Do socioeconomic disparities affect accessing and keeping antihypertensive drug therapy? Evidence from an Italian population-based study.

PubMed

Corrao, G; Zambon, A; Parodi, A; Mezzanzanica, M; Merlino, L; Cesana, G; Mancia, G

2009-04-01

We conducted this population-based cohort study by linking several databases to explore the role of socioeconomic position for accessing and keeping antihypertensive drug therapy. A total of 71 469 patients, residents in the city of Milan (Italy) aged 40-80 years, who received an antihypertensive drug during 1999-2002 were followed for 1 year starting from the first dispensation. Socioeconomic position and drug prescriptions were respectively obtained from tax registry and outpatient prescription database. The effect of socioeconomic characteristics on standardized incidence rate (SIR) of new users of antihypertensive agents, odds ratio (OR) of using combined antihypertensive agents and non-antihypertensive drugs and hazard ratio (HR) of discontinuing antihypertensive therapy were estimated after adjustment for potential confounders. SIRs were 3.7 and 4.2 per 1000 person-months among persons at the lowest and intermediate income, respectively, and 2.4 and 3.0 among immigrants and Italians, respectively. Compared to persons at the highest income, those at the lowest income had increased chances of starting with combined antihypertensive drugs (OR: 1.1; 95% confidence intervals (CIs): 1.0, 1.2), and of using drugs for heart failure (OR:1.5; CIs:1.3, 1.6) and diabetes (OR: 1.7; CIs: 1.6, 1.9). Compared with Italians, non-western immigrants had increased chances of starting with combined antihypertensive agents (OR: 1.2; CIs: 1.0, 1.3), of using drugs for heart failure (OR: 1.2; CIs: 1.0, 1.4) and for diabetes (OR: 1.8; CIs: 1.6, 2.1), and of interrupting antihypertensive therapy (HR: 1.1; 95% CIs: 1.0, 1.2). Despite the universal health coverage of the Italian National Health Service (NHS), social disparities affect accessing and keeping antihypertensive therapy.

Effects of intense aerobic exercise and/or antihypertensive medication in individuals with metabolic syndrome.

PubMed

Ramirez-Jimenez, M; Morales-Palomo, F; Ortega, J F; Mora-Rodriguez, R

2018-05-17

We studied the blood pressure lowering effects of a bout of exercise and/or antihypertensive medicine with the goal of studying if exercise could substitute or enhance pharmacologic hypertension treatment. Twenty-three hypertensive metabolic syndrome patients chronically medicated with angiotensin II receptor 1 blockade antihypertensive medicine underwent 24-hr monitoring in four separated days in a randomized order; a) after taking their habitual dose of antihypertensive medicine (AHM trial), b) substituting their medicine by placebo medicine (PLAC trial), c) placebo medicine with a morning bout of intense aerobic exercise (PLAC+EXER trial) and d) combining the exercise and antihypertensive medicine (AHM+EXER trial). We found that in trials with AHM subjects had lower plasma aldosterone/renin activity ratio evidencing treatment compliance. Before exercise, the trials with AHM displayed lower systolic (130±16 vs 133±15 mmHg; P=0.018) and mean blood pressures (94±11 vs 96±10 mmHg; P=0.036) than trials with placebo medication. Acutely (i.e., 30 min after treatments) combining AHM+EXER lowered systolic blood pressure (SBP) below the effects of PLAC+EXER (-8.1±1.6 vs -4.9±1.5 mmHg; P=0.015). Twenty-four hour monitoring revealed no differences among trials in body motion. However, PLAC+EXER and AHM lowered SBP below PLAC during the first 10 hours, time at which PLAC+EXER effects faded out (i.e., at 19 PM). Adding exercise to medication (i.e., AHM+EXER) resulted in longer reductions in SBP than with exercise alone (PLAC+EXER). In summary, one bout of intense aerobic exercise in the morning cannot substitute the long-lasting effects of antihypertensive medicine in lowering blood pressure, but their combination is superior to exercise alone. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial

PubMed Central

Agarwal, Rajiv; Sinha, Arjun D.; Pappas, Maria K.; Abraham, Terri N.; Tegegne, Getachew G.

2014-01-01

Background The purpose of this study was to determine among maintenance hemodialysis patients with echocardiographic left ventricular hypertrophy and hypertension whether in comparison with a β-blocker-based antihypertensive therapy, an angiotensin converting enzyme-inhibitor-based antihypertensive therapy causes a greater regression of left ventricular hypertrophy. Methods Subjects were randomly assigned to either open-label lisinopril (n = 100) or atenolol (n = 100) each administered three times per week after dialysis. Monthly monitored home blood pressure (BP) was controlled to <140/90 mmHg with medications, dry weight adjustment and sodium restriction. The primary outcome was the change in left ventricular mass index (LVMI) from baseline to 12 months. Results At baseline, 44-h ambulatory BP was similar in the atenolol (151.5/87.1 mmHg) and lisinopril groups, and improved similarly over time in both groups. However, monthly measured home BP was consistently higher in the lisinopril group despite the need for both a greater number of antihypertensive agents and a greater reduction in dry weight. An independent data safety monitoring board recommended termination because of cardiovascular safety. Serious cardiovascular events in the atenolol group occurred in 16 subjects, who had 20 events, and in the lisinopril group in 28 subjects, who had 43 events {incidence rate ratio (IRR) 2.36 [95% confidence interval (95% CI) 1.36–4.23, P = 0.001]}. Combined serious adverse events of myocardial infarction, stroke and hospitalization for heart failure or cardiovascular death in the atenolol group occurred in 10 subjects, who had 11 events and in the lisinopril group in 17 subjects, who had 23 events (IRR 2.29, P = 0.021). Hospitalizations for heart failure were worse in the lisinopril group (IRR 3.13, P = 0.021). All-cause hospitalizations were higher in the lisinopril group [IRR 1.61 (95% CI 1.18–2.19, P = 0.002)]. LVMI improved with time; no difference between drugs was noted. Conclusions Among maintenance dialysis patients with hypertension and left ventricular hypertrophy, atenolol-based antihypertensive therapy may be superior to lisinopril-based therapy in preventing cardiovascular morbidity and all-cause hospitalizations. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number: NCT00582114) PMID:24398888

Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

PubMed Central

Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A.

2017-01-01

Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general. PMID:26514749

The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC Trial): study protocol for a randomized controlled trial.

PubMed

Karamat, Fares A; Horjus, Deborah L; Haan, Yentl C; van der Woude, Lisa; Oudman, Inge; van Montfrans, Gert A; Clark, Joseph F; Brewster, Lizzy M

2015-02-22

Despite adequate treatment, up to 30% of treated antihypertensive patients with primary, uncomplicated hypertension remain uncontrolled. We proposed that high intracellular activity of the ATP regenerating enzyme creatine kinase (CK) increases pressor responses and hypertension risk. In line with this, we found that plasma CK activity after rest, a surrogate measure of tissue activity, is the main predictor of blood pressure levels and failure of antihypertensive therapy in the general population. In addition, the creatine analog and competitive oral creatine kinase inhibitor beta-guanidinopropionic acid effectively and safely reduced blood pressure in the spontaneously hypertensive rat. However, to our knowledge there are no human data on the safety of oral supplementation with this substance. Therefore, we will assess the tolerability of beta-guanidinopropionic acid in men, compared to creatine and placebo. This is a randomized, active and placebo controlled, triple blind, double dummy, single center clinical intervention trial in 24 healthy male volunteers, 18 to 50 years old, recruited in the Netherlands. The intervention consists of one week of daily oral administration of beta-guanidinopropionic acid 100 mg, creatine 5 gram, or placebo. The primary outcome is the tolerability of beta-guanidinopropionic acid as a descriptive measure, in an intent-to-treat analysis. Other outcomes include the placebo-adjusted differences with baseline in biochemical and hemodynamic parameters, including plasma markers of muscle tissue damage, urine sodium excretion, resting sitting systolic and diastolic brachial blood pressure, supine systolic and diastolic central blood pressure, pulse wave velocity and augmentation index, heart rate, cardiac contractility, cardiac output, and total peripheral resistance. There is an unfulfilled need for new conservative options to treat resistant hypertension. This study will provide first-in-men data on creatine kinase inhibition as a potential new class of antihypertensive drugs. The Netherlands National Trial Register Trialregister.nl (identifier NTR 4444) , registered 9 March 2014.

The effect of antihypertensive treatment on the incidence of stroke and cognitive decline in the elderly: a meta-analysis.

PubMed

Parsons, Christine; Murad, Mohammad Hassan; Andersen, Stuart; Mookadam, Farouk; Labonte, Helene

2016-03-01

To evaluate the effectiveness of antihypertensives in reducing neurocognitive outcomes in elderly patients. We conducted a systematic literature search of randomized trials in which hypertensive patients with a mean age ≥65 years received antihypertensive or control treatment. Outcomes were stroke, transient ischemic attack, cognitive decline and dementia. We included 14 trials for meta-analysis. Compared to placebo, antihypertensive treatment reduced the risk of stroke (RR: 0.67 [95% CI: 0.57-0.79]). Reduced risk was significant for transient ischemic attack, fatal stroke, nonfatal stroke and total stroke. There were insufficient data to compare individual agents. Antihypertensive treatment is associated with a significant reduction in stroke in elderly individuals. Reductions in dementia and cognitive decline were not significant; however, there was short follow-up. Comparative effectiveness evidence is limited.

Zhen Gan Xi Feng Decoction, a Traditional Chinese Herbal Formula, for the Treatment of Essential Hypertension: A Systematic Review of Randomized Controlled Trials

PubMed Central

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use. PMID:23573163

Long-term organ protection by doxazosin and/or quinapril as antihypertensive therapy.

PubMed

Gallego-Delgado, Julio; Lazaro, Alberto; Gomez-Garre, Dulcenombre; Osende, Julio I; Gonzalez-Rubio, Maria L; Herraiz, Marta; Manzarbeitia, Félix; Fortes, José; Fernandez-Cruz, Arturo; Egido, Jesús

2006-01-01

Even with optimal blood pressure control, organ protection may also depend on the selected therapeutic regime. Angiotensin-converting enzyme inhibitors have been shown to provide excellent organ protection in hypertension, and may show dose-dependent protective effects. Adrenergic alpha blockers have been associated with an increased rate of heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and Vasodilator-Heart Failure Trial (V-HeFT). This has been related to a proapoptotic effect of this drug in cardiomyocytes. Our purpose is to compare the heart and renal protection of a high quinapril dose, with a combined low quinapril dose plus doxazosin, in an animal model of chronic hypertension. Uninephrectomized spontaneously hypertensive 12-week-old rats were treated for 36 weeks with either quinapril or a combination of doxazosin plus a low quinapril dose. Tight blood pressure control was achieved with both treatments. Renal and cardiac protection was assessed by different parameters, and cardiac apoptosis was evaluated by active caspase-3, apoptotic protein and heat shock protein levels. Untreated hypertensive and normotensive rats were included as controls. Both treatments showed significant heart and renal protection compared with untreated animals. Both therapeutic regimes showed similar protection in renal and cardiac pathology, coronary media fibrosis, myocardial apoptosis and cardiac index. Proteinuria and left ventricular hypertrophy regression were significantly lower in the quinapril group compared with the combined treatment group. Blood pressure control with a high quinapril dose provided higher organ protection than a combined therapy with a lower quinapril dose. This effect was not due to a deleterious effect of doxazosin.

Health effects of hawthorn.

PubMed

Dahmer, Stephen; Scott, Emilie

2010-02-15

Hawthorn medicinal extract has long been a favored herbal remedy in Europe. The active components of this slow-acting cardiotonic agent are thought to be flavonoids and oligomeric procyanidins. The most studied hawthorn extracts are WS 1442 and LI 132. Reviews of placebo- controlled trials have reported both subjective and objective improvement in patients with mild forms of heart failure (New York Heart Association classes I through III). Other studies of hawthorn in patients with heart failure have revealed improvement in clinical symptoms, pressure-heart rate product, left ventricular ejection fraction, and patients' subjective sense of well-being. However, there is no evidence of a notable reduction in mortality or sudden death. Hawthorn is well tolerated; the most common adverse effects are vertigo and dizziness. Theoretic interactions exist with antiarrhythmics, antihypertensives, digoxin, and antihyperlipidemic agents. Proven conventional therapies for heart failure are still recommended until the safety and effectiveness of hawthorn has been proven in long-term studies.

Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial.

PubMed

Azizi, Michel; Pereira, Helena; Hamdidouche, Idir; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Mounier-Véhier, Claire; Courand, Pierre-Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Girerd, Xavier; Michel Halimi, Jean; Zannad, Faiez; Ormezzano, Olivier; Vaïsse, Bernard; Herpin, Daniel; Ribstein, Jean; Chamontin, Bernard; Mourad, Jean-Jacques; Ferrari, Emile; Plouin, Pierre-François; Jullien, Vincent; Sapoval, Marc; Chatellier, Gilles

2016-09-20

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control. One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients. The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients. In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777. © 2016 American Heart Association, Inc.

Potentially Inappropriate Antihypertensive Prescriptions to Elderly Patients: Results of a Prospective, Observational Study.

PubMed

Márquez, Paola H Ponte; Torres, Olga H; San-José, Anonio; Vidal, Xavier; Agustí, Antonia; Formiga, Francesc; López-Soto, Alfonso; Ramírez-Duque, Nieves; Fernández-Moyano, Antonio; Garcia-Moreno, Juana; Arroyo, Juan A; Ruiz, Domingo

2017-06-01

Previous studies of antihypertensive treatment of older patients have focused on blood pressure control, cardiovascular risk or adherence, whereas data on inappropriate antihypertensive prescriptions to older patients are scarce. The aim of the study was to assess inappropriate antihypertensive prescriptions to older patients. An observational, prospective multicentric study was conducted to assess potentially inappropriate prescription of antihypertensive drugs, in patients aged 75 years and older with arterial hypertension (HTN), in the month prior to hospital admission, using four instruments: Beers, Screening Tool of Older Person's Prescriptions (STOPP), Screening Tool to Alert Doctors to the Right Treatment (START) and Assessing Care of Vulnerable Elders 3 (ACOVE-3). Primary care and hospital electronic records were reviewed for HTN diagnoses, antihypertensive treatment and blood pressure readings. Of 672 patients, 532 (median age 85 years, 56% female) had HTN. 21.6% received antihypertensive monotherapy, 4.7% received no hypertensive treatment, and the remainder received a combination of antihypertensive therapies. The most frequently prescribed antihypertensive drugs were diuretics (53.5%), angiotensin-converting enzyme inhibitors (ACEIs) (41%), calcium antagonists (32.2%), angiotensin receptor blockers (29.7%) and beta-blockers (29.7%). Potentially inappropriate prescription was observed in 51.3% of patients (27.8% overprescription and 35% underprescription). The most frequent inappropriately prescribed drugs were calcium antagonists (overprescribed), ACEIs and beta-blockers (underprescribed). ACEI and beta-blocker underprescriptions were independently associated with heart failure admissions [beta-blockers odds ratio (OR) 0.53, 95% confidence interval (CI) 0.39-0.71, p < 0.001; ACEIs OR 0.50, 95% CI 0.36-0.70, p < 0.001]. Potentially inappropriate prescription was detected in more than half of patients receiving antihypertensive treatment. Underprescription was more frequent than overprescription. ACEIs and beta-blockers were frequently underprescribed and were associated with heart failure admissions.

The effect of how outcomes are framed on decisions about whether to take antihypertensive medication: a randomized trial.

PubMed

Carling, Cheryl L L; Kristoffersen, Doris Tove; Oxman, Andrew D; Flottorp, Signe; Fretheim, Atle; Schünemann, Holger J; Akl, Elie A; Herrin, Jeph; MacKenzie, Thomas D; Montori, Victor M

2010-03-01

We conducted an Internet-based randomized trial comparing three valence framing presentations of the benefits of antihypertensive medication in preventing cardiovascular disease (CVD) for people with newly diagnosed hypertension to determine which framing presentation resulted in choices most consistent with participants' values. In this second in a series of televised trials in cooperation with the Norwegian Broadcasting Company, adult volunteers rated the relative importance of the consequences of taking antihypertensive medication using visual analogue scales (VAS). Participants viewed information (or no information) to which they were randomized and decided whether or not to take medication. We compared positive framing over 10 years (the number escaping CVD per 1000); negative framing over 10 years (the number that will have CVD) and negative framing per year over 10 years of the effects of antihypertensive medication on the 10-year risk for CVD for a 40 year-old man with newly diagnosed hypertension without other risk factors. Finally, all participants were shown all presentations and detailed patient information about hypertension and were asked to decide again. We calculated a relative importance score (RIS) by subtracting the VAS-scores for the undesirable consequences of antihypertensive medication from the VAS-score for the benefit of CVD risk reduction. We used logistic regression to determine the association between participants' RIS and their choice. 1,528 participants completed the study. The statistically significant differences between the groups in the likelihood of choosing to take antihypertensive medication in relation to different values (RIS) increased as the RIS increased. Positively framed information lead to decisions most consistent with those made by everyone for the second, more fully informed decision. There was a statistically significant decrease in deciding to take antihypertensives on the second decision, both within groups and overall. For decisions about taking antihypertensive medication for people with a relatively low baseline risk of CVD (70 per 1000 over 10 years), both positive and negative framing resulted in significantly more people deciding to take medication compared to what participants decided after being shown all three of the presentations. International Standard Randomised Controlled Trial Number Register ISRCTN 33771631.

