28, 1.12-1.47). Further, DOACs tended to be associated with a lower estimated glomerular filtration rate (eGFR) than warfarin even after 30months. Finally, we found significant differences in the risk of stroke (2.09, 1.64-2.68) and major bleeding (2.01, 1.66-2.42) between patients with stable and worsening renal function. DOACs have a greater clinical benefit than warfarin with respect to renal function. They are associated with a comparatively lower risk of stroke and major bleeding, as well lower eGFR. This suggests these agents are a better choice in patients with renal disease. Copyright © 2017. Published by Elsevier Ltd.

Direct Oral Anticoagulants in Emergency Trauma Admissions.

PubMed

Maegele, Marc; Grottke, Oliver; Schöchl, Herbert; Sakowitz, Oliver A; Spannagl, Michael; Koscielny, Jürgen

2016-09-05

Direct (non-vitamin-K-dependent) oral anticoagulants (DOAC) are given as an alternative to vitamin K antagonists (VKA) to prevent stroke and embolic disease in patients with atrial fibrillation that is not due to pathology of the heart valves. Fatal hemorrhage is rarer when DOACs are given (nonvalvular atrial fibrillation: odds ratio [OR] 0.68; 95% confidence interval [95% CI: 0.48; 0.96], and venous thromboembolism: OR 0.54; [0.22; 1.32]). 48% of emergency trauma patients need an emergency operation or early surgery. Clotting disturbances elevate the mortality of such patients to 43%, compared to 17% in patients without a clotting disturbance. This underscores the impor tance of the proper, targeted treatment of trauma patients who are aking DOAC. This review is based on articles retrieved by a selective search in PubMed and on a summary of expert opinion and the recommendations of the relevant medical specialty societies. Peak DOAC levels are reached 2-4 hours after the drug is taken. In patients with normal renal and hepatic function, no drug accumulation, and no drug interactions, the plasma level of DOAC 24 hours after administration is generally too low to cause any clinically relevant risk of bleeding. The risk of drug accumulation is higher in patients with renal dysfunction (creatinine clearance [CrCl] of 30 mL/min or less). Dabigatran levels can be estimated from the thrombin time, ecarin clotting time, and diluted thrombin time, while levels of factor Xa inhibitors can be estimated by means of calibrated chromogenic anti-factor Xa activity tests. Routine clotting studies do not reliably reflect the anticoagulant activity of DOAC. Surgery should be postponed, if possible, until at least 24-48 hours after the last dose of DOAC. For patients with mild, non-life threatening hemorrhage, it suffices to discontinue DOAC; for patients with severe hemorrhage, there are special treatment algorithms that should be followed. DOACs in the setting of hemorrhage are a clinical challenge in the traumatological emergency room because of the inadequate validity of the relevant laboratory tests. An emergency antidote is now available only for dabigatran.

Lysability of fibrin clots is a potential new determinant of stroke risk in atrial fibrillation.

PubMed

Skov, Jane; Sidelmann, Johannes J; Bladbjerg, Else-Marie; Jespersen, Jørgen; Gram, Jørgen

2014-09-01

Atrial fibrillation increases the risk of ischemic stroke, but the risk depends on other factors as well. Present risk stratification schemes use age and co-morbidities, but not biochemical markers. We investigated the hypothesis that the formation, structure and lysability of fibrin clots are potential determinants of stroke risk in patients with atrial fibrillation. A total of 179 patients with atrial fibrillation in stable anticoagulant treatment were included. Thirty-two had a previous ischemic stroke. We measured thrombin generation, plasma concentrations of fibrinogen and C-reactive protein and analysed fibrin structure and lysability by turbidity. Fibrinolytic capacity was measured using the euglobulin fraction of plasma expressed in terms of t-PA equivalents (IU/ml). The patients with previous stroke had a slightly higher burden of co-morbidities compared with the remaining patients as indicated by the CHA2DS2-VASc score, but no significant differences were found regarding age, fibrinogen concentration, C-reactive protein, thrombin generation or fibrinolytic capacity. Furthermore, the patients with previous stroke had a higher mass/length ratio of fibrin fibers (5.5 vs. 5.1 x10(12) Da/cm, p=0.044) and an increased lysability (79.3 vs. 55.3%, p<0.01). The higher lysability of fibrin clots in atrial fibrillation patients with previous stroke is most likely a result of a difference in fibrin fiber properties. An increased lysability may increase the risk of embolization of clots formed in the atria, and therefore fibrin clot structure seems to be a determinant of stroke risk in atrial fibrillation. Copyright © 2014 Elsevier Ltd. All rights reserved.

The anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban or rivaroxaban.

PubMed

Brendel, L C; Dobler, F; Hessling, G; Michel, J; Braun, S L; Steinsiek, A L; Groha, P; Eckl, R; Deisenhofer, I; Hyseni, A; Roest, M; Ott, I; Steppich, B

2017-09-01

Measuring the anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban and rivaroxaban is challenging, since the activated coagulation time (ACT) does not seem to reflect the true anticoagulant activity of these drugs. We therefore evaluated coagulation properties of apixaban and rivaroxaban during RFA by different coagulation assays to better monitor periprocedural hemostasis. The study included 90 patients (61 ± 12 years) with atrial fibrillation who underwent RFA procedures. Patients received 20 mg rivaroxaban (n = 73) once or 5 mg apixaban (n = 17) twice daily 4 weeks prior to the procedure. During RFA, unfractionated heparin i.v. was given to maintain an ACT of 250-300 s. Blood samples were taken before and 10, 60, and 360 min after heparin administration. Heparin displayed a lower anti-Xa activity in rivaroxaban-treated patients compared to apixaban-treated patients. In contrast, D-dimer and prothrombin fragment F1+2 plasma levels indicated a higher activation of the coagulation cascade in apixaban/heparin than in rivaroxaban/heparin patients. This discordant coagulative state measured in vitro had no clinical impact in terms of bleeding or thromboembolic complications. We found different biochemical responses to rivaroxaban/heparin and apixaban/heparin during RFA. Precaution is necessary when monitoring periprocedural hemostasis in DOAC patients to avoid mismanagement.

[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.

Anti-arrhythmic strategies for atrial fibrillation

PubMed Central

Grandi, Eleonora; Maleckar, Mary M.

2016-01-01

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with increased risk of cerebrovascular stroke, and with several other pathologies, including heart failure. Current therapies for AF are targeted at reducing risk of stroke (anticoagulation) and tachycardia-induced cardiomyopathy (rate or rhythm control). Rate control, typically achieved by atrioventricular nodal blocking drugs, is often insufficient to alleviate symptoms. Rhythm control approaches include antiarrhythmic drugs, electrical cardioversion, and ablation strategies. Here, we offer several examples of how computational modeling can provide a quantitative framework for integrating multi scale data to: (a) gain insight into multi-scale mechanisms of AF; (b) identify and test pharmacological and electrical therapy and interventions; and (c) support clinical decisions. We review how modeling approaches have evolved and contributed to the research pipeline and preclinical development and discuss future directions and challenges in the field. PMID:27612549

Service provision and use of anticoagulants in atrial fibrillation.

PubMed Central

Sudlow, C. M.; Rodgers, H.; Kenny, R. A.; Thomson, R. G.

1995-01-01

Several large trials have shown that the risk of stroke in patients with non-valvar atrial fibrillation is reduced by treatment with warfarin. Implementing this research evidence requires not only an understanding of the trials' results and of the changes that they imply for clinicians' treatment decisions but also an appreciation of the organisation, quantity, and quality of services required to support these changes. Understanding of these implications is crucial for developing services that allow changes in practice to produce reductions in stroke incidence while minimising the risks of treatment. This article considers the developments in service provision that will probably be required to support the changes in clinical practice suggested by the trials' results. These services will be provided largely by doctors, and their development has implications for doctors in both primary and secondary care. Images FIG 1 PMID:7663216

The Changing Landscape for Stroke Prevention in AF: Findings From the GLORIA-AF Registry Phase 2.

PubMed

Huisman, Menno V; Rothman, Kenneth J; Paquette, Miney; Teutsch, Christine; Diener, Hans-Christoph; Dubner, Sergio J; Halperin, Jonathan L; Ma, Chang Sheng; Zint, Kristina; Elsaesser, Amelie; Bartels, Dorothee B; Lip, Gregory Y H

2017-02-21

GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non-vitamin K antagonist oral anticoagulant (NOAC), became available. This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients' baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA 2 DS 2 -VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score ≥2; 86.1%); 13.9% had moderate risk (CHA 2 DS 2 -VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Imaging of Hemorrhagic Stroke.

PubMed

Hakimi, Ryan; Garg, Ankur

2016-10-01

Hemorrhagic stroke comprises approximately 15% to 20% of all strokes. This article provides readers with an understanding of the indications and significance of various neuroimaging techniques available for patients presenting with hemorrhagic strokes of distinct causes. The most common initial neuroimaging study is a noncontrast head CT, which allows for the identification of hemorrhage. Once an intracranial hemorrhage has been identified, the pattern of blood and the patient's medical history, neurologic examination, and laboratory studies lead the practitioner to pursue further neuroimaging studies to guide the medical, surgical, and interventional management. Given that hemorrhagic stroke constitutes a heterogeneous collection of diagnoses, the subsequent neuroimaging pathway necessary to better evaluate and care for these patients is variable based on the etiology.With an increasing incidence and prevalence of atrial fibrillation associated with the aging population and the introduction of three new direct factor Xa inhibitors and one direct thrombin inhibitor to complement vitamin K antagonists, oral anticoagulant use continues to increase. Patients on oral anticoagulants have a sevenfold to tenfold increased risk for intracerebral hemorrhage (ICH). Furthermore, patients who have an ICH associated with oral anticoagulant use have a higher mortality rate than those with primary ICH. Despite the reduced incidence of hypertension-related ICH over the past decade, it is expected that the incidence of ICH will continue to increase. Neuroimaging studies are integral to the identification of hemorrhagic stroke, determination of the underlying etiology, prevention of hematoma expansion, treatment of acute complications, and treatment of the underlying etiology, if indicated. Neuroimaging is essential for prognostication and thus directly impacts patient care.