INtensive versus Standard Ambulatory Blood Pressure Lowering to Prevent Functional DeclINe In The ElderlY (INFINITY)

PubMed Central

White, William B.; Marfatia, Ravi; Schmidt, Julia; Wakefield, Dorothy B.; Kaplan, Richard F.; Bohannon, Richard W.; Hall, Charles B.; Guttmann, Charles R.; Moscufo, Nicola; Fellows, Douglas; Wolfson, Leslie

2012-01-01

Reductions in mobility and cognitive function linked to accrual of brain microvascular disease related white-matter hyperintensities(WMH) on magnetic resonance imaging (MRI) canoccur in older hypertensive patients in as little as 2 years. We have designed a trial evaluating two levels of ambulatory BP control in individuals with normal or mildly impaired mobility and cognition who have detectable cerebrovascular disease (>0.5% WMH fraction of intracranial volume) on functional outcomes. The study is a prospective randomized, open-label trial with blinded endpoints, inpatients ages 75 and older with elevated 24-h systolic BP (≥145 mmHg in the untreated state) who do not have unstable cardiovascular disease, heart failure or stroke. The primary and key secondary outcomes in the trial are: change from baseline in mobility and cognitive function and damage to brain white matter as demonstrated by accrual of WMH volume and changes indiffusion tensor imaging.Approximately 300 patients will be enrolled and 200 randomized to one of two levels of ambulatory BP control (intensive to achieve a goal 24-hour systolic BP of ≤ 130 mmHg or standard to achieve a goal 24-hour systolic BP of ≤ 145 mmHg) for a total of 36 months using similar antihypertensive regimens. The analytical approach provides 85% power to show a clinically meaningful effect in differences in mobility accompanied by quantitative differences in WMH between treatment groups. The INFINITY trial is the first to guide antihypertensive therapy using ambulatory BP monitoring rather than clinic BP to reduce cerebrovascular disease. PMID:23453090

Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy

PubMed Central

Ghazi, Lama; Drawz, Paul

2017-01-01

The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the physiology of blood pressure control and the pathophysiology of hypertension (HTN) with effects on vascular tone, sodium retention, oxidative stress, fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents have been available to treat HTN since the 1970s and newer medications are being developed. In this review, we will (1) examine new anti-hypertensive medications affecting the RAAS, (2) evaluate recent studies that help provide a better understanding of which patients may be more likely to benefit from RAAS blockade, and (3) review three recent pivotal randomized trials that involve newer RAAS blocking agents and inform clinical practice. PMID:28413612

Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy.

PubMed

Ghazi, Lama; Drawz, Paul

2017-01-01

The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the physiology of blood pressure control and the pathophysiology of hypertension (HTN) with effects on vascular tone, sodium retention, oxidative stress, fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents have been available to treat HTN since the 1970s and newer medications are being developed. In this review, we will (1) examine new anti-hypertensive medications affecting the RAAS, (2) evaluate recent studies that help provide a better understanding of which patients may be more likely to benefit from RAAS blockade, and (3) review three recent pivotal randomized trials that involve newer RAAS blocking agents and inform clinical practice.

Hypertension Vaccine may be a boon to millions in developing world.

PubMed

Bairwa, Mohan; Pilania, Manju; Gupta, Vivek; Yadav, Kapil

2014-01-01

Hypertension affects around 40% adults aged 25 years and more worldwide, and accounts for 7% of total disability-adjusted life-years. A simple algorithmic program is required to manage hypertension consisting of screening, life style measures, treatment and follow-up, a reliable drug supply and distribution system, and a credible health information system. Despite availability of effective antihypertensive drugs, long term treatment is still costly, tedious, and at the population level rather unsuccessful. Hypertension leaves patients and families with an avoidable heavy economic burden due to failure to control blood pressure. Health policy needs to address gross imbalance between prevention and management by increasing contribution to the preventive programs. During 21st century, the risk factors for morbidity and mortality have been changed, and researchers have started to work upon vaccines against lifestyle diseases like hypertension, diabetes etc. Researchers began experimenting with vaccines against the renin-angiotensin system to control hypertension around six decades ago. The vaccine candidates against hypertension namely ATR12181, pHAV-4Ang IIs, CYT006-AngQb, AngI-R, ATRQβ-001 have shown promising results. A candidate vaccine, CYT006-AngQb, has crossed initial phase and moved into phase 2 trials. However, more human studies in subsequent phases of trials are required to establish the safety and efficacy of anti-hypertensive vaccine. If proved safe and cost effective, a vaccine even with 50% efficacy against hypertension may protect about 90 million people from hypertension and its heavy economic burden. It can be an appropriate solution for low compliance to antihypertensive drug therapy as well as an avalanche to induce efforts on various chronic disease vaccine development programs.

Epidural therapy for the treatment of severe pre-eclampsia in non labouring women.

PubMed

Ray, Amita; Ray, Sujoy

2017-11-28

Pre-eclampsia is a pregnancy-specific multi-organ disorder, which is characterised by hypertension and multisystem organ involvement and which has significant maternal and fetal morbidity and mortality. Failure of the placental vascular remodelling and reduced uteroplacental flow form the etiopathological basis of pre-eclampsia. There are several established therapies for pre-eclampsia including antihypertensives and anticonvulsants. Most of these therapies aim at controlling the blood pressure or preventing complications of elevated blood pressure, or both. Epidural therapy aims at blocking the vasomotor tone of the arteries, thereby increasing uteroplacental blood flow. This review was aimed at evaluating the available evidence about the possible benefits and risks of epidural therapy in the management of severe pre-eclampsia, to define the current evidence level of this therapy, and to determine what (if any) further evidence is required. To assess the effectiveness, safety and cost of the extended use of epidural therapy for treating severe pre-eclampsia in non-labouring women. This review aims to compare the use of extended epidural therapy with other methods, which include intravenous magnesium sulphate, anticonvulsants other than magnesium sulphate, with or without use of the antihypertensive drugs and adjuncts in the treatment of severe pre-eclampsia.This review only considered the use of epidural anaesthesia in the management of severe pre-eclampsia in the antepartum period and not as pain relief in labour. We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (13 July 2017) and reference lists of retrieved studies. Randomised controlled trials (RCTs) or quasi-RCTs comparing epidural therapy versus traditional therapy for pre-eclampsia in the form of antihypertensives, anticonvulsants, magnesium sulphate, low-dose dopamine, corticosteroids or a combination of these, were eligible for inclusion. Trials using a cluster design, and studies published in abstract form only are also eligible for inclusion in this review. Cross-over trials were not eligible for inclusion in this review. The two review authors independently assessed trials for inclusion and trial quality. There were no relevant data available for extraction. We included one small study (involving 24 women). The study was a single-centre randomised trial conducted in Mexico. This study compared a control group who received antihypertensive therapy, anticonvulsant therapy, plasma expanders, corticosteroids and dypyridamole with an intervention group that received epidural block instead of the antihypertensives, as well as all the other four drugs. Lumbar epidural block was given using 0.25% bupivacaine, 10 mg bolus and 5 mg each hour on continuous epidural infusion for six hours. This study was at low risk of bias in three domains but was assessed to be high risk of bias in two domains due to lack of allocation concealment and blinding of women and staff, and unclear for random sequence generation and outcome assessor blinding.The included study did not report on any of this review's important outcomes. Meta-analysis was not possible.For the mother, these were: maternal death (death during pregnancy or up to 42 days after the end of the pregnancy, or death more than 42 days after the end of the pregnancy); development of eclampsia or recurrence of seizures; stroke; any serious morbidity: defined as at least one of stroke, kidney failure, liver failure, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), disseminated intravascular coagulation, pulmonary oedema.For the baby, these were: death: stillbirths (death in utero at or after 20 weeks' gestation), perinatal deaths (stillbirths plus deaths in the first week of life), death before discharge from the hospital, neonatal deaths (death within the first 28 days after birth), deaths after the first 28 days; preterm birth (defined as the birth before 37 completed weeks' gestation); and side effects of the intervention. Reported outcomesThe included study only reported on a single secondary outcome of interest to this review: the Apgar score of the baby at birth and after five minutes and there was no clear difference between the intervention and control groups.The included study also reported a reduction in maternal diastolic arterial pressure. However, the change in maternal mean arterial pressure and systolic arterial pressure, which were the other reported outcomes of this trial, were not significantly different between the two groups. Currently, there is insufficient evidence from randomised controlled trials to evaluate the effectiveness, safety or cost of using epidural therapy for treating severe pre-eclampsia in non-labouring women.High-quality randomised controlled trials are needed to evaluate the use of epidural agents as therapy for treatment of severe pre-eclampsia. The rationale for the use of epidural is well-founded. However there is insufficient evidence from randomised controlled trials to show that the effect of epidural translates into improved maternal and fetal outcomes. Thus, there is a need for larger, well-designed studies to come to an evidence-based conclusion as to whether the lowering of vasomotor tone by epidural therapy results in better maternal and fetal outcomes and for how long that could be maintained. Another important question that needs to be answered is how long should extended epidural be used to ensure any potential clinical benefits and what could be the associated side effects and costs. Interactions with other modalities of treatment and women's satisfaction could represent other avenues of research.

Continuing or Temporarily Stopping Prestroke Antihypertensive Medication in Acute Stroke: An Individual Patient Data Meta-Analysis.

PubMed

Woodhouse, Lisa J; Manning, Lisa; Potter, John F; Berge, Eivind; Sprigg, Nikola; Wardlaw, Joanna; Lees, Kennedy R; Bath, Philip M; Robinson, Thompson G

2017-05-01

Over 50% of patients are already taking blood pressure-lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping preexisting antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ≤48 hours; investigating the effect of continuation versus stopping prestroke antihypertensive medication; and follow-up of ≥2 weeks. Two randomized controlled trials were identified and included in this meta-analysis of individual patient data from 2860 patients with ≤48 hours of acute stroke. Risk of bias in each study was low. In adjusted logistic regression and multiple regression analyses (using random effects), we found no significant association between continuation of prestroke antihypertensive therapy (versus stopping) and risk of death or dependency at final follow-up: odds ratio 0.96 (95% confidence interval, 0.80-1.14). No significant associations were found between continuation (versus stopping) of therapy and secondary outcomes at final follow-up. Analyses for death and dependency in prespecified subgroups revealed no significant associations with continuation versus temporarily stopping therapy, with the exception of patients randomized ≤12 hours, in whom a difference favoring stopping treatment met statistical significance. We found no significant benefit with continuation of antihypertensive treatment in the acute stroke period. Therefore, there is no urgency to administer preexisting antihypertensive therapy in the first few hours or days after stroke, unless indicated for other comorbid conditions. © 2017 American Heart Association, Inc.

[Antihypertensive treatment for patients with hypertension and diabetes type II--current clinical research].

PubMed

Rajzer, Marek; Kawecka-Jaszcz, Kalina; Wojciechowska, Wiktoria

2003-01-01

The frequency of arterial hypertension occurrence in polish population amounts to 30-40%, among diabetics is significantly higher-70%. According to the WHO/ISH Guidelines all hypertensive patients with diabetes are included into the "high risk group" independent of hypertension stage. Pharmacological treatment of hypertension is this group of patients has a particular meaning. Among hypertensive patients the degree of blood pressure lowering is more effective for cardiovascular risk reduction than choice of drug. This fact is well documented in clinical trials comparing antihypertensive efficacy of old and new antihypertensive drugs (for example UKPDS, STOP 2, INSIGHT). From the other point of view renal protection and metabolic benefits, as well as reduction of target organ damage are more advantageous for angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and calcium antagonists than for diuretics and beta-blockers. Despite fast progress in clinical research on new antihypertensive drugs (especially AT1 receptor inhibitors) ACE-I seem to still remain still the "first choice" for hypertensive diabetics. Adequate blood pressure control among diabetic hypertensives is of special importance and usually needs appropriate combined antihypertensive therapy. Our review presents detailed information about treatment advantages and disadvantages of drugs from different antihypertensive classes in light of current clinical trials and international guidelines.

Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis

PubMed Central

Espinosa, Angel; Ripollés–Melchor, Javier; Casans-Francés, Rubén; Abad-Gurumeta, Alfredo; Bergese, Sergio D.; Zuleta-Alarcon, Alix; López-Timoneda, Francisco; Calvo-Vecino, José María

2016-01-01

Background Clevidipine is an ultrashort-acting drug for rapid reduction of blood pressure by selectively acting on the L-type Ca2+ channels on arteriolar smooth muscle. The drug’s ultrashort action in reducing the blood pressure is due to its rapid hydrolysis by blood and extravascular tissue esterases, which does not depend on hepato-renal metabolism and excretion. An analysis of the perioperative management of blood pressure should be considered to compare with other intravenous antihypertensive agents. Methods Analyses of the available evidence in randomized clinical trials following the PRISMA methodology as well as clinical significance according to the GRADE system were conducted. Placebo versus other antihypertensive drugs studies were included. Statistical assessments were done using the X2 and I2 tests. Results Clevidipine was more effective in maintaining the blood pressure within pre-specified ranges compared with other antihypertensive drugs (MD, -17.87 CI 95%: -29.02 to -6.72; p = 0.02). The use of Clevidipine versus placebo and rescue antihypertensive intravenous drug showed a clear reduction in rates of treatment failure (RR 0.10; IC 95%; 0.05–0.18; p <0.0001). There was no difference in the incidence of adverse events compared with placebo (RR 1.47; 95% CI 0.89 to 2.43, p = 0.14) and with other antihypertensive drugs (RR 0.78, 95% CI 0.45 to 1.35; p = 0.37). In addition, there was no difference in the incidence of atrial fibrillation (AF) between clevidipine and control groups (RR 1.09, IC del 95%: 0.65 a 1.83; p = 0.73). Conclusions Clevidipine is an ultrafast-acting drug that is highly effective for management of perioperative arterial hypertension. It is devoid of adverse effects associated with the use of other IV antihypertensives. Its favorable pharmacodynamic and pharmacokinetic properties make clevidipine the drug of choice for the management of acute perioperative hypertension. It is important to emphasize the need for further studies with a larger number of patients to confirm these findings and increase the degree of evidence. PMID:27018586

Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis.

PubMed

Espinosa, Angel; Ripollés-Melchor, Javier; Casans-Francés, Rubén; Abad-Gurumeta, Alfredo; Bergese, Sergio D; Zuleta-Alarcon, Alix; López-Timoneda, Francisco; Calvo-Vecino, José María

2016-01-01

Clevidipine is an ultrashort-acting drug for rapid reduction of blood pressure by selectively acting on the L-type Ca2+ channels on arteriolar smooth muscle. The drug's ultrashort action in reducing the blood pressure is due to its rapid hydrolysis by blood and extravascular tissue esterases, which does not depend on hepato-renal metabolism and excretion. An analysis of the perioperative management of blood pressure should be considered to compare with other intravenous antihypertensive agents. Analyses of the available evidence in randomized clinical trials following the PRISMA methodology as well as clinical significance according to the GRADE system were conducted. Placebo versus other antihypertensive drugs studies were included. Statistical assessments were done using the X2 and I2 tests. Clevidipine was more effective in maintaining the blood pressure within pre-specified ranges compared with other antihypertensive drugs (MD, -17.87 CI 95%: -29.02 to -6.72; p = 0.02). The use of Clevidipine versus placebo and rescue antihypertensive intravenous drug showed a clear reduction in rates of treatment failure (RR 0.10; IC 95%; 0.05-0.18; p <0.0001). There was no difference in the incidence of adverse events compared with placebo (RR 1.47; 95% CI 0.89 to 2.43, p = 0.14) and with other antihypertensive drugs (RR 0.78, 95% CI 0.45 to 1.35; p = 0.37). In addition, there was no difference in the incidence of atrial fibrillation (AF) between clevidipine and control groups (RR 1.09, IC del 95%: 0.65 a 1.83; p = 0.73). Clevidipine is an ultrafast-acting drug that is highly effective for management of perioperative arterial hypertension. It is devoid of adverse effects associated with the use of other IV antihypertensives. Its favorable pharmacodynamic and pharmacokinetic properties make clevidipine the drug of choice for the management of acute perioperative hypertension. It is important to emphasize the need for further studies with a larger number of patients to confirm these findings and increase the degree of evidence.

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

PubMed Central

Curtis, J R; Bateman, F J

1975-01-01

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure. PMID:811312

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

PubMed

Curtis, J R; Bateman, F J

1975-11-22

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure.

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

PubMed

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

2013-05-01

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

[Classical antihypertensive drugs: diuretics].

PubMed

Nagy, Viktor László

2017-03-01

The diuretics are essential medicaments of antihypertensive therapy. They reduce blood pressure and cardiovascular events optimally. With increasing doses of thiazides and thiazide analogs do not come further powerful effect of reducing blood pressure or cardiovascular mortality and morbidity, but clearly elevate the side effects. Because of it, the minimum effective dose level and the fixed-dose combination therapy should be preferred. The use these drugs leads to especially positive outcome in elder patients, isolated systolic hypertension, heart failure, after stroke and in black population. Loop diuretics as antihypertensive therapy can be used only by renal impairment. The use of aldosterone antagonists can have a good effect not only on heart failure but also on prevention of atrial fibrillation. Furthermore, using it in a combination therapy with thiazides, it reduces the risk of hypokalemia. Therefore, the diuretic treatment in hypertension is flourishing again. Orv. Hetil., 2017, 158(11), 403-408.

Effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment: the DANTE Study Leiden.

PubMed

Moonen, Justine E F; Foster-Dingley, Jessica C; de Ruijter, Wouter; van der Grond, Jeroen; de Craen, Anton J M; van der Mast, Roos C

2016-03-01

the relationship between antihypertensive medication and orthostatic hypotension in older persons remains ambiguous, due to conflicting observational evidence and lack of data of clinical trials. to assess the effect of discontinuation of antihypertensive medication on orthostatic hypotension in older persons with mild cognitive impairment. a total of 162 participants with orthostatic hypotension were selected from the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study. This randomised clinical trial included community-dwelling participants aged ≥75 years, with mild cognitive impairment, using antihypertensive medication and without serious cardiovascular disease. Participants were randomised to discontinuation or continuation of antihypertensive treatment (ratio 1:1). Orthostatic hypotension was defined as a drop of at least 20 mmHg in systolic blood pressure and/or 10 mmHg in diastolic blood pressure on standing from a seated position. Outcome was the absence of orthostatic hypotension at 4-month follow-up. Relative risks (RR) were calculated by intention-to-treat and per-protocol analyses. at follow-up, according to intention-to-treat analyses, of the 86 persons assigned to discontinuation of antihypertensive medication, 43 (50%) were free from orthostatic hypotension, compared with 29 (38%) of the 76 persons assigned to continuation of medication [RR 1.31 (95% confidence interval (CI) 0.92-1.87); P = 0.13]. Per-protocol analysis showed that recovery from orthostatic hypotension was significantly higher in persons who completely discontinued all antihypertensive medication (61%) compared with the continuation group (38%) [RR 1.60 (95% CI 1.10-2.31); P = 0.01]. in older persons with mild cognitive impairment and orthostatic hypotension receiving antihypertensive medication, discontinuation of antihypertensive medication may increase the probability of recovery from orthostatic hypotension. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Design of the heart failure endpoint evaluation of AII-antagonist losartan (HEAAL) study in patients intolerant to ACE-inhibitor.