New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events.

PubMed

Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I

2015-01-01

Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required to further assess the efficacy of NOACs.

New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events

PubMed Central

Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I

2015-01-01

Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required to further assess the efficacy of NOACs. PMID:26150723

Guidelines for the preventive treatment of ischaemic stroke and TIA (II). Recommendations according to aetiological sub-type.

PubMed

Fuentes, B; Gállego, J; Gil-Nuñez, A; Morales, A; Purroy, F; Roquer, J; Segura, T; Tejada, J; Lago, A; Díez-Tejedor, E; Alonso de Leciñana, M; Alvarez-Sabin, J; Arenillas, J; Calleja, S; Casado, I; Castellanos, M; Castillo, J; Dávalos, A; Díaz-Otero, F; Egido, J A; López-Fernández, J C; Freijo, M; García Pastor, A; Gilo, F; Irimia, P; Maestre, J; Masjuan, J; Martí-Fábregas, J; Martínez-Sánchez, P; Martínez-Vila, E; Molina, C; Nombela, F; Ribó, M; Rodríguez-Yañez, M; Rubio, F; Serena, J; Simal, P; Vivancos, J

2014-04-01

To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and Transient Ischaemic Attack (TIA). We reviewed the available evidence on ischaemic stroke and TIA prevention according to aetiological subtype. Levels of evidence and recommendation levels are based on the classification of the Centre for Evidence-Based Medicine. In atherothrombotic IS, antiplatelet therapy and revascularization procedures in selected cases of ipsilateral carotid stenosis (70%-90%) reduce the risk of recurrences. In cardioembolic IS (atrial fibrillation, valvular diseases, prosthetic valves and myocardial infarction with mural thrombus) prevention is based on the use of oral anticoagulants. Preventive therapies for uncommon causes of IS will depend on the aetiology. In the case of cerebral venous thrombosis oral anticoagulation is effective. We conclude with recommendations for clinical practice in prevention of IS according to the aetiological subtype presented by the patient. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

An Unusual Consolidation: Lobar Pulmonary Hemorrhage Due to Antithrombotic Therapy.

PubMed

D'Amore, Katrina; Traficante, David; McGovern, Terrance; Propersi, Marco; Barnes, Stacey

2017-11-01

Alveolar hemorrhage is a rare yet devastating clinical entity if not identified and treated aggressively. Exceedingly rare are the cases of anticoagulant-induced alveolar hemorrhage with very few cases described in the current literature. The nonspecific presentation of an alveolar hemorrhage makes its diagnosis and appropriate treatment difficult in the emergency department. We report a case of a patient on warfarin for atrial fibrillation who was initially misdiagnosed as having community-acquired pneumonia, but subsequently was identified to have a fatal alveolar hemorrhage.

Admissions with atrial fibrillation in a multiracial population in Kuala Lumpur, Malaysia.

PubMed

Freestone, B; Rajaratnam, R; Hussain, N; Lip, G Y H

2003-10-01

There are established differences in cardiovascular disease in different racial groups. Worldwide, the literature regarding the clinical epidemiology of atrial fibrillation in non-white populations is scarce. To document the prevalence of atrial fibrillation (AF) in the multiracial population of Malaysia, and to describe the clinical features and management of these patients. Busy city centre general hospital in Kuala Lumpur, Malaysia, over a 1-month period. One-thousand four hundred and thirty-five acute medical admissions, of whom 40 patients (2.8%) had AF. Of 1435 acute medical admissions to Kuala Lumpur General Hospital over the 4-week study period, 40 had AF (21 male, 19 female; mean age 65 years). Of these, 18 were Malay, 16 Chinese and six Indian. Nineteen patients had previously known AF (seven with paroxysmal AF) and 21 were newly diagnosed cases. The principal associated medical conditions were ischaemic heart disease (42.5%), hypertension (40%) and heart failure (40%). Dyspnoea was the commonest presentation, whilst stroke was the cause of presentation in only two patients. Investigations were under-utilised, with chest X-ray and echocardiography in only 62.5% of patients and thyroid function checked in 15%. Only 16% of those with previously diagnosed AF were on warfarin, with a further three on aspirin. Anticoagulant therapy was started in 13.5% of patients previously not on warfarin, and aspirin in 8%. Records of contraindications to warfarin were unreliable, being identified in only 25%. For those with known AF, 58% were on digoxin. For new onset AF, digoxin was again the most common rate-limiting treatment, initiated in 38%, whilst five patients with new onset AF were commenced on amiodarone. DC cardioversion was not used in any of the patients with new onset AF. Amongst acute medical admissions to a single centre in Malaysia the prevalence of AF was 2.8%. Consistent with previous similar surveys in mainly western (caucasian) populations, standard investigations in this Malaysian cohort were also inadequate and there was underuse of anticoagulation, medication for ventricular rate control and cardioversion to sinus rhythm.