PubMed

Konstam, Marvin A; Poole-Wilson, Philip A; Dickstein, Kenneth; Drexler, Helmut; Justice, Steven J; Komajda, Michel; Malbecq, William; Martinez, Felipe A; Neaton, James D; Riegger, Gunter A J; Guptha, Soneil

2008-09-01

In patients with heart failure and reduced left ventricular ejection fraction, angiotensin receptor blockers have been found to reduce mortality and morbidity and to prevent or reverse left ventricular remodelling, compared to optimized background treatment. In light of these data, The Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan (HEAAL) study was developed to determine whether losartan 150 mg is superior to losartan 50 mg (antihypertensive dose) in reducing morbidity and mortality among patients with symptomatic heart failure who are intolerant of angiotensin-converting enzyme (ACE)-inhibitors. To compare the effect of high and moderate doses of losartan on the primary endpoint of all-cause mortality and hospitalisation due to heart failure in patients (n = 3834) with symptomatic heart failure and an ejection fraction < or = 40% who are intolerant of ACE-inhibitor treatment. This paper presents the rationale, trial design, and baseline characteristics of the study population. The study, which completed recruitment on 31 March 2005, is event-driven and is estimated to accrue the target of 1710 adjudicated primary events during the latter half of 2008. The results of HEAAL should facilitate selection of an optimal dosing regimen for losartan in patients with symptomatic heart failure who are intolerant of ACE-inhibitors.

The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications.

PubMed

Kandzari, David E; Kario, Kazuomi; Mahfoud, Felix; Cohen, Sidney A; Pilcher, Garrett; Pocock, Stuart; Townsend, Raymond; Weber, Michael A; Böhm, Michael

2016-01-01

Renal sympathetic activation plays a key role in the pathogenesis of hypertension, as demonstrated by high renal norepinephrine spillover into plasma of patients with essential hypertension. Renal denervation has demonstrated a significant reduction in blood pressure in unblinded studies of hypertensive patients. The SYMPLICITY HTN-3 trial, the first prospective, masked, randomized study of renal denervation versus sham control, failed its primary efficacy end point and raised important questions around potentially confounding factors, such as drug changes and adherence, study population, and procedural methods. The SPYRAL HTN Global Clinical Trial Program is designed to address limitations associated with predicate studies and provide insight into the impact of pharmacotherapy on renal denervation efficacy. The 2 initial trials of the program focus on the effect of renal denervation using the Symplicity Spyral multielectrode renal denervation catheter in hypertensive patients in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. The SPYRAL HTN ON-MED study requires patients to be treated with a consistent triple therapy antihypertensive regimen, whereas the SPYRAL HTN OFF-MED study includes a 3- to 4-week drug washout period followed by a 3-month efficacy and safety end point in the absence of antihypertensive medications. The studies will randomize patients with combined systolic-diastolic hypertension to renal denervation or sham procedure. Both studies allow renal denervation treatments in renal artery branches and accessories. These studies will inform the design of the second pivotal phase of the program, which will more definitively analyze the antihypertensive effect of renal denervation. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of calcium channel blockers comparing to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with hypertension and chronic kidney disease stage 3 to 5 and dialysis: A systematic review and meta-analysis

PubMed Central

Lin, Yen-Chung; Lin, Jheng-Wei; Wu, Mai-Szu; Chen, Kuan-Chou; Peng, Chiung-Chi

2017-01-01

Background Calcium channel blocker (CCB) or two renin angiotensin aldosterone system blockades (RAAS), angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are major potent and prevalently used as initial antihypertensive agents for mild to moderate hypertension, but no uniform agreement as to which antihypertensive drugs should be given for initial therapy, especially among chronic kidney disease (CKD) patients. Design A systematic review and meta-analysis comparing CCBs and the two RAAS blockades for hypertensive patients with CKD stage 3 to 5D. The inclusion criteria for this systematic review was RCT that compared the effects of CCBs and the two RAAS blockades in patients with hypertension and CKD. The exclusion criteria were (1) renal transplantation, (2) CKD stage 1 or 2, (3) combined therapy (data cannot be extracted separately). Outcomes were blood pressure change, mortality, heart failure, stroke or cerebrovascular events, and renal outcomes. Results 21 randomized controlled trials randomized 9,492 patients with hypertensive and CKD into CCBs and the two RAAS blockades treatments. The evidence showed no significant differences in blood presser change, mortality, heart failure, stroke or cerebrovascular events, and renal outcomes between CCBs group and the two RAAS blockades group. The publication bias of pooled mean blood presser change that was detected by Egger’s test was non-significant. Conclusions CCBs has similar effects on long term blood pressure, mortality, heart failure, stroke or cerebrovascular events, and renal function to RAAS blockades in patients CKD stage 3 to 5D and hypertension. PMID:29240784

The economic returns of pediatric clinical trials of anti-hypertensive drugs

PubMed Central

Baker-Smith, Carissa M.; Benjamin, Daniel K.; Grabowski, Henry G.; Reid, Elizabeth D.; Mangum, Barry; Goldsmith, John V.; Murphy, M. Dianne; Edwards, Rex; Eisenstein, Eric L.; Sun, Jessica; Califf, Robert M.; Li, Jennifer S.

2012-01-01

Background Congress has authorized the U.S. Food and Drug Administration (FDA) to provide industry sponsors with a 6-month extension of drug marketing rights under the Pediatric Exclusivity Provision if FDA-requested pediatric drug trials are conducted. The cost and economic return of pediatric exclusivity to industry sponsors has been shown to be highly variable. We sought to determine the cost of performing pediatric exclusivity trials within a single therapeutic area and the subsequent economic return to industry sponsors. Methods We evaluated 9 orally administered anti-hypertensive drugs submitted to the FDA under the Pediatric Exclusivity Provision from 1997–2004 and obtained key elements of the clinical trial designs and operations. Estimates of the costs of performing the studies were generated and converted into after-tax cash outflow. Market sales were obtained and converted into after-tax inflows based on 6 months of additional patent protection. Net economic return and net return-to-cost ratios were determined for each drug. Results Of the 9 anti-hypertensive agents studied, an average of 2 studies per drug was performed, including at least 1 pharmacokinetic study and a safety and efficacy study. The median cost of completing a pharmacokinetic trial was $862,000 (range: $556,000–1.8 million). The median cost of performing safety and efficacy trials for these agents was $4.3 million (range: $2.1 million–12.9 million). The ratio of net economic return to cost was 17 (range: 4–64.7). Conclusion We found that, within a cohort of anti-hypertensive drugs, the Pediatric Exclusivity Provision has generated highly variable, yet lucrative returns to industry sponsors. PMID:18926149

Heart failure and the discrepancy between trials of intensive blood pressure management: an analysis of individual patient data.

PubMed

Aggarwal, Rahul; Mirzan, Haares; Chiu, Nicholas; Steinkamp, Jackson

2018-02-26

ACCORD and SPRINT are the best randomized controlled trial data evaluating the effects of blood pressure targets below 140 mmHg. These trials had contradictory results regarding the benefits of intensive antihypertensive therapy. We investigate if this discordance was driven by SPRINT's inclusion of Heart Failure in its primary outcome, as this is a parameter not included in ACCORD's original primary outcome. This analysis helps to resolve a significant area of contention. Individual patient data from 4733 participants in ACCORD were analyzed from time of randomization. All participants were diabetic and at increased cardiovascular risk. Participants were assigned to their original intervention, a standard blood pressure target of less than 140 mmHg or an intensive target of less than 120 mmHg. Primary composite outcome was defined as in SPRINT: a composite of first occurrence of myocardial infarction, stroke, heart failure, death from cardiovascular causes, and other acute coronary syndromes. Primary outcome was not significantly different between standard and intensive groups [HR: 0.89; 95% CI: (0.76-1.03); p = 0.108]. The primary composite outcome occurred in 370 participants in the standard group (15.6%) and 324 participants in the intensive group (13.7%), with an event rate of 3.38% per year for the standard group and 3.01% per year for the intensive group. Differing results between ACCORD and SPRINT are not attributable to ACCORD's exclusion of Heart Failure from its original primary outcome measurement. No significant differences in primary outcome were observed between intensive and standard blood pressure groups in the ACCORD patients under the SPRINT primary outcome definition. Caution should be taken in extrapolating the intensive blood pressure control benefits of SPRINT to the diabetic population.

Current role of beta-blockers in the treatment of hypertension.

PubMed

Aronow, Wilbert S

2010-11-01

It is important to know which patients with hypertension will benefit from beta-blocker therapy and which beta-blockers should be used in the treatment of hypertension to reduce cardiovascular events and mortality. Studies between 1981 and 2009 using a Medline search are reported. Beta-blockers should be used to treat hypertension in patients with previous myocardial infarction, acute coronary syndromes, angina pectoris, congestive heart failure, ventricular arrhythmias, supraventricular tachyarrhythmias, diabetes mellitus, after coronary artery bypass graft surgery, and in patients who are pregnant, have thyrotoxicosis, glaucoma, migraine, essential tremor, perioperative hypertension, or an excessive blood pressure response after exercise. The use of beta-blockers as first-line therapy in patients with primary hypertension has been controversial. However, the 2009 guidelines of the European Society of Hypertension state that large-scale meta-analyses of available data confirm that diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers do not significantly differ in their ability to lower blood pressure and to exert cardiovascular protection both in elderly and in younger patients. The key message of this paper is that atenolol should not be used as an antihypertensive drug and that the degree of reduction of mortality, myocardial infarction, stroke and congestive heart failure by antihypertensive therapy is dependent on the degree of lowering of aortic blood pressure. Newer vasodilator beta-blockers such as carvedilol and nebivolol may be more effective in reducing cardiovascular events than traditional beta-blockers, but this needs to be investigated by controlled clinical trials.

Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016

PubMed Central

Fahl Mar, Kaysee; Schilling, Joshua; Brown, Walter A.

2018-01-01

Background Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension. Method For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms). Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures. Results Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018) and effect size (R2 = 0.013, p = 0.187) drug-placebo difference (R2 = 0.013, p = 0.182) and success rate (134/142, 94.4%) have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, p<0.001). Treatment arms are likely overpowered with sample sizes increasing over time (R2 = 0.387, p<0.0001) and stable, large effect sizes (0.78 ±0.37). The exploratory analysis of sample size, trial duration, baseline blood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877), antihypertensive-placebo differences (p = 0.752), or p-values (p = 0.963) but was correlated with antihypertensive response (R2 = 0.347, p<0.0001). Conclusions As hypothesized, this study shows that placebo response is increasing in clinical trials for hypertension without any evidence of this increase impacting trial outcomes. Attempting to control placebo response in clinical trials for hypertension may not be necessary for successful efficacy outcomes. In exploratory analysis, we noted that despite finding significant relationships, none of the trial or patient characteristics we examined offered a clear explanation of the rise in placebo and stability in outcome measures over time. Collectively, these data suggest that the phenomenon of increasing placebo response and stable efficacy outcomes may be a general trend, occurring across trials for various psychiatric and medical conditions with physiological and non-physiological endpoints. PMID:29489874

Candesartan cilexetil: an angiotensin II receptor blocker.

PubMed

Stoukides, C A; McVoy, H J; Kaul, A F

1999-12-01

To summarize and critique the medical literature on candesartan cilexetil, an angiotensin II receptor blocker (ARB). MEDLINE searches (January 1966-January 1999) and manufacturer prescribing literature were used to identify articles on candesartan cilexetil. Bibliographies were also reviewed for germane articles. Study and review articles describing the chemistry, human pharmacology, pharmacodynamics, pharmacokinetics, placebo-controlled trials, comparative trials, and clinical application of candesartan cilexetil based on the published literature and premarketing clinical trials were reviewed. All literature on the use of candesartan cilexetil for treating hypertension and congestive heart failure were included. ARBs are a new class of drugs with increasing use in treating hypertension. Studies are ongoing to determine the role of these agents in preventing remodeling after myocardial infarction and in patients with congestive heart failure. Candesartan cilexetil is among the newest drugs in the class that includes losartan, irbesartan, and valsartan. Candesartan cilexetil has more than 1000 times more affinity for the angiotensin II, type AT1 receptor ARBs, and the binding affinity and competitive angiotensin II receptor antagonism is stronger than that of losartan. Clinical studies in patients with hypertension have demonstrated that candesartan cilexetil, in doses of 4-16 mg, is more effective in reducing sitting diastolic blood pressure than are placebo and losartan 50 mg. Candesartan cilexetil has demonstrated reductions in blood pressure comparable to those of enalapril, with the rate of adverse events greater in the enalapril group. Dosage adjustments are not necessary in elderly patients or in patients with mild hepatic or renal dysfunction. In diabetic patients, blood glucose, hemoglobinA1c, and serum lipids are not affected. The clinical studies demonstrated that the adverse effect profile of candesartan cilexetil was similar to that of placebo and there were no dose-dependent adverse effects. Candesartan cilexetil provides an alternative antihypertensive therapy that is well tolerated and effective in reducing blood pressure in a wide range of patients. Due to its greater binding affinity to the angiotensin II receptor, candesartan cilexetil appears to have a longer antihypertensive effect than losartan. This may be advantageous in decreasing morbidity and mortality associated with hypertension, although further studies are required to validate this potential advantage.

Refractory Hypertension: Determination of Prevalence, Risk Factors and Comorbidities in a Large, Population-Based Cohort

PubMed Central

Calhoun, David A.; Booth, John N.; Oparil, Suzanne; Irvin, Marguerite R.; Shimbo, Daichi; Lackland, Daniel T.; Howard, George; Safford, Monika M.; Muntner, Paul

2014-01-01

Refractory hypertension is an extreme phenotype of antihypertensive treatment failure. Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a large (n=30,239), population-based cohort were evaluated to determine the prevalence of refractory hypertension and associated cardiovascular risk factors and comorbidities. Refractory hypertension was defined as uncontrolled blood pressure (systolic/diastolic ≥ 140/90 mm Hg) on ≥ 5 antihypertensive drug classes. Participants with resistant hypertension (systolic/diastolic ≥140/90 mm Hg on ≥ 3 or<140/90 mm Hg on ≥ 4 antihypertensive classes) and all treated hypertensive participants served as comparator groups. Of 14,809 REGARDS participants receiving antihypertensive treatment, 78 (0.5%) had refractory hypertension. The prevalence of refractory hypertension was 3.6% among participants with resistant hypertension(n=2,144) and 41.7% among participants on 5 or more antihypertensive drug classes. Among all hypertensive participants, African American race, male gender, living in the stroke belt or buckle, higher body mass index, lower heart rate, reduced estimated glomerular filtration rate, albuminuria, diabetes and history of stroke and coronary heart disease were associated with refractory hypertension. Compared to resistant hypertension, prevalence ratios for refractory hypertension were increased for African Americans (3.00, 95% CI 1.68 – 5.37) and those with albuminuria (2.22, 95% CI 1.40 – 3.52) and diabetes (2.09, 95% CI 1.32 – 3.31). The median 10-year Framingham risk for coronary heart disease and stroke was higher among participants with refractory hypertension compared to either comparator group. These data indicate that while resistant hypertension is relatively common among treated hypertensive patients, true antihypertensive treatment failure is rare. PMID:24324035

Run-up to participation in ATACH II in Japan

PubMed Central

Toyoda, K; Sato, S; Koga, M; Yamamoto, H; Nakagawara, J; Furui, E; Shiokawa, Y; Hasegawa, Y; Okuda, S; Sakai, N; Kimura, K; Okada, Y; Yoshimura, S; Hoshino, H; Uesaka, Y; Nakashima, T; Itoh, Y; Ueda, T; Nishi, T; Gotoh, J; Nagatsuka, K; Arihiro, S; Yamaguchi, T; Minematsu, K

2012-01-01

Intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality in Japan. Seventeen Japanese institutions are participating in the Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH) II Trial (ClinicalTrials.gov no. NCT01176565; UMIN 000006526). This phase III trial is designed to determine the therapeutic benefit of early intensive systolic blood pressure (BP) lowering for acute hypertension in ICH patients. This report explains the long run-up to reach the start of patient registration in ATACH II in Japan, including our preliminary study, a nationwide survey on antihypertensive treatment for acute ICH patients, a multicenter study for hyperacute BP lowering (the SAMURAI-ICH study), revision of the official Japanese label for intravenous nicardipine, and construction of the infrastructure for the trial. PMID:23230457

Antihypertensive use and the effect of a physical activity intervention in the prevention of major mobility disability among older adults: The LIFE study

USDA-ARS?s Scientific Manuscript database

BACKGROUND: This subgroup analysis of the Lifestyle Intervention and Independence for Elders trial evaluates the impact of a long-term physical activity (PA) intervention on rates of major mobility disability (MMD) among older adults according to their antihypertensive medication use. METHODS: Lifes...

Current Status of Renal Denervation in Hypertension.

PubMed

Briasoulis, Alexander; Bakris, George L

2016-11-01

Over the past 7 years, prospective cohorts and small randomized controlled studies showed that renal denervation therapy (RDN) in patients with resistant hypertension is safe but associated with variable effects on BP which are not substantially better than medical therapy alone. The failure of the most rigorously designed randomized sham-control study, SYMPLICITY HTN-3, to meet the efficacy endpoints has raised several methodological concerns. However, recently reported studies and ongoing trials with improved procedural characteristics, identification of patients with true treatment-resistant hypertension on appropriate antihypertensive regimens further explore potential benefits of RDN. The scope of this review is to summarize evidence from currently completed studies on RDN and discuss future perspectives of RDN therapy in patients with resistant hypertension.

Systematic review: antihypertensive drug therapy in patients of African and South Asian ethnicity.