In Potential Stroke Patients on Warfarin, the International Normalized Ratio Predicts Ischemia.

PubMed

Cao, Cathy; Martinelli, Ashley; Spoelhof, Brian; Llinas, Rafael H; Marsh, Elisabeth B

2017-01-01

Stroke can occur in patients on warfarin despite anticoagulation. Patients with a low international normalized ratio (INR) should theoretically be at greater risk for ischemia than those who are therapeutic. Therefore, INR may be able to indicate whether new neurological deficits are more likely strokes or stroke mimics in patients on warfarin. This study evaluates the association and predictive value of INR in determining the likelihood of ischemia. Patients were identified using the acute stroke registry at a Primary Stroke Center from January 2013 through December 2014. All adult patients undergoing evaluation for acute stroke with prior documented use of warfarin and an INR level at presentation were included. Data were collected regarding patient demographics, medical comorbidities, stroke severity, reason for anticoagulation, and laboratory studies including INR. Student t tests and χ2 analysis were used to evaluate factors associated with increased likelihood of ischemia (stroke or transient ischemic attack) versus mimic. Significant results were entered into a multivariable regression analysis. Sensitivity and specificity analyses were conducted to determine the predictive value of INR for ischemic risk. 116 patients were included; 46 were diagnosed with ischemia, 70 were diagnosed as mimics. 75% of patients were on warfarin for atrial fibrillation versus 25% for venous thrombosis. A statistically significant difference in mean INR for patients with ischemia (n = 46) versus mimics (n = 70) was observed (1.7 vs. 2.8; p < 0.001). In multivariable analysis, both sub-therapeutic INR (p < 0.001) and atrial fibrillation (p = 0.014) were predictors of ischemia. In patients with an INR ≥2, the predictive value of having a non-ischemic etiology was 79%. No patient with an INR of ≥3.6 was found to have ischemia. Sub-therapeutic INR and atrial fibrillation are strongly associated with ischemia in patients on warfarin presenting with acute neurologic symptoms. Ischemia is far less likely in patients with an INR of ≥2 and rare in those with an INR ≥3.6. This study shows that the INR value of a patient on warfarin can help stratify patients' risk for acute ischemic stroke and guide further neurologic imaging and workup. © 2017 The Author(s). Published by S. Karger AG, Basel.

Women hospitalized with atrial fibrillation: gender differences, trends and outcome from a 20-year registry in a Middle Eastern country (1991-2010).

PubMed

Salam, Amar M; AlBinali, Hajar A; Al-Mulla, Abdul Wahid; Asaad, Nidal; Singh, Rajvir; Al-Qahtani, Awad; Al Suwaidi, Jassim

2013-09-30

Most of the published research on atrial fibrillation (AF) is limited to studies in the developed world and included mainly Caucasian patients. Data about women with AF among other ethnicities is very limited. The aim of this study was to compare the clinical characteristics, treatment and outcome of women to men hospitalized with AF in a middle-eastern country. Retrospective analysis of prospective registry of all patients hospitalized with AF in Qatar from 1991 through 2010 was made. Clinical characteristics, management, and outcomes of AF patients were compared according to gender. During the 20-years period; 1417 women and 2432 men were hospitalized for AF. Women were 5 years older and more likely to have diabetes mellitus, hypertension, and chronic renal impairment and were also less likely to be current smokers and to have ischemic heart disease and impaired left ventricular function when compared to men. There was no gender preference in the use of anticoagulation. The prevalence of concomitant ischemic heart disease and hypertension increased, while the prevalence of valvular heart disease and heart failure decreased among patients hospitalized with AF over the study period. In-hospital mortality and stroke rates were comparable between the two groups. Women hospitalized with atrial fibrillation were older in age and had higher prevalence of co-morbid cardiovascular risk factors compared to men whereas, mortality and stroke rates were comparable. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Safety and Efficacy of Switching Anticoagulation to Aspirin Three Months after Successful Radiofrequency Catheter Ablation of Atrial Fibrillation

PubMed Central

Uhm, Jae-Sun; Won, Hoyoun; Joung, Boyoung; Nam, Gi-Byoung; Choi, Kee-Joon; Lee, Moon-Hyoung; Kim, You-Ho

2014-01-01

Purpose Although current guidelines recommend continuing the same antithrombotic strategy regardless of rhythm control after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), anticoagulation has a risk of major bleeding. We evaluated the safety of switching warfarin to aspirin in patients with successful AF ablation. Materials and Methods Among 721 patients who underwent RFCA of AF, 608 patients (age, 57.3±10.9 years; 77.0% male, 75.5% paroxysmal AF) who had no evidence of AF recurrence at 3 months post-RFCA were included. We compared the thromboembolic and hemorrhagic events in patients for whom warfarin was switched to aspirin (ASA group; n=296) and patients who were kept on warfarin therapy (W group; n=312). Results There were no significant differences in CHA2DS2-VASc or HAS-BLED scores between the groups. In 30 patients in the ASA group and 37 patients in W group, AF recurred and warfarin was restarted or maintained during the 18.0±12.2 months of follow-up. There were no significant differences in thromboembolic (0.3% vs. 1.0%, p=0.342) and major bleeding incidences (0.7% vs. 0.6%, p=0.958) between ASA and W groups during the follow-up period. In the 259 patients with a CHA2DS2-VASc score ≥2, there were no significant differences in thromboembolism (0.8% and 2.2%, p=0.380) or major bleeding incidences (0.8% and 1.4%, p=0.640) between ASA and W groups. Conclusion Switching warfarin to aspirin 3 months after successful RFCA of AF could be as safe and efficacious as long-term anticoagulation even in patients with CHA2DS2-VASc score ≥2. However, strict rhythm monitoring cannot be overemphasized. PMID:25048480

Balancing between bleeding and thromboembolism after percutaneous coronary intervention in patients with atrial fibrillation. Could triple anticoagulant therapy be a solution?

PubMed

Dąbrowska, Magdalena; Ochała, Andrzej; Cybulski, Wiesław; Tendera, Michał

2013-01-01

Atrial fibrillation (AF) has nowadays become a common disease as it comes along with medical procedures propagation in the ageing population with coexistent diseases. Hence a need for use of combined anticoagulant and antithrombotic therapy has arisen. According to the 2010 ESC guidelines on myocardial revascularization, short-term triple antithrombotic therapy after percutaneous coronary intervention (PCI) should be given if compelling indications exist. To assess bleeding and thromboembolic events depending on the antithrombotic regimen in short- and long-term follow-up in patients with AF after PCI with stent implantation. A 12-month prospective, non-randomized registry was conducted in the 3(rd) Department of Cardiology in the Upper Silesian Medical Center in Katowice from October 2008 to April 2011. One hundred and four patients in two groups - on triple therapy (TT; aspirin + clopidogrel + vitamin K antagonists (VKA; warfarin or acenocoumarol) n = 44) and on dual therapy (DT; aspirin + clopidogrel; n = 60) - were assessed 30 days and 12 months after angioplasty. All bleeding events occurred more often in the triple anticoagulated group in 30 days (TT 20.5% vs. DT 6.7%; p = 0.03) and after 12 months (TT 38.9% vs. DT 17.2%, p = 0.09). The difference in major bleeding events was not significant after 30 days (TT 9.1% vs. DT 3.3%; p = NS) or 12 months (TT 11.1% vs. DT 6.9%; p = NS). Thromboembolic events after 30 days (DT 5.0% vs. TT 2.3%) and 12 months (TT 11.1% vs. DT 3.4%) were comparable. The percentage of deaths after 30 days (DT 1.7% vs. TT 0.0%, p = NS) increased after 12 months (DT 13.8% vs. TT 0.0%, p = 0.09). Significantly higher risk of bleeding on TT becomes blurred by a tendency to increased mortality in patients on DT.

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.

Emerging therapeutic uses of direct-acting oral anticoagulants: An evidence-based perspective.

PubMed

Raschi, Emanuel; Bianchin, Matteo; De Ponti, Roberto; De Ponti, Fabrizio; Ageno, Walter

2017-06-01

Direct-acting oral anticoagulants (DOACs) were claimed to cause a potential paradigm shift in the therapeutic scenario of patients requiring short- and long-term anticoagulation, by virtue of their pharmacological properties, perceived as innovative. The evidence gathered so far (from pre-approval pivotal trials to real-world post-marketing observational data) consistently confirmed that DOACs are overall comparable to vitamin-K antagonists (VKAs) in terms of safety, efficacy and effectiveness and unequivocally documented a consistent and clinically relevant reduced risk of intracranial bleeding in the settings of non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). Interestingly, two parallel paths can be identified in the current research scenario: A) in the aforementioned consolidated therapeutic indications, an innovative approach is directed towards tailored treatment strategies, to identify patients most likely to benefit from one of the different anticoagulant drugs, in particular subpopulations at increased risk of adverse events (e.g., bleeding); B) in unconventional settings, DOACs are gaining interest for potential use in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk-benefit profile of DOACs, as compared to VKAs or heparins, is less defined. The aim of this review is to critically assess the body of evidence underlying emerging therapeutic uses of DOACs (e.g., heparin-induced thrombocytopenia, anti-phospholipid antibody syndrome), including evolving issues in special populations (e.g., patients with VTE and cancer or cirrhosis). This will be achieved by analyzing the strength (i.e., systematic reviews, randomized clinical trials, observational studies, case report/series) and consistency (i.e., concordance) of both published and unpublished evidence registered in major public repositories. Copyright © 2017 Elsevier Ltd. All rights reserved.