PubMed

Brewster, Lizzy M; van Montfrans, Gert A; Oehlers, Glenn P; Seedat, Yackoob K

2016-04-01

Despite the large differences in the epidemiology of hypertension across Europe, treatment strategies are similar for national populations of white European descent. However, hypertensive patients of African or South Asian ethnicity may require ethnic-specific approaches, as these population subgroups tend to have higher blood pressure at an earlier age that is more difficult to control, a higher occurrence of diabetes, and more target organ damage with earlier cardiovascular mortality. Therefore, we systematically reviewed the evidence on antihypertensive drug treatment in South Asian and African ethnicity patients. We used the Cochrane systematic review methodology to retrieve trials in electronic databases including CENTRAL, PubMed, and Embase from their inception through November 2015; and with handsearch. We retrieved 4596 reports that yielded 35 trials with 7 classes of antihypertensive drugs in 25,540 African ethnicity patients. Aside from the well-known blood pressure efficacy of calcium channel blockers and diuretics, with lesser effect of ACE inhibitors and beta-blockers, nebivolol was not more effective than placebo in reducing systolic blood pressure levels. Trials with morbidity and mortality outcomes indicated that lisinopril and losartan-based therapy were associated with a greater incidence of stroke and sudden death. Furthermore, 1581 reports yielded 16 randomized controlled trials with blood pressure outcomes in 1719 South Asian hypertensive patients. In contrast with the studies in African ethnicity patients, there were no significant differences in blood pressure lowering efficacy between drugs, and no trials available with mortality outcomes. In conclusion, in patients of African ethnicity, treatment initiated with ACE inhibitor or angiotensin II receptor blocker monotherapy was associated with adverse cardiovascular outcomes. We found no evidence of different efficacy of antihypertensive drugs in South Asians, but there is a need for trials with morbidity and mortality outcomes. Screening for cardiovascular risk at a younger age, treating hypertension at lower thresholds, and new delivery models to find, treat and follow hypertensives in the community may help reduce the excess cardiovascular mortality in these high-risk groups.

[Achievements and problems of modern trials of antihypertensive drugs].

PubMed

Kobalava, Zh D; Kotovskaia, Iu V

2011-01-01

Most important value of lowering of substantially elevated arterial pressure (AP) for improvement of outcomes in patients with arterial hypertension (AH) was convincingly confirmed by large truly placebo controlled randomized clinical trials (RCT) with the use of mainly diuretics, and/or beta-adrenoblockers in the 60-80ths. Later comparative RCT confirmed equal antihypertensive efficacy of 5 main drug classes relative to AP level in brachial artery. In this review we discuss merit of auxiliary class-specific properties of antihypertensive agents potentially affecting prognosis besides AP lowering. We also discuss problems related to decline of significance of quantitative criteria of AH and consideration of AP level in general context of cardiovascular risk; problems of external validity of RCT; extrapolation of RCT results obtained in patients with complicated AH and very high cardiovascular risk on young patients with uncomplicated AH; significance of hard and surrogate end points.

[120 mmHg for everyone?].

PubMed

Wiersma, Tjerk

2016-01-01

The recently published Systolic Blood Pressure Intervention Trial (SPRINT) casts new light on the issue of lowering blood pressure to 120 mmHg. The trial randomized 9161 patients with systolic blood pressures of 130 mmHg - 180 mmHg and increased cardiovascular risk into a group receiving intensive treatment (target 120 mmHg) and a group given standard treatment (target 140 mmHg). The trial was stopped earlier than foreseen because interim analysis showed a lower incidence rate of myocardial infarction, stroke, heart failure and death from cardiovascular causes in the group given intensive treatment (1.65 versus 2.19 per year, hazard ratio 0.75; 95% CI 0.64-0.89; p < 0.001). These results open up the possibility of aiming for lower blood pressure targets in antihypertensive treatment. It is questionable whether this strategy would be preferred by every patient. New guidelines on cardiovascular risk management should pay more attention to shared decision-making where doctors inform patients about the benefits and risks of strict or less strict blood pressure control and patients choose personal targets.

Treatment efficacy of anti-hypertensive drugs in monotherapy or combination

PubMed Central

Paz, Marco A.; de-La-Sierra, Alejandro; Sáez, Marc; Barceló, María Antonia; Rodríguez, Juan José; Castro, Sonia; Lagarón, Cristina; Garrido, Josep M; Vera, Pilar; Coll-de-Tuero, Gabriel

2016-01-01

Abstract Background: The relative efficacy of antihypertensive drugs/combinations is not well known. Identifying the most effective ones and the patients’ characteristics associated with best performance of the drugs will improve management of hypertensive patients. Objective: To assess the blood pressure (BP) reduction attributed to antihypertensive drugs and identify characteristics associated with BP decrease. Data sources: MEDLINE, Cochrane Central Register of Controlled Trials from inception through July 2012 and selected papers. Study eligibility criteria: Double-blind, randomized clinical trials whose main result was the reduction in BP by antihypertensive treatment, with study population ≥50 or ≥25 if the study was a crossover, follow-up of at least 8 weeks, and available required data. Study appraisal and synthesis methods: Study data were independently extracted by multiple observers and introduced in an electronic database. Inconsistencies were resolved by discussion and referral back to the original articles. Meta-analysis was performed according to PRISMA statement and using a Bayesian framework. Main Outcome(s) and Measure(s): Mean decrease in systolic (SBP) and diastolic blood pressure (DBP) achieved by each drug or combination. Results: Two hundred eight trials including 94,305 patients were identified. In monotherapy, most drugs achieved 10 to 15 mm Hg SBP and 8 to 10 mm Hg DBP decreases. Olmesartan/amlodipine, olmesartan/hydrochlorothiazide, felodipine/metoprolol, and valsartan/hydrochlorothiazide were the combinations leading to the greatest mean SBP reductions (>20 mm Hg). Female sex and body mass index >25 kg/m2 were associated with more pronounced SBP and DBP reductions, whereas Afro-American ethnicity was associated with BP reductions smaller than the median. Results were adjusted by study duration, cardiovascular disease, and diabetes mellitus. Still, the estimation was performed using the mean administered doses, which do not exactly match those of the available drug formats. Limitations: Data corresponded to those obtained in each of the included trials; the analysis of the combinations was limited to the most recent ones; estimations were performed using the mean administered doses. Conclusions and implications: Certain drug combinations achieve BP reductions ranging from 20 to 25/10 to 15 mm Hg. Sex, ethnicity, and obesity are associated with antihypertensive response. This information can contribute to better selection of the antihypertensive drug, depending on the magnitude of pretreatment BP elevation. Guidelines should be revised. PMID:27472680

Heterogeneity of Clinical Trials for Antihypertensive Drugs in Japan: Exploratory Analysis of Confirmatory Phase III Trials Used for Marketing Approval.

PubMed

Kaneko, Reina; Sano, Kota; Ono, Shunsuke

2018-07-01

The results of pivotal trials, which provide a rationale for marketing approval decisions for new drugs, are considered for various comparative purposes in postmarketing analyses. Using meta-regression analysis of 91 randomized controlled trials of 61 approved antihypertensive drugs in Japan, we show that mean baseline blood pressure (BP) of each arm was associated with predetermined entry criteria (EC), age, and trial start year (TSY). BP changes following treatment were associated with EC, subject characteristics (e.g., age, complications, baseline BP), study design (e.g., concomitant drug use), and TSY. Effect sizes were generally larger in trials for the first and second drugs in the same class than in trials for follow-on drugs. Results of pivotal trials may vary depending on many factors, suggesting possible challenges associated with the comparison of these results indirectly. Due to the heterogeneity in pivotal trials, caution should be exercised when comparing approved drugs and conducting meta-analyses retrospectively. © 2017, The American Society for Clinical Pharmacology and Therapeutics.

Clinical Trials of Blood Pressure Lowering and Antihypertensive Medication: Is Cognitive Measurement State-of-the-Art?

PubMed

Elias, Merrill F; Torres, Rachael V; Davey, Adam

2018-05-07

Randomized controlled trials of blood pressure (BP) lowering and antihypertensive medication use on cognitive outcomes have often been disappointing, reporting mixed findings and small effect sizes. We evaluate the extent to which cognitive assessment protocols used in these trials approach state-of-the-art. Overall, we find that a primary focus on cognition and the systematic selection of cognitive outcomes across trials take a backseat to other trial goals. Twelve trials investigating change in cognitive functioning were examined and none met criteria for state-of-the-art assessment, including use of at least 4 tests indexing 2 cognitive domains. Four trials investigating incident dementia were also examined. Each trial used state-of-the-art diagnostic criteria to assess dementia, although follow-up periods were relatively short, with only 2 trials lasting for at least 3 years. Weaknesses in each trial may act to obscure or weaken the positive effects of BP lowering on cognitive functioning. Improving trial designs in terms of cognitive outcomes selected and length of follow-up periods employed could lead to more promising findings. We offer logical steps to achieve state-of-the-art assessment protocols, with examples, in hopes of improving future trials.

Blood Pressure Control and Cardiovascular Outcomes in Normal, Overweight, and Obese Hypertensives Treated with Three Different Anti-Hypertensives in ALLHAT

PubMed Central

Reisin, Efrain; Graves, John; Yamal, Jose-Miguel; Barzilay, Joshua I; Pressel, Sara; Einhorn, Paula T.; Dart, Richard A.; Retta, Tamrat M.; Saklayen, Mohammad G.; Davis, Barry R

2017-01-01

Objective Epidemiologically there is a strong relationship between body mass index (BMI) and blood pressure (BP) levels. We prospectively examined randomization to first-step chlorthalidone, a thiazide-type diuretic; amlodipine, a calcium-channel blocker; and lisinopril, an angiotensin-converting-enzyme inhibitor, on BP control and cardiovascular outcomes in a hypertensive cohort stratified by baseline BMI (normal weight [BMI<25], overweight [BMI=25–29·9], and obese [BMI≥30]). Methods 33,357 hypertensive participants, age ≥55 years were followed for an average of 4·9 years in a randomized, double-blind, practice-based Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), for primary outcome of fatal coronary heart disease (CHD) or nonfatal myocardial infarction and secondary outcomes of stroke, heart failure, combined cardiovascular disease, mortality, and renal failure. Results Of participants, 37·9% were overweight and 42·1% were obese at randomization. For each medication, BP control (<140/90 mmHg) was equivalent in each BMI stratum. At year five, 66·1%, 66·5%, and 65·1% of normal weight, overweight, and obese participants, respectively, were controlled. Those randomized to chlorthalidone had highest BP control (67·2%, 68·3%, and 68·4%, respectively) and lisinopril the lowest (60·4%, 63·2%, and 59·6%, respectively) in each BMI stratum. A significant interaction (p=0·004) suggests a lower CHD risk in the obese for lisinopril vs. chlorthalidone (hazard ratio [HR]=0·85, 95% confidence interval [CI]=[0·74–0·98]) and a significant interaction (p=0·011) suggests a higher risk of end-stage renal disease for amlodipine vs. chlorthalidone in obese participants (HR [95% CI]=1·49[1·06–2·08]). However, these results were not consistent among other outcomes. Conclusions BMI status does not modify the effects of antihypertensive medications on BP control or cardiovascular disease outcomes. PMID:24842697

Improvement in hypertension in patients with diabetes mellitus after kidney/pancreas transplantation.

PubMed

Elliott, M D; Kapoor, A; Parker, M A; Kaufman, D B; Bonow, R O; Gheorghiade, M

2001-07-31

Hypertension persists in many patients with diabetes mellitus after kidney transplantation. However, the impact of control of diabetes as well as kidney failure on hypertension by combined kidney and pancreas transplantation has not been studied. Between March 1993 and August 1998, 111 patients with type 1 diabetes mellitus underwent successful pancreas transplantation (108 kidney/pancreas transplantation) and another 28 patients with type 1 diabetes mellitus underwent isolated kidney transplantation. Blood pressure measurements and all antihypertensive medications were determined for both groups before transplantation and at 1, 3, 6, and 12 months and at the most recent outpatient evaluation after transplantation. At baseline, the mean blood pressure was 151/88 and 151/83 mm Hg for the kidney/pancreas and isolated kidney transplant patients, respectively. The mean blood pressure decreased to 134/77 mm Hg 1 month after kidney/pancreas transplantation (P<0.001) and decreased further to 126/70 mm Hg (P<0.001) at a mean follow-up of 18 months. This reduction in blood pressure after transplantation occurred despite a decrease in antihypertensive medications and the institution of immunosuppressive agents. At 1 month after kidney/pancreas transplantation, the average number of antihypertensive medications per patient was 0.9+/-1.0, compared with 2.5+/-1.1 before surgery (P<0.001). At 18 months after transplantation, 34% of patients were both normotensive (blood pressure

Balancing commercial and public interests

PubMed Central

Furberg, Curt D; Hall, Mark A; Sevick, Mary Ann

2004-01-01

A large number of randomized clinical trials with important health outcomes are completed each year. Those with favorable findings are typically reported and published rapidly, while the publication of those with unfavorable results is often delayed or given a positive "spin." This observation applies primarily to industry-sponsored trials. Our objectives are to discuss the responsibility of pharmaceutical firms to the public with respect to timely, complete, and unbiased information from all randomized clinical trials and to propose solutions for improvements. We believe that in addition to financial obligations to their shareholders, pharmaceutical companies have social responsibilities to the public and to health care providers. However, private markets do not reward or compel optimal disclosure of drug safety or inferiority information on a voluntary basis. A problem which has not previously been identified relates to non-comparability of drugs. A case report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) illustrates how public interests may be violated due to failure to inform about drug inferiority. The current system for dissemination of relevant medical information could be improved if all involved parties collaborated fully. However, full disclosure of trial results is unlikely when research results are unfavorable to the firm. We conclude that expanded government regulations will be required for a satisfactory solution to the problem. PMID:15239846

Long-term follow-up of moderately hypercholesterolemic hypertensive patients following randomization to pravastatin vs. usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)

PubMed Central

Margolis, Karen L.; Davis, Barry R.; Baimbridge, Charles; Ciocon, Jerry O.; Cuyjet, Aloysius B.; Dart, Richard A.; Einhorn, Paula T.; Ford, Charles E.; Gordon, David; Hartney, Thomas J; Haywood, L. Julian; Holtzman, Jordan; Mathis, David E.; Oparil, Suzanne; Probstfield, Jeffrey L.; Simpson, Lara M.; Stokes, John D.; Wiegmann, Thomas B.; Williamson, Jeff D.

2015-01-01

A randomized, controlled, multicenter trial assigned well-controlled hypertensive participants ≥55 years, with moderate hypercholesterolemia to receive pravastatin (n=5170) or usual care (n=5185) for 4-8 years, when trial therapy was discontinued. Passive surveillance using national databases to ascertain deaths and hospitalizations continued for total follow-up of 8-13 years to assess whether mortality and morbidity differences persisted or new differences developed. During the post-trial period, fatal and nonfatal outcomes were available for 98% and 64% of participants, respectively. Primary outcome was all-cause mortality; secondary outcomes included cardiovascular mortality, coronary heart disease (CHD), stroke, heart failure, cardiovascular disease, and end-stage renal disease. No significant differences appeared in mortality for pravastatin versus usual care (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03), or other secondary outcomes. Similar to the previously reported in-trial result, there was a significant treatment effect for CHD in Blacks (HR, 0.79; 95% CI, 0.64-0.98). However, the in-trial result showing a significant treatment by race effect did not remain significant over the entire follow-up (P=.08). These findings are consistent with evidence from other large trials that show statins prevent CHD and add evidence that they are effective for CHD prevention in Blacks. PMID:23889716

Using Bayesian Adaptive Trial Designs for Comparative Effectiveness Research: A Virtual Trial Execution.

PubMed

Luce, Bryan R; Connor, Jason T; Broglio, Kristine R; Mullins, C Daniel; Ishak, K Jack; Saunders, Elijah; Davis, Barry R

2016-09-20

Bayesian and adaptive clinical trial designs offer the potential for more efficient processes that result in lower sample sizes and shorter trial durations than traditional designs. To explore the use and potential benefits of Bayesian adaptive clinical trial designs in comparative effectiveness research. Virtual execution of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) as if it had been done according to a Bayesian adaptive trial design. Comparative effectiveness trial of antihypertensive medications. Patient data sampled from the more than 42 000 patients enrolled in ALLHAT with publicly available data. Number of patients randomly assigned between groups, trial duration, observed numbers of events, and overall trial results and conclusions. The Bayesian adaptive approach and original design yielded similar overall trial conclusions. The Bayesian adaptive trial randomly assigned more patients to the better-performing group and would probably have ended slightly earlier. This virtual trial execution required limited resampling of ALLHAT patients for inclusion in RE-ADAPT (REsearch in ADAptive methods for Pragmatic Trials). Involvement of a data monitoring committee and other trial logistics were not considered. In a comparative effectiveness research trial, Bayesian adaptive trial designs are a feasible approach and potentially generate earlier results and allocate more patients to better-performing groups. National Heart, Lung, and Blood Institute.

Early antihypertensive treatment and clinical outcomes in acute ischemic stroke: subgroup analysis by baseline blood pressure.

PubMed

He, William J; Zhong, Chongke; Xu, Tan; Wang, Dali; Sun, Yingxian; Bu, Xiaoqing; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Zhang, Jintao; Geng, Deqin; Zhang, Jianhui; Li, Dong; Li, Yongqiu; Yuan, Xiaodong; Zhang, Yonghong; Kelly, Tanika N

2018-06-01

We studied the effect of early antihypertensive treatment on death, major disability, and vascular events among patients with acute ischemic stroke according to their baseline SBP. We randomly assigned 4071 acute ischemic stroke patients with SBP between 140 and less than 220 mmHg to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. A composite primary outcome of death and major disability and secondary outcomes were compared between treatment and control stratified by baseline SBP levels of less than 160, 160-179, and at least 180 mmHg. At 24 h after randomization, differences in SBP reductions were 8.8, 8.6 and 7.8 mmHg between the antihypertensive treatment and control groups among patients with baseline SBP less than 160, 160-179, and at least 180 mmHg, respectively (P < 0.001 among subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups among subgroups. However, there was a significant interaction between antihypertensive treatment and baseline SBP subgroups on death (P = 0.02): odds ratio (95% CI) of 2.42 (0.74-7.89) in patients with baseline SBP less than 60 mmHg and 0.34 (0.11-1.09) in those with baseline SBP at least 180 mmHg. At the 3-month follow-up, the primary and secondary clinical outcomes were not significantly different between the treatment and control groups by baseline SBP levels. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with various baseline SBP levels. Future clinical trials are warranted to test BP-lowering effects in acute ischemic stroke patients by baseline SBP levels. ClinicalTrials.gov Identifier: NCT01840072.

Effects of traditional Chinese patent medicine on essential hypertension: a systematic review.