Brain and kidney, victims of atrial microembolism in elderly hospitalized patients? Data from the REPOSI study.

PubMed

Corrao, S; Argano, C; Nobili, A; Marcucci, M; Djade, C D; Tettamanti, M; Pasina, L; Franchi, C; Marengoni, A; Salerno, F; Violi, F; Mannucci, P M; Perticone, F

2015-05-01

It is well known that atrial fibrillation (AF) and chronic kidney disease (CKD) are associated with a higher risk of stroke, and new evidence links AF to cognitive impairment, independently from an overt stroke (CI). Our aim was to investigate, assuming an underlying role of atrial microembolism, the impact of CI and CKD in elderly hospitalized patients with AF. We retrospectively analyzed the data collected on elderly patients in 66 Italian hospitals, in the frame of the REPOSI project. We analyzed the clinical characteristics of patients with AF and different degrees of CI. Multivariate logistic analysis was used to explore the relationship between variables and mortality. Among the 1384 patients enrolled, 321 had AF. Patients with AF were older, had worse CI and disability and higher rates of stroke, hypertension, heart failure, and CKD, and less than 50% were on anticoagulant therapy. Among patients with AF, those with worse CI and those with lower estimated glomerular filtration rate (eGFR) had a higher mortality risk (odds ratio 1.13, p=0.006). Higher disability levels, older age, higher systolic blood pressure, and higher eGFR were related to lower probability of oral anticoagulant prescription. Lower mortality rates were found in patients on oral anticoagulant therapy. Elderly hospitalized patients with AF are more likely affected by CI and CKD, two conditions that expose them to a higher mortality risk. Oral anticoagulant therapy, still underused and not optimally enforced, may afford protection from thromboembolic episodes that probably concur to the high mortality. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Visual Aid Tool to Improve Decision Making in Anticoagulation for Stroke Prevention.

PubMed

Saposnik, Gustavo; Joundi, Raed A

2016-10-01

The management of stroke prevention among patients with atrial fibrillation (AF) has changed in the last few years. Despite the benefits of new oral anticoagulants (NOACs), decisions about the optimal agent remain a challenge. We provide a visual aid tool to guide clinicians and patients in the decision process of selecting oral anticoagulants for stroke prevention. We created visual plots representing benefits of warfarin versus NOACs from a meta-analysis comprising 58,541 participants. Visual plots (Cates plots) were created using software available at nntonline.net. The primary outcome was stroke or systemic embolism during the study period. In the chosen meta-analysis, 29,312 participants received a NOAC and 29,229 participants received warfarin. For every 1000 patients with AF, 38 would have a stroke or systemic embolic event in the warfarin group compared to 31 in the NOAC group (RR .81; 95% CI .73-.91). Fifteen patients would develop an intracranial hemorrhage in the warfarin group compared to 7 in the NOAC group (RR .48; 95% CI .39-.59). Conversely, 25 patients would develop gastrointestinal bleeding in the NOAC group compared to 20 in the warfarin group (RR 1.25; 95% CI 1.01-1.55). For every 1000 treated individuals with AF, NOACs would prevent stroke or systemic embolism in 7 additional patients and cerebral hemorrhage in 8 additional patients compared to warfarin. On the other hand, 5 more patients would develop gastrointestinal bleeding with NOACs compared to warfarin. These data are visually shown in Cates plots, facilitating conversations with patients regarding anticoagulation decisions. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Cost-Effectiveness Analysis of Apixaban, Dabigatran, Rivaroxaban, and Warfarin for Stroke Prevention in Atrial Fibrillation in Taiwan.