PubMed

Xiong, Xingjiang; Wang, Pengqian; Zhang, Yuqing; Li, Xiaoke

2015-02-01

Traditional Chinese patent medicine (TCPM) is widely used for essential hypertension (EH) in China. However, there is no critically appraised evidence, such as systematic reviews or meta-analyses, regarding the potential benefits and disadvantages of TCPM to justify their clinical use and recommendation. The aim of this review was to systematically evaluate and meta-analyze the effects of TCPM for EH. Seven databases, the Cochrane Library, PubMed, EMBASE, the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Chinese Biomedical Literature Database, and the Wanfang Database, were searched from their inception to August 2014 for relevant studies that compared one TCPM plus antihypertensive drugs versus antihypertensive drugs alone. The methodological quality of the included trials was assessed using the Cochrane risk-of-bias tool. The primary outcome measures were mortality or progression to severe complications and adverse events. The secondary outcome measures were blood pressure (BP) and quality of life (QOL). Seventy-three trials, which included 8138 patients, on 17 TCPMs were included. In general, the methodological quality was low. Two trials evaluated the effects of TCPMs on mortality and the progression to severe complications after treatment, and no significant difference was identified compared with antihypertensive drugs alone. No severe adverse events were reported. Thirteen TCPMs used in complementary therapy significantly decreased systolic BP by 3.94 to 13.50 mmHg and diastolic BP by 2.28 to 11.25 mmHg. QOL was significantly improved by TCPM plus antihypertensive drugs compared with antihypertensive drugs alone. This systematic review provided the first classification of clinical evidence for the effectiveness of TCPM for EH. The usage of TCPMs for EH was supported by evidence of class level III. As a result of the methodological drawbacks of the included studies, more rigorously designed randomized controlled trials that focus on mortality and cardiovascular events during long-term follow-up are warranted before TCPM can be recommended for hypertensive patients. Two TCPMs, Song ling xue mai kang capsules and Yang xue qing nao granules, should be prioritized for further research.

Cost-effectiveness of Antihypertensive Medication: Exploring Race and Sex Differences Using Data From the REasons for Geographic and Racial Differences in Stroke Study.

PubMed

Tajeu, Gabriel S; Mennemeyer, Stephen; Menachemi, Nir; Weech-Maldonado, Robert; Kilgore, Meredith

2017-06-01

Antihypertensive medication decreases risk of cardiovascular disease (CVD) events in adults with hypertension. Although black adults have higher prevalence of hypertension and worse CVD outcomes compared with whites, limited attention has been given to the cost-effectiveness of antihypertensive medication for blacks. To compare the cost-effectiveness of antihypertensive medication treatment versus no-treatment in white and black adults. We constructed a State Transition Model to assess the costs and quality-adjusted life-years (QALYs) associated with either antihypertensive medication treatment or no-treatment using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study and published literature. CVD events and health states considered in the model included stroke, coronary heart disease, heart failure, chronic kidney disease, and end-stage renal disease. White and black adults with hypertension in the United States, 45 years of age and above. Yearly risk of CVD was determined using REGARDS data and published literature. Antihypertensive medication costs were determined using Medicare claims. Event and health state costs were estimated from published literature. All costs were adjusted to 2012 US dollars. Effectiveness was assessed using QALYs. Antihypertensive medication treatment was cost-saving and increased QALYs compared with no-treatment for white men ($7387; 1.14 QALYs), white women ($7796; 0.89 QALYs), black men ($8400; 1.66 QALYs), and black women ($10,249; 1.79 QALYs). Antihypertensive medication treatment is cost-saving and increases QALYs for all groups considered in the model, particularly among black adults.

Differences in pharmacology and their translation into differences in clinical efficacy--a comparison of the renin angiotensin blocking agents irbesartan and losartan.

PubMed

Bramlage, Peter; Schindler, Christoph

2010-03-01

Guidelines recommend five antihypertensive drug classes, but which particular drug to choose is up to the treating physician. We aimed at an in-depth comparison of two frequently used angiotensin receptor blockers to provide evidence for this decision. Pharmacology of irbesartan and losartan, their blood-pressure-lowering efficacy, their tolerability/safety, end-organ protective effects and economic evaluation. Both drugs differ in their oral bioavailability, potential for food interactions, degree of metabolism, dosing interval, time to peak, volume of distribution and terminal half-life. Irbesartan provides a greater and longer-lasting antihypertensive effect and was determined to be cost effective over losartan in Denmark and Sweden. Irbesartan was more effective in preventing deterioration of kidney function in patients with diabetic nephropathy, being cost effective from a German perspective. There is only one end point trial for either drug in patients with left ventricular hypertrophy, heart failure and atrial fibrillation, but no direct comparison. There is an incremental clinical benefit of irbesartan over losartan in the treatment of hypertension and diabetic nephropathy which can be substantiated by corresponding preclinical study evidence. This has translated into an economic benefit in a number of country-specific evaluations.

Baseline Antihypertensive Drug Count and Patient Response to Hypertension Medication Management.

PubMed

Crowley, Matthew J; Olsen, Maren K; Woolson, Sandra L; King, Heather A; Oddone, Eugene Z; Bosworth, Hayden B

2016-04-01

Telemedicine-based medication management improves hypertension control, but has been evaluated primarily in patients with low antihypertensive drug counts. Its impact on patients taking three or more antihypertensive agents is not well-established. To address this evidence gap, the authors conducted an exploratory analysis of an 18-month, 591-patient trial of telemedicine-based hypertension medication management. Using general linear models, the effect of medication management on blood pressure for patients taking two or fewer antihypertensive agents at study baseline vs those taking three or more was compared. While patients taking two or fewer antihypertensive agents had a significant reduction in systolic blood pressure with medication management, those taking three or more had no such response. The between-subgroup effect difference was statistically significant at 6 months (-6.4 mm Hg [95% confidence interval, -12.2 to -0.6]) and near significant at 18 months (-6.0 mm Hg [95% confidence interval, -12.2 to 0.2]). These findings suggest that baseline antihypertensive drug count may impact how patients respond to hypertension medication management and emphasize the need to study management strategies specifically in patients taking three or more antihypertensive medications. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Pharmacological interventions for hypertension in children.

PubMed

Chaturvedi, Swasti; Lipszyc, Deborah H; Licht, Christoph; Craig, Jonathan C; Parekh, Rulan

2014-02-01

Hypertension is a major risk factor for stroke, coronary artery disease and kidney damage in adults. There is a paucity of data on the long-term sequelae of persistent hypertension in children, but it is known that children with hypertension have evidence of end organ damage and are at risk of hypertension into adulthood. The prevalence of hypertension in children is rising, most likely due to a concurrent rise in obesity rates. In children with hypertension, non-pharmacological measures are often recommended as first-line therapy, but a significant proportion of children will eventually require pharmacological treatment to reduce blood pressure, especially those with evidence of end organ damage at presentation or during follow-up. A systematic review of the effects of antihypertensive agents in children has not previously been conducted. To determine the dose-related effects of different classes of antihypertensive medications, as monotherapy compared to placebo; as combination therapy compared to placebo or a single medication; or in comparisons of various doses within the same class, on systolic or diastolic blood pressure (or both) in children with hypertension. We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), Ovid MEDLINE (1946 to October 2013), Ovid EMBASE (1974 to October 2013) and bibliographic citations. The selection criteria were deliberately broad due to there being few clinical trials in children. We included randomised controlled trials (RCTs) of at least two weeks duration comparing antihypertensive agents either as monotherapy or combination therapy with either placebo or another medication, or comparing different doses of the same medication, in children with hypertension. Hypertension was defined as an average (over a minimum of three readings) systolic or diastolic blood pressure (or both) on the 95(th) percentile or above for age, height and gender.  Two authors independently selected relevant studies, extracted data and assessed risk of bias. We summarised data, where possible, using a random-effects model. Formal assessment of heterogeneity was not possible because of insufficient data. A total of 21 trials evaluated antihypertensive medications of various drug classes in 3454 hypertensive children with periods of follow-up ranging from three to 24 weeks. There were five RCTs comparing an antihypertensive drug directly with placebo, 12 dose-finding trials, two trials comparing calcium channel blockers with angiotensin receptor blockers, one trial comparing a centrally acting alpha blocker with a diuretic and one trial comparing an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker. No randomised trial was identified that evaluated the effectiveness of antihypertensive medications on target end organ damage. The trials were of variable quality and most were funded by pharmaceutical companies.Among the angiotensin receptor blockers, candesartan (one trial, n = 240), when compared to placebo, reduced systolic blood pressure by 6.50 mmHg (95% confidence interval (CI) -9.44 to -3.56) and diastolic blood pressure by 5.50 mmHg (95% CI -9.62 to -1.38) (low-quality evidence). High dose telmisartan (one trial, n = 76), when compared to placebo, reduced systolic blood pressure by -8.50 (95% CI -13.79 to -3.21) but not diastolic blood pressure (-4.80, 95% CI -9.50 to 0.10) (low-quality evidence). Beta blocker (metoprolol, one trial, n = 140), when compared with placebo , significantly reduced systolic blood pressure by 4.20 mmHg (95% CI -8.12 to -0.28) but not diastolic blood pressure (-3.20 mmHg 95% CI -7.12 to 0.72) (low-quality evidence). Beta blocker/diuretic combination (Bisoprolol/hydrochlorothiazide, one trial, n = 94)when compared with placebo , did not result in a significant reduction in systolic blood pressure (-4.0 mmHg, 95% CI -8.99 to -0.19) but did have an effect on diastolic blood pressure (-4.50 mmHg, 95% CI -8.26 to -0.74) (low-quality evidence). Calcium channel blocker (extended-release felodipine,one trial, n = 133) was not effective in reducing systolic blood pressure (-0.62 mmHg, 95% CI -2.97 to 1.73) or diastolic blood pressure (-1.86 mmHg, 95% CI -5.23 to 1.51) when compared with placebo. Further, there was no consistent dose response observed among any of the drug classes. The adverse events associated with the antihypertensive agents were mostly minor and included headaches, dizziness and upper respiratory infections. Overall, there are sparse data informing the use of antihypertensive agents in children, with outcomes reported limited to blood pressure and not end organ damage. The most data are available for candesartan, for which there is low-quality evidence of a modest lowering effect on blood pressure. We did not find evidence of a consistent dose response relationship for escalating doses of angiotensin receptor blockers, calcium channel blockers or angiotensin-converting enzyme inhibitors. All agents appear safe, at least in the short term.

Aliskiren alone or with other antihypertensives in the elderly with borderline and stage 1 hypertension: the APOLLO trial.

PubMed

Teo, Koon K; Pfeffer, Marc; Mancia, Giuseppe; O'Donnell, Martin; Dagenais, Gilles; Diaz, Rafael; Dans, Antonio; Liu, Lisheng; Bosch, Jackie; Joseph, Philip; Copland, Ingrid; Jung, Hyejung; Pogue, Janice; Yusuf, Salim

2014-07-01

We studied the unclear question whether blood pressure (BP) lowering reduces cardiovascular disease (CVD) in elderly individuals with systolic BP <160 mm Hg. We initiated a randomized placebo-controlled stratified 2 × 2 factorial clinical trial evaluating the effects of BP lowering in 11 000 elderly individuals with systolic blood pressure (SBP) between 130 and 159 mm Hg, for 5 years. Following 5-week active run-in, participants were randomized to aliskiren (300 mg) or placebo, and to an additional antihypertensive [hydrochlorothiazide (25 mg) or amlodipine (5 mg)], or their respective placeboes. Study was terminated by sponsor after 1759 subjects (age 72.1 ± 5.2 years, 88% receiving at least one antihypertensive) were randomized and followed for 0.6 year. Study drugs were well tolerated with few serious adverse events during run-in and after randomization, with no significant differences between treatment groups. By design, three levels of BP reductions were achieved, adjusted mean BP reductions of 3.5/1.7 mm Hg (P < 0.001) by aliskiren, 6.8/3.3 mm Hg (P < 0.001) by hydrochlorothiazide or amlodipine, and 10.3/5.0 mm Hg (P < 0.001) by double therapy compared with placebo. Twenty-five major CVD events occurred. Non-significant trends towards fewer CVD events with greater BP reductions are evident: hazard ratios (HR) 0.82 [95% confidence interval (CI): 0.37-1.81] for 3.5 mm Hg SBP reduction; HR 0.45 (95% CI: 0.19-1.04) for 6.8 mm Hg; and HR 0.25 (0.05-1.18) for 10.3 mm Hg reduction for primary composite of CV death, MI, stroke, or significant heart failure. Sizeable reductions in BP, with potential for substantial CVD reduction, can be safely achieved using combinations of BP drugs in the elderly with normal high and Stage 1 hypertension. NCT01259297. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Role of natural herbs in the treatment of hypertension

PubMed Central

Tabassum, Nahida; Ahmad, Feroz

2011-01-01

Hypertension (HTN) is the medical term for high blood pressure. It is dangerous because it makes the heart work too hard and contributes to atherosclerosis (hardening of arteries), besides increasing the risk of heart disease and stroke. HTN can also lead to other conditions such as congestive heart failure, kidney disease, and blindness. Conventional antihypertensives are usually associated with many side effects. About 75 to 80% of the world population use herbal medicines, mainly in developing countries, for primary health care because of their better acceptability with human body and lesser side effects. In the last three decades, a lot of concerted efforts have been channeled into researching the local plants with hypotensive and antihypertensive therapeutic values. The hypotensive and antihypertensive effects of some of these medicinal plants have been validated and others disproved. However, ayurvedic knowledge needs to be coupled with modern medicine and more scientific research needs to be done to verify the effectiveness, and elucidate the safety profile of such herbal remedies for their antihypertensive potential. PMID:22096316

Percutaneous Creation of a Central Iliac Arteriovenous Anastomosis for the Treatment of Arterial Hypertension.

PubMed

Bertog, Stefan C; Sobotka, Nathan A; Sobotka, Paul A; Lobo, Melvin D; Sievert, Kolja; Vaskelyte, Laura; Sievert, Horst; Schmieder, Roland E

2018-03-19

Provision of a summary on the physiologic effects of arteriovenous fistula creation and description of previously published human data on the efficacy of a percutaneously implanted device creating an arteriovenous fistula. Though antihypertensive therapy is effective, some patient's blood pressure remains poorly controlled despite adherence to optimal medical therapy. Moreover, some patients are not compliant with recommended medical therapy due to side effects or personal decision. This has prompted exploration of alternative, device-based antihypertensive therapies including, among others, the percutaneous creation of an arteriovenous fistula. An arteriovenous fistula is accompanied by a number of favorable physiologic changes that may lower blood pressure. These physiologic changes, conduction of the procedure, and previously published human experience are summarized in this review article. The results of a recently published trial comparing arteriovenous fistula creation and standard antihypertensive therapy versus standard antihypertensive therapy alone are summarized. Creation of an arteriovenous fistula is accompanied by a significant blood pressure reduction likely related to a reduction in total arterial resistance, perhaps blood volume reduction, inhibition of the baroreceptor reflex, and release of natriuretic peptides. These findings foster further interest in studying the impact of an arteriovenous fistula and arterial blood pressure. The design of a large randomized trial comparing arteriovenous fistula creation to sham control is outlined.

Prevention of cardiovascular events in elderly people.

PubMed

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

2005-01-01

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

Randomised clinical trial of strategies for improving medication compliance in primary hypertension.

PubMed

Sackett, D L; Haynes, R B; Gibson, E S; Hackett, B C; Taylor, D W; Roberts, R S; Johnson, A L

1975-05-31

230 Canadian steelworkers with hypertension took part in a randomised trial to see if compliance with antihypertensive drug regimens could be improved. For care and follow-up these men were randomly allocated to see either their own family doctors outside working-hours or industrial physicians during work shifts; the same men were randomly allocated to receive or not receive an educational programme aimed at instructing them about hypertension and its treatment. Surprisingly, the convenience of follow-up at work had no effect upon these men's compliance with antihypertensive drug regimens. Similarly, although men receiving health education learned a lot about hypertension, they were not more likely to take their medicine.

The latest development of antihypertensive medication

NASA Astrophysics Data System (ADS)

Nasution, S.; Rey, I.; Effendi-YS, R.

2018-03-01

Hypertension is the most common risk factor for cardiovascular disease, stroke, renal failure, and death. Recent drug monitoring studies found non-adherence to BP lowering therapy in 25% to 65% of patients with apparent treatment-resistant hypertension (TRH). This review focuses on the latest development of antihypertensive medication, such as vasopeptidase inhibitors, aldosterone synthase inhibitors, Soluble Epoxide Hydrolase Inhibitors, agonists of natriuretic peptide receptor, Vasoactive Intestinal Peptide Receptor Agonist, a novel mineralocorticoid receptor antagonist, inhibitors of aminopeptidase A, dopamine β-hydroxylase inhibitor, intestinal Na+/H+ exchanger 3 inhibitor and other agents.

A randomised controlled trial for the evaluation of risk for type 2 diabetes in hypertensive patients receiving thiazide diuretics: Diuretics In the Management of Essential hypertension (DIME) study

PubMed Central

Ueda, Shinichiro; Morimoto, Takeshi; Ando, Shin-ichi; Takishita, Shu-ichi; Kawano, Yuhei; Shimamoto, Kazuaki; Ogihara, Toshio; Saruta, Takao

2014-01-01

Objectives Thiazide diuretics are one of the first choice antihypertensives but not optimally utilised because of concerns regarding their adverse effects on glucose metabolism. The Diuretics In the Management of Essential hypertension (DIME) study was designed, for the first time, to assess the risk for type 2 diabetes mellitus in patients with essential hypertension during antihypertensive treatment with low-dose thiazide diuretics compared to those not treated with diuretics. Design Multicentre, unblinded, pragmatic, randomised, controlled trial with blinded assessment of end points and intention-to-treat analysis that was started in 2004 and finished in 2012. Setting Hypertension clinics at 106 sites in Japan, including general practitioners’ offices and teaching hospitals. Participants Non-diabetic patients with essential hypertension. Interventions Antihypertensive treatment with low-dose thiazide diuretics at 12.5 mg/day of hydrochlorothiazide or equivalent (Diuretics group) or that without thiazide diuretics (No-diuretics group). Main outcome The primary outcome was new onset of type 2 diabetes diagnosed according to WHO criteria and the criteria of Japanese Society of Diabetes. Results 1130 patients were allocated to Diuretics (n=544) or No-diuretics group (n=586). Complete end point information was collected for 1049 participants after a median follow-up of 4.4 years. Diabetes developed in 25 (4.6%) participants in the Diuretics group, as compared with 29 (4.9%) in the No-diuretics group (HR 0.93; 95% CI 0.55 to 1.58; p=0.800). Conclusions Antihypertensive treatment with thiazide diuretics at low doses may not be associated with an increased risk for new onset of type 2 diabetes. This result might suggest safety of use of low doses of thiazide diuretics. Trial registration number ClinicalTrials.gov NCT00131846. PMID:25031188

Accuracy of pharmaceutical advertisements in medical journals.