PubMed

Liu, Chieh-Yu; Chen, Hui-Chun

2017-03-01

The aim of this study was to evaluate the cost effectiveness of novel oral anticoagulants (NOACs) for stroke prevention among atrial fibrillation (AF) patients by incorporating Taiwanese demographic information derived from a population-based database, the National Health Insurance Research Database (NHIRD), into cost-effectiveness analysis. From 1 January to 31 December 2012, 98,213 AF patients were selected from the NHIRD database. A Markov model was constructed that combined published secondary data with the Taiwan NHIRD to compare the cost and incremental cost effectiveness of apixaban 5 mg twice daily, dabigatran 110 or 150 mg twice daily, rivaroxaban 20 mg once daily, and warfarin. The lifetime costs of warfarin, dabigatran 110 mg, dabigatran 150 mg, rivaroxaban 20 mg, and apixaban 5 mg were US$10,660, US$13,693, US$13,426, US$13,455, US$15,965, respectively. Apixaban resulted in an incremental cost effectiveness of US$39,351, US$27,039, US$41,298, and US$48,896 per quality-adjusted life-year (QALY) compared with warfarin, dabigatran 110 mg, dabigatran 150 mg, and rivaroxaban 20 mg, respectively. In Monte-Carlo analyses, apixaban 5 mg, rivaroxaban 20 mg, warfarin, and dabigatran 110 mg were cost effective in 83, 10.4, 7, and 0.8%, respectively, of the simulations using a willingness-to-pay (WTP) threshold of US$50,000 per QALY. Apixaban was more cost effective than warfarin, dabigatran, and rivaroxaban for stroke prevention in patients with AF. Among the anticoagulant therapies, the WTP threshold of apixaban was about US$50,000 per QALY gained. These cost-effectiveness estimations provide useful information to aid clinical decision making in stroke prevention for AF patients.

Early introduction of direct oral anticoagulants in cardioembolic stroke patients with non-valvular atrial fibrillation.

PubMed

Cappellari, Manuel; Carletti, Monica; Danese, Alessandra; Bovi, Paolo

2016-10-01

Direct oral anticoagulants (DOACs) are superior to warfarin in reduction of the intracranial bleeding risk. The aim of the present study was to assess whether early DOAC introduction (1-3 days after onset) in stroke patients with non-valvular atrial fibrillation (nVAF) may be safe and effective, compared with DOAC introduction after 4-7 days. We conducted a prospective analysis based on data collected from 147 consecutive nVAF patients who started DOAC within 7 days after stroke onset. In all patients, we performed pre-DOAC CT scan 24-36 h after onset and follow-up CT scan at 7 days after DOAC introduction. Outcome measures were post-DOAC intracranial bleeding (new any intracerebral hemorrhage (ICH) in patients with pre-DOAC infarct without hemorrhagic transformation (HT) or expansion of ICH in patients with pre-DOAC infarct with asymptomatic HT) and post-DOAC recurrent ischemic stroke (any new ischemic infarct) on follow-up CT scan. 97 patients started DOAC after 1-3 days and 50 patients started DOAC after 4-7 days. On pre-DOAC CT scan, 132 patients had an infarct without HT and 15 an infarct with asymptomatic HT. On follow-up CT scan, new any ICH was noted in seven patients (asymptomatic in 6) and asymptomatic expansion of ICH in one patient. We found no association between early DOAC introduction and intracranial bleeding. Large infarct remained the only independent predictor of post-DOAC intracranial bleeding. No patients suffered recurrent ischemic stroke after DOAC introduction. Early DOAC introduction might be safe in carefully selected patients with nVAF who experience small- and medium-sized cardioembolic ischemic strokes. Further investigation will be needed.

Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk undergoing coronary stenting: design of the MUSICA-2 randomized trial.

PubMed

Sambola, Antonia; Montoro, J Bruno; Del Blanco, Bruno García; Llavero, Nadia; Barrabés, José A; Alfonso, Fernando; Bueno, Héctor; Cequier, Angel; Serra, Antonio; Zueco, Javier; Sabaté, Manel; Rodríguez-Leor, Oriol; García-Dorado, David

2013-10-01

Oral anticoagulation (OAC) is the recommended therapy for patients with atrial fibrillation (AF) because it reduces the risk of stroke and other thromboembolic events. Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention and stenting (PCI-S). In patients with AF requiring PCI-S, the association of DAPT and OAC carries an increased risk of bleeding, whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events. The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy (TT) in patients with nonvalvular AF at low-to-moderate risk of stroke (CHADS2 score ≤2) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications. The MUSICA-2 is a multicenter, open-label randomized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S. The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events: death, myocardial infarction, stent thrombosis, or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients. The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications. © 2013.

Comparison of the Effectiveness and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Newly Diagnosed Atrial Fibrillation.

PubMed

Hernandez, Inmaculada; Zhang, Yuting; Saba, Samir

2017-11-15

No studies have performed direct pairwise comparisons of the effectiveness and safety of warfarin and the new oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban. Using 2013 to 2014 claims from a 5% random sample of Medicare beneficiaries, we identified patients newly diagnosed with atrial fibrillation who initiated apixaban, dabigatran, rivaroxaban, warfarin, or no oral anticoagulation therapy in 2013 to 2014. Outcomes included the composite of ischemic stroke, systemic embolism (SE) and death, any bleeding event, gastrointestinal bleeding, intracranial bleeding, and treatment persistence. We constructed Cox proportional hazard models to compare outcomes between each pair of treatment groups. The composite risk of ischemic stroke, SE, and death was lower for NOACs than for warfarin: hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76 to 0.98 for apixaban; 0.73, 95% CI 0.63 to 0.86 for dabigatran; and 0.82, 95% CI 0.75 to 0.89 for rivaroxaban, all compared with warfarin. There were no differences in effectiveness across NOACs. The risk of any bleeding was lower with apixaban than with warfarin, but higher with rivaroxaban than with warfarin. Apixaban (HR 0.69, 95% CI 0.60 to 0.79) and dabigatran (HR 0.79, 95% CI 0.69 to 0.92) were associated with lower bleeding risk than rivaroxaban. Treatment persistence was highest for apixaban (82%), and lowest for dabigatran and warfarin (64%) (p value <0.001). Compared with warfarin, NOACs are more effective in preventing stroke but their risk of bleeding varies, with rivaroxaban having higher risk than warfarin. Altogether, apixaban had the most favorable effectiveness, safety, and persistence profile. Copyright © 2017 Elsevier Inc. All rights reserved.