PubMed

Villanueva, Pilar; Peiró, Salvador; Librero, Julián; Pereiró, Inmaculada

2003-01-04

Because of the effect of the ever-growing evidence-based medicine movement on prescribing behaviour of doctors, the pharmaceutical industry incorporates bibliographical references to clinical trials that endorse their products in their advertisements. We aimed to assess whether the references about efficacy, safety, convenience, or cost of antihypertensive and lipid-lowering drugs included in advertisements supported the promotional claims. We assessed all advertisements for antihypertensive and lipid-lowering drugs published in six Spanish medical journals in 1997 that had at least one bibliographical reference. Two pairs of investigators independently reviewed the advertisements to see whether the studies quoted to endorse the advertising messages supported the corresponding claims. We identified 264 different advertisements for antihypertensive drugs and 23 different advertisements for lipid-lowering drugs. We recorded at least one reference in 31 advertisements in the antihypertensive group and at least one reference in every seven advertisements in the lipid-lowering group, providing a total of 125 promotional claims with references. We could not retrieve 23 (18%) references from monographic works and non-published data on file. 79 (63%) of the 125 references were from journals with a high impact factor; 84 (82%) of the 102 references retrieved were from randomised clinical trials. In 45 claims (44.1%; 95% CI 34.3-54.3) the promotional statement was not supported by the reference, most frequently because the slogan recommended the drug in a patient group other than that assessed in the study. Doctors should be cautious in assessment of advertisements that claim a drug has greater efficacy, safety, or convenience, even though these claims are accompanied by bibliographical references to randomised clinical trials published in reputable medical journals and seem to be evidence-based.

Can we identify response markers to antihypertensive drugs? First results from the IDEAL Trial.

PubMed

Gueyffier, F; Subtil, F; Bejan-Angoulvant, T; Zerbib, Y; Baguet, J P; Boivin, J M; Mercier, A; Leftheriotis, G; Gagnol, J P; Fauvel, J P; Giraud, C; Bricca, G; Maucort-Boulch, D; Erpeldinger, S

2015-01-01

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.

Therapeutic Efficacy and Safety of Traditional Chinese Medicine Classic Herbal Formula Longdanxiegan Decoction for Hypertension: A Systematic Review and Meta-Analysis.

PubMed

Xiong, Xing-Jiang; Yang, Xiao-Chen; Liu, Wei; Duan, Lian; Wang, Peng-Qian; You, Hu; Li, Xiao-Ke; Wang, Shihan

2018-01-01

Background: The traditional Chinese medicine classic herbal formula Longdanxiegan decoction (LDXGD) is widely used for hypertensive patients in China. Objectives: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of LDXGD for hypertension. Methods: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Chinese National Knowledge Infrastructure, and Wanfang Database were searched up to February 7, 2017 for randomized control trials in treating hypertension. Results: Nine trials were identified. Compared with antihypertensive drugs, Longdanxiegan decoction plus antihypertensive drugs (LPAD) significantly improved systolic blood pressure (BP) ( n = 138; MD = -4.82 mmHg; 95% CI: -7.89 to -1.76; P = 0.002), diastolic BP ( n = 138; MD = -2.42 mmHg; 95% CI: -3.22 to -1.62; P < 0.00001), categorical BP ( n = 509; RR: 1.26; 95% CI: 1.17 to 1.36; P < 0.00001), hypertension related symptoms ( n = 509; RR: 1.31; 95% CI: 1.15 to 1.49; P < 0.0001), and heart rate ( n = 138; MD = -2.40 bpm; 95% CI: -4.23 to -0.56; P = 0.01). Beneficial effects but no statistically significant reduction in total cholesterol ( n = 138; MD = -0.11 mmol/l; 95% CI: -0.65 to 0.44; P = 0.71), or triglyceride ( n = 138; MD = -0.20 mmol/l; 95% CI: -0.46 to 0.07; P = 0.14) was observed in LPAD. Compared with antihypertensive drugs, LDXGD used alone significantly improved systolic BP, diastolic BP, and hypertension related symptoms. But there was no difference between LDXGD and antihypertensive drugs on categorical BP ( n = 120; RR: 1.09; 95% CI: 0.96 to 1.23; P = 0.18). The safety of LDXGD were still unclear. Conclusions: Due to poor methodological quality of the included trials, as well as potential reporting bias, our review found no conclusive evidence for the effectiveness of LDXGD in treating hypertension. The potential beneficial effects and safety of LDXGD should be assessed in future properly designed trials.

Calcium channel blockers in hypertension. Is there still a controversy?

PubMed

Izzo, Joseph L

2005-08-01

There are several reasons why no single antihypertensive drug class is ideal in all clinical situations. First, pathophysiologic heterogeneity in hypertension and diversity of mechanisms of antihypertensive drugs dictate that no single drug class can be optimally effective in all subpopulations. Second, sustained blood pressure control generally requires combination therapy to block the reflex stimulation of physiologic mechanisms that attempt to restore blood pressure to pretreatment levels. Third, while effective blood pressure control is more important than choice of initial drug in the prevention of hypertension-related morbidity and mortality, specific drug classes are indicated for optimal treatment of complications of hypertension (e.g. heart failure, kidney disease). Fourth, although antihypertensive drug side effects are uncommon, alternative strategies are required in some patients. Given these principles, past controversies regarding whether calcium channel blockers (CCBs) should be used in the treatment of hypertension become moot. CCBs are extremely effective in lowering blood pressure and in preventing stroke and cardiovascular disease. When additional blood pressure lowering is necessary to meet strict targets, CCBs may be added, even in heart failure or chronic kidney disease, where CCBs alone may not achieve optimal outcomes. Combinations of CCBs with "anti-neurohumoral" drugs such as ACE inhibitors are particularly useful to achieve sustained blood pressure control, reduce adverse effects such as edema, and improve outcomes.

Azilsartan, aliskiren, and combination antihypertensives utilizing renin-angiotensin-aldosterone system antagonists.

PubMed

Lanier, Gregg; Sankholkar, Kedar; Aronow, Wilbert S

2014-01-01

Health care providers managing hypertension (HTN) have a large selection of pharmacologic agents to choose from, including several different classes of drugs and many similar drugs within each class. Antagonism of the renin-angiotensin-aldosterone system has been shown to be very effective for HTN, especially in patients with cardiovascular disease, diabetes, and heart failure. Within this group, there have been 2 new agents recently introduced to the US market and approved by the Food and Drug Administration. It is important for the HTN specialist to be familiar with the merits of these 2 drugs: the angiotensin receptor blocker Edarbi (azilsartan) and the renin inhibitor Tekturna (aliskiren). Additionally, there have been several new, fixed-dose combination antihypertensives introduced to the market since 2006 that use a renin-angiotensin-aldosterone antagonist. Seven of these combine 2 drugs together in a single pill: Edarbyclor (azilsartan/chlorthalidone), Exforge (amlodipine/valsartan), Azor (olmesartan/amlodipine), Twynsta (amlodipine/telmisartan), Tekturna HCT [aliskiren/hydrochlorothiazide (HCTZ)], Valturna (aliskiren/valsartan), Tekamlo (aliskiren/amlodipine). Three triple-drug combination medications have also been introduced recently: Exforge HCT (amlodipine/valsartan/HCTZ), Tribenzor (olmesartan/amlodipine/HCTZ), and Amturnide (aliskiren/amlodipine/hydrocholorothiazide). This review will summarize the trial data and important pharmacologic merits of these 2 new renin-angiotensin-aldosterone antagonists and the advantages of initiating treatment with one of the new fixed-dose, combination drugs approved over the last 5 years.

Effects of aerobic dance training on blood pressure in individuals with uncontrolled hypertension on two antihypertensive drugs: a randomized clinical trial.

PubMed

Maruf, Fatai Adesina; Akinpelu, Aderonke Omobonike; Salako, Babatunde Lawal; Akinyemi, Joshua Odunayo

2016-04-01

There is a dearth of reports on possible additive blood pressure (BP)-reducing effect of aerobic exercise on antihypertensive drug in humans. This study investigated the additive BP-reducing effect of aerobic exercise on BP in individuals with uncontrolled hypertension. In this 12-week double-blind study, 120 new-diagnosed individuals with mild-to-moderate hypertension were randomized to receive coamilozide + 5/10 mg of amlodipine + aerobic dance or coamilozide + 5/10 mg of amlodipine alone. Forty-five and 43 participants in exercise and control groups, respectively, completed the 12-week intervention. Addition of aerobic exercise to antihypertensive drug therapy significantly reduced systolic BP (7.1 mm Hg [95% confidence interval: 5.0, 9.3]; P < .001) and diastolic BP (1.7 mm Hg [95% confidence interval: 0.4, 3.0]; P = .009) at 12 weeks. BP control rate differed significantly between exercise (53.9%) and control (35.3%) groups, P < .001. Postintervention, proportion of participants in exercise group who had their number of antihypertensive drug reduced to one (20.3%) differed from that in control group (11.1%); (χ(2) = 11.0; P = .001). Combination of aerobic dance and antihypertensive drugs reduces number of antihypertensive drugs needed to achieve BP control and enhances BP control in individuals with hypertension on two antihypertensive drugs. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Antihypertensive drugs.

PubMed

Laurent, Stéphane

2017-10-01

Successful treatment of hypertension is possible with limited side effects given the availability of multiple antihypertensive drug classes. This review describes the various pharmacological classes of antihypertensive drugs, under two major aspects: their mechanisms of action and side effects. The mechanism of action is analysed through a pharmacological approach, i.e. the molecular receptor targets, the various sites along the arterial system, and the extra-arterial sites of action, in order to better understand in which type of hypertension a given pharmacological class of antihypertensive drug is most indicated. In addition, side effects are described and explained through their pharmacological mechanisms, in order to better understand their mechanism of occurrence and in which patients drugs are contra-indicated. This review does not address the effectiveness of monotherapies in large randomized clinical trials and combination therapies, since these are the matters of other articles of the present issue. Five major pharmacological classes of antihypertensive drugs are detailed here: beta-blockers, diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium channel blockers. Four additional pharmacological classes are described in a shorter manner: renin inhibitors, alpha-adrenergic receptor blockers, centrally acting agents, and direct acting vasodilators. Copyright © 2017. Published by Elsevier Ltd.

Review: Medicinal plants combating against hypertension: A green antihypertensive approach.

PubMed

Sultana, Sabira; Asif, Hafiz Muhammad

2017-11-01

Hypertension (HTN) or high blood pressure is a medical condition that accounts 9.4 million deaths all over the world every year. It is leading cause of morbidity and mortality worldwide. It increases the risk of cardiovascular diseases, including heart failure, diffuse atherosclerosis, cognitive impairment and dementia. Clinically, synthetic antihypertensive drugs have been used to treat hypertension. However, the efficacy of these drugs is low and also produces side effects which include dry mouth, dizziness, emotional distress, gastrointestinal disturbance, visual disorders etc. These distressing side effects adversely affect health-related quality of life. Therefore, there is a need to search natural, cheaper and non-toxic compound. Plant are widely use in traditional systems of medicine for the treatment of several diseases. About 80% of the world population relies on traditional medicine for primary healthcare. In the last three decades, a lot of research has been done on local medicinal plants for hypotensive and antihypertensive potentials. Plants are the rich source of secondary metabolites which have been found in vivo to have antihypertensive properties. The current study is focused on reviewing the antihypertensive property of medicinal plants and their metabolites. In the current review, we conducted a literature search using Elsevier, Science direct, Springer Link (Springer), Pub Med and Google Scholar. The search included the keywords "plants", "medicinal plants", "plant extracts", cross-referenced with the keywords "hypertension" "antihypertensive activity". The use of plant origin natural compounds as cardio protective and antihypertensive agents is an interesting strategy for discovering bioactive products. Plants are rich in a variety of secondary metabolites, such as flavonoids, alkaloids, tannins and terpenoids. These have been found in vivo to have antihypertensive effects. The present review therefore; stand for a good basis to choose exact molecules belonging to the indicated categories that in the forthcoming future will become useful therapeutic tools.

ALLHAT in perspective: implications to clinical practice and clinical trials.

PubMed

Yusoff, K

2005-06-01

ALLHAT study is the biggest randomized clinical trial in hypertension ever conducted. Its objective was to ompare the efficacy of newer (calcium channel blocker amlodipine and angiotensin-converting enzyme inhibitor inopril) to the older (diuretic chlorthalidone) antihypertensive agents in the treatment of patients with hypertension. After enrolling 42,000 patients who were followed for an average of 4.9 years, ALLHAT did not find significant differences in the primary end-points between these antihypertenive agents. ALLHAT however found significant differences in the secondary end-points such as heart failure and strokes between chlorthalidone and amlodipine or lisinopril. Based on these and on economic reasons, the investigators unequivocally recommended diuretics as the first line therapy for hypertension. Since its publication, ALLHAT has been much discussed, debated A and opined. The choice of drugs for study, the study design, the conduct of the study and the conclusions drawn by the investigators had all been criticised or controversial. Yet ALLHAT has been widely quoted, commented upon or referred to and it has been instrumental in initiating the JNC VII Guidelines. Thus a thorough understanding of ALLHAT is necessary for clinical practice and in designing and evaluating clinical trials in the future. Moving Points: in Medicine will capture the essence of ALLHAT, discusses its implications to clinical trials and explores its possible impact on the practice of medicine in this country.

Angiotensin converting enzyme inhibition in clinical practice. A re-examination of stepped-care: a retrospective and a prospective.

PubMed

Zanchetti, A

1985-01-01

Diuretics have so far enjoyed a prominent position in all stepped-care programs, as the preferred first choice drug in most American schemes or as an alternative first choice drug with respect to beta-blockers in the WHO scheme. Among various reasons for this prominence has been that antihypertensive drugs available until recently all gradually led to sodium and water retention, and therefore required to be combined with a diuretic. This is no longer true: several antihypertensive agents are available now that do not require combination with diuretics, these new agents including not only beta-blockers but also angiotensin-converting enzyme (ACE) inhibitors and calcium entry blockers. Furthermore, some concern about the metabolic effects of diuretics has recently been raised, especially because of the failure to prevent coronary heart disease by the current diuretic-based antihypertensive regimens. Without denying the importance that diuretics have had in the past in making antihypertensive therapy successful and their continuing essential role in treating severe hypertension, it is likely, in my opinion, that in future years diuretics are going to be more often used as agents of second choice, mostly in combination with beta-blockers, ACE inhibitors, and, perhaps, some of the calcium blockers. In conclusion, although opinions of various experts about the sequence of choices between antihypertensive drugs may obviously differ, there is no doubt that the addition of new classes of effective agents, such as the ACE inhibitors and the calcium entry blockers, is making antihypertensive therapy more flexible and more easily suitable to the needs of individual patients.

Rationale for combination therapy in hypertension management: focus on angiotensin receptor blockers and thiazide diuretics.

PubMed

Nash, David T

2007-04-01

Despite recognition that hypertension is a major risk factor for cardiovascular events and mortality, blood pressure control rates remain low in the US population. Reflecting clinical trial results, hypertension management guidelines assert the clinical benefit of achieving current blood pressure goals and indicate that most patients will require 2 or more drugs to reach goal. Well-designed drug combinations counter hypertension via complementary mechanisms that increase antihypertensive efficacy, potentially with lower rates of adverse events than higher dose monotherapy regimens. Lower adverse event rates, in turn, may contribute to greater adherence with treatment. The combination of a low-dose diuretic with agents that block the effects of the renin-angiotensin system (RAS), such as angiotensin receptor blockers, has been found in numerous clinical trials to be highly effective for lowering blood pressure in patients with uncomplicated as well as high-risk hypertension, with a comparable favorable side effect profile compared with monotherapy. Moreover, agents that block the RAS are associated with a lower risk of new-onset diabetes mellitus than other antihypertensive classes. Complementary combinations of antihypertensive agents provide an efficient and effective approach to hypertension management.

A multinational clinical approach to assessing the effectiveness of catheter-based ultrasound renal denervation: The RADIANCE-HTN and REQUIRE clinical study designs.

PubMed

Mauri, Laura; Kario, Kazuomi; Basile, Jan; Daemen, Joost; Davies, Justin; Kirtane, Ajay J; Mahfoud, Felix; Schmieder, Roland E; Weber, Michael; Nanto, Shinsuke; Azizi, Michel

2018-01-01

Catheter-based renal denervation is a new approach to treat hypertension via modulation of the renal sympathetic nerves. Although nonrandomized and small, open-label randomized studies resulted in significant reductions in office blood pressure 6months after renal denervation with monopolar radiofrequency catheters, the first prospective, randomized, sham-controlled study (Symplicity HTN-3) failed to meet its blood pressure efficacy end point. New clinical trials with new catheters have since been designed to address the limitations of earlier studies. Accordingly, the RADIANCE-HTN and REQUIRE studies are multicenter, blinded, randomized, sham-controlled trials designed to assess the blood pressure-lowering efficacy of the ultrasound-based renal denervation system (Paradise) in patients with established hypertension either on or off antihypertensive medications, is designed to evaluate patients in 2 cohorts-SOLO and TRIO, in the United States and Europe. The SOLO cohort includes patients with essential hypertension, at low cardiovascular risk, and either controlled on 1 to 2 antihypertensive medications or uncontrolled on 0 to 2 antihypertensive medications. Patients undergo a 4-week medication washout period before randomization to renal denervation (treatment) or renal angiogram (sham). The TRIO cohort includes patients with hypertension resistant to at least 3 antihypertensive drugs including a diuretic. Patients will be stabilized on a single-pill, triple-antihypertensive-drug combination for 4weeks before randomization to treatment or sham. Reduction in daytime ambulatory systolic blood pressure (primary end point) will be assessed at 2months in both cohorts. A predefined medication escalation protocol, as needed for blood pressure control, is implemented between 2 and 6months in both cohorts by a study staff member blinded to the randomization process. At 6months, daytime ambulatory blood pressure and antihypertensive treatment score will be assessed. REQUIRE is designed to evaluate patients with resistant hypertension on standard of care medication in Japan and Korea. Reduction in 24-hour ambulatory systolic blood pressure will be assessed at 3months (primary end point). Both studies are enrolling patients, and their results are expected in 2018. Copyright © 2017 Elsevier Inc. All rights reserved.

Variation in GP decisions on antihypertensive treatment in oldest-old and frail individuals across 29 countries.

PubMed

Streit, Sven; Verschoor, Marjolein; Rodondi, Nicolas; Bonfim, Daiana; Burman, Robert A; Collins, Claire; Biljana, Gerasimovska Kitanovska; Gintere, Sandra; Gómez Bravo, Raquel; Hoffmann, Kathryn; Iftode, Claudia; Johansen, Kasper L; Kerse, Ngaire; Koskela, Tuomas H; Peštić, Sanda Kreitmayer; Kurpas, Donata; Mallen, Christian D; Maisoneuve, Hubert; Merlo, Christoph; Mueller, Yolanda; Muth, Christiane; Šter, Marija Petek; Petrazzuoli, Ferdinando; Rosemann, Thomas; Sattler, Martin; Švadlenková, Zuzana; Tatsioni, Athina; Thulesius, Hans; Tkachenko, Victoria; Torzsa, Peter; Tsopra, Rosy; Canan, Tuz; Viegas, Rita P A; Vinker, Shlomo; de Waal, Margot W M; Zeller, Andreas; Gussekloo, Jacobijn; Poortvliet, Rosalinde K E

2017-04-20

In oldest-old patients (>80), few trials showed efficacy of treating hypertension and they included mostly the healthiest elderly. The resulting lack of knowledge has led to inconsistent guidelines, mainly based on systolic blood pressure (SBP), cardiovascular disease (CVD) but not on frailty despite the high prevalence in oldest-old. This may lead to variation how General Practitioners (GPs) treat hypertension. Our aim was to investigate treatment variation of GPs in oldest-olds across countries and to identify the role of frailty in that decision. Using a survey, we compared treatment decisions in cases of oldest-old varying in SBP, CVD, and frailty. GPs were asked if they would start antihypertensive treatment in each case. In 2016, we invited GPs in Europe, Brazil, Israel, and New Zealand. We compared the percentage of cases that would be treated per countries. A logistic mixed-effects model was used to derive odds ratio (OR) for frailty with 95% confidence intervals (CI), adjusted for SBP, CVD, and GP characteristics (sex, location and prevalence of oldest-old per GP office, and years of experience). The mixed-effects model was used to account for the multiple assessments per GP. The 29 countries yielded 2543 participating GPs: 52% were female, 51% located in a city, 71% reported a high prevalence of oldest-old in their offices, 38% and had >20 years of experience. Across countries, considerable variation was found in the decision to start antihypertensive treatment in the oldest-old ranging from 34 to 88%. In 24/29 (83%) countries, frailty was associated with GPs' decision not to start treatment even after adjustment for SBP, CVD, and GP characteristics (OR 0.53, 95%CI 0.48-0.59; ORs per country 0.11-1.78). Across countries, we found considerable variation in starting antihypertensive medication in oldest-old. The frail oldest-old had an odds ratio of 0.53 of receiving antihypertensive treatment. Future hypertension trials should also include frail patients to acquire evidence on the efficacy of antihypertensive treatment in oldest-old patients with frailty, with the aim to get evidence-based data for clinical decision-making.

REFRACTORY HYPERTENSION: EVIDENCE OF HEIGHTENED SYMPATHETIC ACTIVITY AS A CAUSE OF ANTIHYPERTENSIVE TREATMENT FAILURE

PubMed Central

Dudenbostel, Tanja; Acelajado, Maria C.; Pisoni, Roberto; Li, Peng; Oparil, Suzanne; Calhoun, David A.

2015-01-01

Refractory hypertension is an extreme phenotype of treatment failure defined as uncontrolled blood pressure (BP) in spite of ≥5 classes of antihypertensive agents, including chlorthalidone and a mineralocorticoid receptor antagonist. A prospective evaluation of possible mechanisms of refractory hypertension has not been done. The goal of this study was to test for evidence of heightened sympathetic tone as indicated by 24-hr urinary (U-) normetanephrine levels, clinic and ambulatory heart rate (HR), HR variability (HRV), arterial stiffness as indexed by pulse wave velocity (PWV), and systemic vascular resistance (SVR) compared to patients with controlled resistant hypertension. Forty-four consecutive patients, 15 with refractory and 29 with controlled resistant hypertension, were evaluated prospectively. Refractory hypertensive patients were younger (48±13.3 vs. 56.5±14.1 years, p=0.038) and more likely female (80.0 vs 51.9 %, p=0.047) compared to patients with controlled resistant hypertension. They also had higher U-normetanephrine levels (464.4±250.2 vs. 309.8±147.6 μg/24h, p=0.03), higher clinic HR (77.8±7.7 vs. 68.8±7.6 bpm, p=0.001) and 24-hr ambulatory HR (77.8±7.7 vs 68.8±7.6, p=0.0018), higher PWV (11.8±2.2 vs. 9.4±1.5 m/s, p=0.009), reduced HRV (4.48 vs. 6.11, p=0.03), and higher SVR (3795±1753 vs. 2382±349 dyne·sec·cm5·m2, p=0.008). These findings are consistent with heightened sympathetic tone being a major contributor to antihypertensive treatment failure and highlight the need for effective sympatholytic therapies in patients with refractory hypertension. PMID:25987662

[German version of a validated instrument to measure the quality of life in patients with hypertension].

PubMed

Chrubasik, C; Himmelberger, D; Kohlmann, T; Chrubasik, S

2012-08-01

The aim of this study was to prepare according to standardised criteria a German version of the validated short instrument for the quality of life in patients suffering from hypertension. This instrument is appropriate for clinical trials investigating the effectiveness of antihypertensive treatments. But also in the daily routine this instrument enables one to identify any impairment of life quality due to antihypertensive treatment as early as possible, especially sexual dysfunction, and to react appropriately with treatment adaptations. © Georg Thieme Verlag KG Stuttgart · New York.

Leveraging prior quantitative knowledge in guiding pediatric drug development: a case study.

PubMed

Jadhav, Pravin R; Zhang, Jialu; Gobburu, Jogarao V S

2009-01-01

The manuscript presents the FDA's focus on leveraging prior knowledge in designing informative pediatric trial through this case study. In developing written request for Drug X, an anti-hypertensive for immediate blood pressure (BP) control, the sponsor and FDA conducted clinical trial simulations (CTS) to design trial with proper sample size and support the choice of dose range. The objective was to effectively use prior knowledge from adult patients for drug X, pediatric data from Corlopam (approved for a similar indication) trial and general experience in developing anti-hypertensive agents. Different scenarios governing the exposure response relationship in the pediatric population were simulated to perturb model assumptions. The choice of scenarios was based on the past observation that pediatric population is less responsive and sensitive compared with adults. The conceptual framework presented here should serve as an example on how the industry and FDA scientists can collaborate in designing the pediatric exclusivity trial. Using CTS, inter-disciplinary scientists with the sponsor and FDA can objectively discuss the choice of dose range, sample size, endpoints and other design elements. These efforts are believed to yield plausible trial design, qrational dosing recommendations and useful labeling information in pediatrics. Published in 2009 by John Wiley & Sons, Ltd.

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial.

PubMed

Webster, Louise M; Myers, Jenny E; Nelson-Piercy, Catherine; Harding, Kate; Cruickshank, J Kennedy; Watt-Coote, Ingrid; Khalil, Asma; Wiesender, Cornelia; Seed, Paul T; Chappell, Lucy C

2017-11-01

Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12 +0 -27 +6 weeks' gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200-1800 mg/d) or nifedipine-modified release (20-80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [-4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [-0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [-2.8 to 3.4 mm Hg], and diastolic: -1.9 mm Hg [-4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (-14.4 to -0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (-6.6 to -0.8 mm Hg; P =0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. URL: https://www.isrctn.com. Unique identifier: ISRCTN40973936. © 2017 American Heart Association, Inc.

Antihypertensive effect of Iranian Crataegus curvisepala Lind.: a randomized, double-blind study.

PubMed

Asgary, S; Naderi, G H; Sadeghi, M; Kelishadi, R; Amiri, M

2004-01-01

The aim of the present study was to investigate the potential antihypertensive effects of extracts of the flavonoid-rich Iranian flower, Crataegus curvisepala Lind., a member of the Rosaceae family. The hydroalcoholic extract of the leaves and flowers were studied in a double-blind, placebo-controlled clinical trial to determine its effects. A total of 92 men and women with primary mild hypertension, aged 40-60 years, were selected and divided randomly into two groups, receiving either hydroalcoholic extract of C. curvisepala Lind. or placebo three times daily for more than 4 months. Blood pressure (BP) was measured each month. Statistical analysis was carried out using Student's t-test. The results obtained showed a significant decrease in both systolic and diastolic BP after 3 months (p < 0.05). C. curvisepala has a time-dependent antihypertensive effect.

Resistant Hypertension: Time to Consider the Best Fifth Anti-Hypertensive Treatment.

PubMed

Pio-Abreu, Andrea; Drager, Luciano F

2018-06-16

Resistant hypertension (RH) is a growing clinical condition worldwide associated with target-organ damage and poor prognosis compared to non-resistant counterparts. The purpose of this review is to perform a critical evaluation of preferable drug choices for managing RH highlighting the evidence that significant proportion of patients remained uncontrolled despite using four anti-hypertensive drugs. Until recently, the fourth drug therapy was main derived from personal opinion or small interventional studies. The recent data derived from two multicentric randomized trials, namely PATHWAY-2 and ReHOT, pointed spironolactone as the preferable fourth drug therapy in patients with confirmed RH as compared to bisoprolol and doxazosin (PATHWAY-2) as well as clonidine (ReHOT). However, significant proportion of patients (especially observed in ReHOT trial that used 24-h ambulatory blood pressure monitoring) did not achieve optimal blood pressure with the fourth drug. This finding underscores the need of new approaches and treatment options in this important research area. The current evidence pointed that significant proportion of RH patients are requiring more than four drugs for controlling BP. This statement is particularly true considering the new criteria proposed by the 2017 Guidelines for diagnosing RH (> 130 × 80 mmHg). New combinations, drugs, or treatments should be tested aiming to reduce the RH burden. Based on the aforementioned multicentric trials, we proposed the first five preferable anti-hypertensive classes in the overall context of RH.

Safety and efficacy of antihypertensive prescription at emergency department discharge.

PubMed

Brody, Aaron; Rahman, Tahsin; Reed, Brian; Millis, Scott; Ference, Brian; Flack, John M; Levy, Phillip D

2015-05-01

Poor blood pressure (BP) control is a primary risk factor for target organ damage in the heart, brain, and kidney. Uncontrolled hypertension is common among emergency department (ED) patients, particularly in underresourced settings, but it is unclear what role ED providers should play in the management of chronic antihypertensive therapy. The objective was to evaluate the safety and efficacy of prescribing antihypertensive therapy from the ED. This was a retrospective study of data pooled from two prospective, longitudinal, randomized controlled trials, both of which enrolled ED patients with asymptomatic hypertension. Antihypertensives were prescribed at emergency physician discretion, and this was not related to randomization arm. Demographic data, BP at screening and randomization visit, and data on adverse effects potentially related to antihypertensive therapy were compiled. Means were compared using Student's t-tests, and proportions were compared using chi-square tests. The effect of antihypertensive therapy on BP control was further analyzed using multivariable regression modeling controlling for age, race, sex, hypertension history, study cohort, and ED BP. Data were abstracted for 217 subjects. The median interval from ED visit to randomization was 12 days. Seventy-six subjects (35%) received one or more prescriptions for antihypertensive therapy. Age, sex, race, hypertension history, and mean duration of hypertension were equivalent between groups. Although mean ED BP was higher among those who received prescriptions, the mean systolic BP (sBP) reduction from ED to randomization was significantly greater (difference = 19 mm Hg, 95% confidence interval = 12 to 26 mm Hg). No patient in either group had an sBP less than 100 mm Hg at randomization. On multiple regression modeling, randomization sBP reduction was independently associated with antihypertensive prescription (p = 0.001). The incidence of adverse effects was equivalent and low in both groups. No new neurological deficits, ischemic events, or life-threatening anaphylactic reactions were reported in either group. Prescription of antihypertensive medication from the ED is associated with significantly lower sBP at short-term outpatient follow-up. Antihypertensive therapy was not associated with an increased incidence of adverse events, and BP reduction did not exceed potentially harmful levels. Initiation of chronic antihypertensive therapy in the ED is safe and effective and may be a reasonable consideration for at-risk populations. © 2015 by the Society for Academic Emergency Medicine.

Molecular targets of antihypertensive peptides: understanding the mechanisms of action based on the pathophysiology of hypertension.

PubMed

Majumder, Kaustav; Wu, Jianping

2014-12-24

There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

Arterial hypertension in the female world: pathophysiology and therapy.

PubMed

Cadeddu, Christian; Franconi, Flavia; Cassisa, Laura; Campesi, Ilaria; Pepe, Alessia; Cugusi, Lucia; Maffei, Silvia; Gallina, Sabina; Sciomer, Susanna; Mercuro, Giuseppe

2016-04-01

Hypertension is a major risk factor for cardiovascular disease and outcomes in women, and antihypertensive therapy is not always successful in achieving control over the blood pressure (BP). Nonoptimal control of BP remains a crucial risk factor for cardiovascular mortality, and in women, it could be related to sex-specific factors. Historically, women have been under-represented in clinical trials; therefore, the benefits of clinical outcomes and the safety profiles of antihypertensive therapies have been studied less extensively in women. The reasons for the sex differences in BP levels are multifactorial, implying different roles of the sex hormones, the renin-angiotensin system, sympathetic activity, and arterial stiffness. A complete understanding of the pathophysiological features of these differences requires further investigation.Nevertheless, the prevalence of the use of antihypertensive agents is higher among middle-aged women than among men. Notably, in the United States, hypertensive women use more diuretics and angiotensin receptor blockers than men, whereas hypertensive men more often receive beta-blockers, calcium channel antagonists, or inhibitors of angiotensin-converting enzyme. To date, the explanations for these sex differences in the consumption of antihypertensive drugs remain unknown.

Molecular Targets of Antihypertensive Peptides: Understanding the Mechanisms of Action Based on the Pathophysiology of Hypertension

PubMed Central

Majumder, Kaustav; Wu, Jianping

2014-01-01

There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides. PMID:25547491

A sudden death risk score specifically for hypertension: based on 25 648 individual patient data from six randomized controlled trials.

PubMed

Le, Hai-Ha; Subtil, Fabien; Cerou, Marc; Marchant, Ivanny; Al-Gobari, Muaamar; Fall, Mor; Mimouni, Yanis; Kassaï, Behrouz; Lindholm, Lars; Thijs, Lutgarde; Gueyffier, François

2017-11-01

To construct a sudden death risk score specifically for hypertension (HYSUD) patients with or without cardiovascular history. Data were collected from six randomized controlled trials of antihypertensive treatments with 8044 women and 17 604 men differing in age ranges and blood pressure eligibility criteria. In total, 345 sudden deaths (1.35%) occurred during a mean follow-up of 5.16 years. Risk factors of sudden death were examined using a multivariable Cox proportional hazards model adjusted on trials. The model was transformed to an integer system, with points added for each factor according to its association with sudden death risk. Antihypertensive treatment was not associated with a reduction of the sudden death risk and had no interaction with other factors, allowing model development on both treatment and placebo groups. A risk score of sudden death in 5 years was built with seven significant risk factors: age, sex, SBP, serum total cholesterol, cigarette smoking, diabetes, and history of myocardial infarction. In terms of discrimination performance, HYSUD model was adequate with areas under the receiver operating characteristic curve of 77.74% (confidence interval 95%, 74.13-81.35) for the derivation set, of 77.46% (74.09-80.83) for the validation set, and of 79.17% (75.94-82.40) for the whole population. Our work provides a simple risk-scoring system for sudden death prediction in hypertension, using individual data from six randomized controlled trials of antihypertensive treatments. HYSUD score could help assessing a hypertensive individual's risk of sudden death and optimizing preventive therapeutic strategies for these patients.

Effect of Antihypertensive Medications on the Severity of Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis

PubMed Central

Khurshid, Kiran; Yabes, Jonathan; Weiss, Patricia M.; Dharia, Sushma; Brown, Lee; Unruh, Mark; Jhamb, Manisha

2016-01-01

Study Objectives: Obstructive sleep apnea (OSA) is an independent risk factor for hypertension (HTN). Increasing evidence from animal and human studies suggests that HTN exacerbates OSA. We performed a systematic review and meta-analysis of studies evaluating the effect of anti-hypertensive medications on the severity of OSA. Methods: A literature search of PubMed and Embase was done using search concepts of OSA, HTN, and drug classes used to treat HTN. Studies that reported changes in the severity of OSA objectively by using apnea-hypopnea index (AHI) or respiratory disturbance index (RDI) were included. Pooled mean difference estimates were calculated. Tests for heterogeneity, publication bias, and subgroup sensitivity analysis were conducted. Results: Of 27,376 studies screened, only 11 met inclusion criteria, including 5 randomized controlled trials and 6 single-arm prospective trials. The pooled mean difference estimate (95% confidence interval [CI]), based on a random-effects model, was −5.69 (95% CI −10.74 to −0.65), consistent with an overall decrease in AHI or RDI attributable to antihypertensive medications. The effect size was even more pronounced, −14.52 (95% CI −25.65 to −3.39), when only studies using diuretics were analyzed. There was no significant heterogeneity or publication bias among the studies. Meta-regression indicated neither age, baseline AHI, nor change in systolic/diastolic blood pressure influenced the results. Conclusions: Collectively, findings from these relatively small, short-term studies tend to support the contention that treatment with antihypertensive agents confers a statistically significant, albeit small, reduction in the severity of OSA, which may be more pronounced with the use of diuretics. Citation: Khurshid K, Yabes J, Weiss PM, Dharia S, Brown L, Unruh M, Jhamb M. Effect of antihypertensive medications on the severity of obstructive sleep apnea: a systematic review and meta-analysis. J Clin Sleep Med 2016;12(8):1143–1151. PMID:27397663

Blood pressure as a therapeutic target in stroke.

PubMed

Armario, Pedro; de la Sierra, Alejandro

2009-01-01

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

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

PubMed

Armario, Pedro; de la Sierra, Alejandro

2009-06-01

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

Aldosterone, cognitive function, and cerebral hemodynamics in hypertension and antihypertensive therapy.