Atrial fibrillation, CHA2DS2-VASc score, antithrombotics and risk of traffic accidents: A population-based cohort study.

PubMed

Lai, Hui-Chin; Chien, Wu-Chien; Chung, Chi-Hsiang; Lee, Wen-Lieng; Wang, Kuo-Yang; Wu, Tsu-Juey; Liu, Chia-Ning; Liu, Tsun-Jui

2015-10-15

Traffic accidents account for a substantial proportion of premature disabilities and deaths. Whether atrial fibrillation (AF) provokes while antithrombotics prevent from such events remains un-investigated. All patients ≥40years with newly diagnosed AF in 2005 were scrutinized from the "Longitudinal Health Insurance Database 2005" (1 million beneficiaries) of Taiwan's National Health Insurance Institute as the AF group. Four-fold number of age-, gender-, and comorbidity-matched patients but without AF served as the Non-AF controls. Patients were followed till occurrence of hospitalization-requiring traffic injury, death, withdrawal from insurance, or the end of 2010. Cumulative incidence of traffic accidents was compared between groups, and predictors and preventive role of antithrombotics for these accidents were identified by Cox regression analysis. Within a mean follow-up of 4.3years, traffic injury occurred significantly more often in patients with AF (N=1724) than those without it (N=6896) (5.4 vs. 4.9 per 1000 person-years, log-rank p=0.012, HR 1.110, 95% CI 1.013-1.572). Cox models identified age ≧65years, hypertension, coronary artery disease, stroke, liver cirrhosis and CHADS2VASC score≧1 as risk factors for traffic injury in AF patients, whereas oral anticoagulants (HR 0.576, 95% CI 0.285-0.791, p=0.002) used in patients with CHADS2VASC score ≧1 but not antiplatelet therapy (p=0.197) as negative predictors. Patients with AF are more vulnerable to traffic accidents especially when with higher CHADS2VASC scores and other comorbidities. This tendency to traffic accidents, however, could be ameliorated by oral anticoagulation in specialized cases but not by antiplatelet therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Benefit of Anticoagulation Therapy in Hyperthyroidism-Related Atrial Fibrillation.

PubMed

Chan, Pak-Hei; Hai, Jojo; Yeung, Chun-Yip; Lip, Gregory Y H; Lam, Karen Siu-Ling; Tse, Hung-Fat; Siu, Chung-Wah

2015-08-01

Existing data on the risk of ischemic stroke in hyperthyroidism-related atrial fibrillation (AF) and the impact of long-term anticoagulation in these patients, particularly those with self-limiting AF, remain inconclusive. Risk of stroke in hyperthyroidism-related AF is the same as nonhyperthyroid counterparts. This was a single-center observational study of 9727 Chinese patients with nonvalvular AF from July 1997 to December 2011. Patients with AF diagnosed concomitantly with hyperthyroidism were identified. Primary and secondary endpoints were defined as hospitalization with ischemic stroke and intracranial hemorrhage in the first 2 years. Patient characteristics, duration of AF, and choice of antithrombotic therapy were recorded. Self-limiting AF was defined as <7 days' duration. Out of 9727 patients, 642 (6.6%) had concomitant hyperthyroidism and AF at diagnosis. For stroke prevention, 136 and 243 patients (21.1% and 37.9%) were prescribed warfarin and aspirin, respectively, whereas the remaining patients (41.0%) received no therapy. Ischemic stroke occurred in 50 patients (7.8%), and no patient developed hemorrhagic stroke. Patients with CHA2 DS2 -VASc of 0 did not develop stroke. Warfarin effectively reduced the incidence of stroke compared with aspirin or no therapy in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF, but not in those with self-limiting AF or CHA2 DS2 -VASc of 0. Presence of hyperthyroidism did not confer additional risk of ischemic stroke compared with nonhyperthyroid AF. Patients with hyperthyroidism-related AF are at high risk of stroke (3.9% per year). Warfarin confers stroke prevention in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF. Overall stroke risk was lower in hyperthyroid non-self-limiting AF patients compared with nonhyperthyroid counterparts. © 2015 Wiley Periodicals, Inc.