PubMed

Hajjar, Ihab; Hart, Meaghan; Mack, Wendy; Lipsitz, Lewis A

2015-03-01

Animal studies suggest that the renin-angiotensin-aldosterone system is involved in neurocognitive function and the response to antihypertensive therapy. We investigated the impact of circulating aldosterone and renin activity on cognition and cerebral hemodynamics at baseline and after antihypertensive therapy for 1 year. Participants were older adults (n = 47; mean age = 71 years) enrolled in a clinical trial. Routine antihypertensive medications were replaced with the study regimen to achieve a blood pressure <140/90 mm Hg. Executive function, memory, cerebral hemodynamics (blood flow velocity), CO2 vasoreactivity (measured using transcranial Doppler ultrasonography), plasma renin activity, and aldosterone were measured at baseline and at 6 and 12 months after the initiation of treatment. At baseline, higher levels of circulating aldosterone were associated with lower blood flow velocity (β = -0.02; P = 0.03), lower CO2 vasoreactivity (β = -0.11; P = 0.007), and decreased autoregulation abilities (β = -0.09; P = 0.01). Those with higher levels of aldosterone at baseline demonstrated the greatest improvement in executive function (P = 0.014 for the aldosterone effect) and in CO2 vasoreactivity (P = 0.026 for the aldosterone effect) after 12 months of lowering blood pressure (<140/90 mm Hg). Plasma renin activity was not associated with any of the measures. Higher levels of aldosterone may be associated with decreased cerebrovascular function in hypertension. Those with higher aldosterone levels may benefit the most from lowering blood pressure. The role of aldosterone in brain health warrants further investigation in a larger trial. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Aldosterone, Cognitive Function, and Cerebral Hemodynamics in Hypertension and Antihypertensive Therapy

PubMed Central

Hart, Meaghan; Mack, Wendy; Lipsitz, Lewis A.

2015-01-01

BACKGROUND Animal studies suggest that the renin–angiotensin–aldosterone system is involved in neurocognitive function and the response to antihypertensive therapy. We investigated the impact of circulating aldosterone and renin activity on cognition and cerebral hemodynamics at baseline and after antihypertensive therapy for 1 year. METHODS Participants were older adults (n = 47; mean age = 71 years) enrolled in a clinical trial. Routine antihypertensive medications were replaced with the study regimen to achieve a blood pressure <140/90mm Hg. Executive function, memory, cerebral hemodynamics (blood flow velocity), CO2 vasoreactivity (measured using transcranial Doppler ultrasonography), plasma renin activity, and aldosterone were measured at baseline and at 6 and 12 months after the initiation of treatment. RESULTS At baseline, higher levels of circulating aldosterone were associated with lower blood flow velocity (β = −0.02; P = 0.03), lower CO2 vasoreactivity (β = −0.11; P = 0.007), and decreased autoregulation abilities (β = −0.09; P = 0.01). Those with higher levels of aldosterone at baseline demonstrated the greatest improvement in executive function (P = 0.014 for the aldosterone effect) and in CO2 vasoreactivity (P = 0.026 for the aldosterone effect) after 12 months of lowering blood pressure (<140/90mm Hg). Plasma renin activity was not associated with any of the measures. CONCLUSIONS Higher levels of aldosterone may be associated with decreased cerebrovascular function in hypertension. Those with higher aldosterone levels may benefit the most from lowering blood pressure. The role of aldosterone in brain health warrants further investigation in a larger trial. PMID:25213687

Qigong for hypertension: a systematic review.

PubMed

Xiong, Xingjiang; Wang, Pengqian; Li, Xiaoke; Zhang, Yuqing

2015-01-01

The purpose of this review was to evaluate the efficacy and safety of qigong for hypertension.A systematic literature search was performed in 7 databases from their respective inceptions until April 2014, including the Cochrane Library, EMBASE, PubMed, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, Wanfang database, and Chinese National Knowledge Infrastructure. Randomized controlled trials of qigong as either monotherapy or adjunctive therapy with antihypertensive drugs versus no intervention, exercise, or antihypertensive drugs for hypertension were identified. The risk of bias was assessed using the tool described in Cochrane Handbook for Systematic Review of Interventions, version 5.1.0.Twenty trials containing 2349 hypertensive patients were included in the meta-analysis. The risk of bias was generally high. Compared with no intervention, qigong significantly reduced systolic blood pressure (SBP) (weighted mean difference [WMD] = -17.40 mm Hg, 95% confidence interval [CI] -21.06 to -13.74, P < 0.00001) and diastolic blood pressure (DBP) (WMD = -10.15 mm Hg, 95% CI -13.99 to -6.30, P < 0.00001). Qigong was inferior to exercise in decreasing SBP (WMD = 6.51 mm Hg, 95% CI 2.81 to 10.21, P = 0.0006), but no significant difference between the effects of qigong and exercise on DBP (WMD = 0.67 mm Hg, 95% CI -1.39 to 2.73, P = 0.52) was identified. Compared with antihypertensive drugs, qigong produced a clinically meaningful but not statistically significant reduction in SBP (WMD = -7.91 mm Hg, 95% CI -16.81 to 1.00, P = 0.08), but appeared to be more effective in lowering DBP (WMD = -6.08 mm Hg, 95% CI -9.58 to -2.58, P = 0.0007). Qigong plus antihypertensive drugs significantly lowered both SBP (WMD = -11.99 mm Hg, 95% CI -15.59 to -8.39, P < 0.00001) and DBP (WMD = -5.28 mm Hg, 95% CI, -8.13 to -2.42, P = 0.0003) compared with antihypertensive drugs alone. No serious adverse events were reported.The meta-analysis suggests that qigong is an effective therapy for hypertension. However, more rigorously designed randomized controlled trials with long-term follow-up focusing on hard clinical outcomes are required to confirm the results.

Summer syncope syndrome.

PubMed

Huang, Jennifer Juxiang; Sharda, Natasha; Riaz, Irbaz Bin; Alpert, Joseph S

2014-08-01

Antihypertensive therapy is associated with significant relative risk reductions in the incidence of heart failure, myocardial infarction, and stroke. However, a common adverse reaction to antihypertensive therapy is orthostatic hypotension, dehydration, and syncope. We propose that continued use of antihypertensive medications at the same dosage during the dry summer months in patients living in the Sonoran desert leads to an increase in syncopal episodes. All hypertensive patients who were treated with medications and admitted with International Classification of Diseases, 9th Revision code diagnosis of syncope were included. They were defined as "cases" if they presented during the summer months (May to September 2012) and "controls" if they presented during the winter months (November 2012 to March 2013). The primary outcome measure was the presence of clinical dehydration. The statistical significance was determined using the 2-sided Fisher exact test. A total of 496 patients with an International Classification of Diseases, 9th Revision code diagnosis of syncope were screened, and 179 patients were included in the final analysis. In patients taking antihypertensive medications, there were a significantly higher number of cases of syncope secondary to dehydration or orthostatic hypotension during the summer months (45%) compared with the winter months (26%) (P = .01). The incidence of syncope was significantly higher in older patients (63%) compared with younger individuals (37%) during the summer months. The incidence of syncope increases during the summer months among people who reside in a dry desert climate and who are taking antihypertensive medications. On the basis of our findings, we describe an easily preventable condition that we define as the "Summer Syncope Syndrome." We recommend judicious reduction of antihypertensive therapy in patients residing in a hot and dry climate, particularly during the summer months. Copyright © 2014 Elsevier Inc. All rights reserved.

Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy.

PubMed

Bakris, George; Burgess, Ellen; Weir, Matthew; Davidai, Giora; Koval, Stephen

2008-08-01

In patients with diabetic nephropathy, lowering blood pressure and reducing proteinuria by over 30% correlates with a slower progression to kidney failure. We compared two different angiotensin receptor-blockers in a double blind, prospective trial of 860 patients with type 2 diabetes whose blood pressure levels was over 130/80 mmHg or who were receiving antihypertensive medication(s) and who had a morning spot urinary protein to creatinine ratio of 700 or more. Patients were randomized to telmisartan (a highly lipophilic agent with a long half-life) or losartan (with low lipophilicity and short half-life). The primary endpoint was the difference in the urinary albumin to creatinine ratio between the groups at 52 weeks. The geometric coefficient of variation and the mean of the urinary albumin to creatinine ratio fell in both groups at 52 weeks but both were significantly greater for the telmisartan compared to the losartan cohort. Mean systolic blood pressure reductions were not significantly different between groups at trial end. We conclude that telmisartan is superior to losartan in reducing proteinuria in hypertensive patients with diabetic nephropathy, despite a similar reduction in blood pressure.

Summer syncope syndrome redux.

PubMed

Huang, Jennifer Juxiang; Desai, Chirag; Singh, Nirmal; Sharda, Natasha; Fernandes, Aaron; Riaz, Irbaz Bin; Alpert, Joseph S

2015-10-01

While antihypertensive therapy is known to reduce the risk for heart failure, myocardial infarction, and stroke, it can often cause orthostatic hypotension and syncope, especially in the setting of polypharmacy and possibly, a hot and dry climate. The objective of the present study was to investigate whether the results of our prior study involving continued use of antihypertensive drugs at the same dosage in the summer as in the winter months for patients living in the Sonoran desert resulted in an increase in syncopal episodes during the hot summer months. All hypertensive patients who were treated with medications and admitted with International Classification of Diseases, 9th Revision code diagnosis of syncope were included. This is a 3-year retrospective chart review study. They were defined as "cases" if they presented during the summer months (May to September) and "controls" if they presented during the winter months (November to March). The primary outcome measure was the presence of clinical dehydration. The statistical significance was determined using the 2-sided Fisher's exact test. A total of 834 patients with an International Classification of Diseases, 9th Revision code diagnosis of syncope were screened: 477 in the summer months and 357 in the winter months. In patients taking antihypertensive medications, there was a significantly higher number of cases of syncope secondary to dehydration during the summer months (40.5%) compared with the winter months (29%) (P = .04). No difference was observed in the type of antihypertensive medication used and syncope rate. The number of antihypertensives used did not increase the cases of syncope in either summer or winter. An increased number of syncope events was observed in the summer months among people who reside in a dry desert climate and who are taking antihypertensive medications. The data confirm our earlier observations that demonstrated a greater number of cases of syncope among people who reside in a dry desert climate who were taking antihypertensive medications during summer months. We recommend judicious reduction of antihypertensive therapy in patients residing in a hot and dry climate, particularly during the summer months. Copyright © 2015 Elsevier Inc. All rights reserved.

Therapeutic Inertia and Treatment Intensification.

PubMed

Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

2018-01-29

This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

PubMed

Reboussin, David M; Allen, Norrina B; Griswold, Michael E; Guallar, Eliseo; Hong, Yuling; Lackland, Daniel T; Miller, Edgar Pete R; Polonsky, Tamar; Thompson-Paul, Angela M; Vupputuri, Suma

2018-06-01

To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of <130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (ie, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome. © 2017 by the American College of Cardiology Foundation and the American Heart Association, Inc.

New horizons: the management of hypertension in people with dementia

PubMed Central

Harrison, Jennifer Kirsty; Van Der Wardt, Veronika; Conroy, Simon Paul; Stott, David J.; Dening, Tom; Gordon, Adam Lee; Logan, Pip; Welsh, Tomas James; Taggar, Jaspal; Harwood, Rowan; Gladman, John R. F.

2016-01-01

Abstract The optimal management of hypertension in people with dementia is uncertain. This review explores if people with dementia experience greater adverse effects from antihypertensive medications, if cognitive function is protected or worsened by controlling blood pressure (BP) and if there are subgroups of people with dementia for whom antihypertensive therapy is more likely to be harmful. Robust evidence is scant, trials of antihypertensive medications have generally excluded those with dementia. Observational data show changes in risk association over the life course, with high BP being a risk factor for cognitive decline in mid-life, while low BP is predictive in later life. It is therefore possible that excessive BP lowering in older people with dementia might harm cognition. From the existing literature, there is no direct evidence of benefit or harm from treating hypertension in people with dementia. So what practical steps can the clinician take? Assess capacity, establish patient preferences when making treatment decisions, use ambulatory monitoring to thoroughly assess BP, individualise and consider deprescribing where side effects (e.g. hypotension) outweigh the benefits. Future research might include pragmatic randomised trials of targeted deprescribing, which include patient-centred outcome measures to help support decision-making and studies to address mechanistic uncertainties. PMID:27836926

Male Infertility during Antihypertensive Therapy: Are We Addressing Correctly The Problem?

PubMed

Laganà, Antonio Simone; Vitale, Salvatore Giovanni; Iaconianni, Paola; Gatti, Simona; Padula, Francesco

2016-01-01

Male fertility significantly decreased in the last 50 years, as showed in several studies reporting a reduction of sperm counts per ml in the seminal fluid. Several "acute" pharmacological treatments, as antibiotics, could cause subclinical and temporary reduction of male fertility; conversely, long-term medical treatment may severely affect male fertility, although this effect could be considered transient in most of the cases. Thus, nowadays, several long-term pharmacological treatments may represent a clinical challenge. The association between several kind of antihypertensive drugs and reduction of male fertility has been showed in the mouse model, although the modification(s) which may alter this fine-regulated machinery are still far to be elucidated. Furthermore, well-designed observational studies and randomized controlled trials are needed to accurately define this association in human model, meaning a narrative overview synthesizing the findings of literature retrieved from searches of computerized databases. We strongly solicit future human studies (both observational and randomized clinical trials) on large cohorts with adequate statistical power which may clarify this possible association and the effects (reversible or permanent) of each drug. Furthermore, we suggest a close collaboration between general practitioners, cardiologists, and andrologists in order to choose the most appropriate antihypertensive therapy considering also patient's reproductive desire and possible risk for his fertility.

Gender Differences in Epidemiology, Pathophysiology, and Treatment of Hypertension.

PubMed

Di Giosia, Paolo; Giorgini, Paolo; Stamerra, Cosimo Andrea; Petrarca, Marco; Ferri, Claudio; Sahebkar, Amirhossein

2018-02-14

This review aims to examine gender differences in both the epidemiology and pathophysiology of hypertension and to explore gender peculiarities on the effects of antihypertensive agents in decreasing BP and CV events. Men and women differ in prevalence, awareness, and control rate of hypertension in an age-dependent manner. Studies suggest that sex hormones changes play a pivotal role in the pathophysiology of hypertension in postmenopausal women. Estrogens influence the vascular system inducing vasodilatation, inhibiting vascular remodeling processes, and modulating the renin-angiotensin aldosterone system and the sympathetic system. This leads to a protective effect on arterial stiffness during reproductive age that is dramatically reversed after menopause. Data on the efficacy of antihypertensive therapy between genders are conflicting, and the underrepresentation of aged women in large clinical trials could influence the results. Therefore, further clinical research is needed to uncover potential gender differences in hypertension to promote the development of a gender-oriented approach to antihypertensive treatment.

Angiotensin-converting enzyme inhibitor use by older adults is associated with greater functional responses to exercise.

PubMed

Buford, Thomas W; Manini, Todd M; Hsu, Fang-Chi; Cesari, Matteo; Anton, Stephen D; Nayfield, Susan; Stafford, Randall S; Church, Timothy S; Pahor, Marco; Carter, Christy S

2012-07-01

To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training. Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability. Four academic research centers within the United States. Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers. A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA). Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)). Physical activity significantly improved the adjusted walking speed of ACEi users (P < .001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P < .001) and of persons who used other antihypertensive drugs (P = .005) but not of antihypertensive nonusers (P = .91).The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively). For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

Angiotensin-Converting Enzyme Inhibitor Use by Older Adults Is Associated with Greater Functional Responses to Exercise

PubMed Central

Buford, Thomas W.; Manini, Todd M.; Hsu, Fang-Chi; Cesari, Matteo; Anton, Stephen D.; Nayfield, Susan; Stafford, Randall S.; Church, Timothy S.; Pahor, Marco; Carter, Christy S.

2013-01-01

OBJECTIVES To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training. DESIGN Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability. SETTING Four academic research centers within the United States. PARTICIPANTS Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers. INTERVENTION A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA). MEASUREMENTS Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)). RESULTS Physical activity significantly improved the adjusted walking speed of ACEi users (P < .001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P < .001) and of persons who used other antihypertensive drugs (P = .005) but not of antihypertensive nonusers (P = .91). The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively). CONCLUSION For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers. PMID:22726232

A prospective study on pulse wave velocity (PWV) and response to anti-hypertensive treatments: PWV determines BP control.

PubMed

Zheng, Meili; Huo, Yong; Wang, Xiaobin; Xu, Xin; Qin, Xianhui; Tang, Genfu; Xing, Houxun; Fan, Fangfang; Li, Jianping; Zhang, Yan; Wang, Binyan; Xu, Xiping; Yang, Xinchun; Chen, Yundai; Qian, Geng

2015-01-15

Recent data indicate that hypertension is not well controlled in many populations throughout the world. The factors that influence individual response to anti-hypertensive treatment need to be clarified. Pulse wave velocity (PWV), as a marker of arterial stiffness, has been demonstrated to have important relationships with BP progression; however, little information is available on the role of PWV in blood pressure (BP) control. We aimed to assess BP control during the run-in treatment period in the China Stroke Primary Prevention Trial (CSPPT). These analyses included a total of 3056 treated hypertensive subjects (age: 59.6±7.5years, male/female 1339/1717) with PWV measured at baseline. The average BP at enrollment was 166/95mmHg, and declined to 141/85mmHg after short-term antihypertensive treatment (a median follow-up of 20days). There was an inverse relationship between PWV level and BP reduction during the treatment, most notably for systolic BP (with estimated coefficients of -9.01 (P<0.001) for the top quartile, as compared to the bottom quartile). The association did not differ significantly by gender or types of antihypertensive drugs. Factors related to smaller BP decline were low baseline BP, high baseline PWV, high body mass index, high creatinine, use of fewer types of antihypertensive drug, high heart rate (only for SBP), high homocysteine and low age (only for DBP). PWV appears to be an independent determinant of individual response to anti-hypertensive treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Circulatory therapeutics: use of antihypertensive agents and their effects on the vasculature

PubMed Central

Schiffrin, Ernesto L

2010-01-01

Abstract This review addresses the use of the different antihypertensive agents currently available and some in development, and their effects on the vasculature. The different classes of agents used in the treatment of hypertension, and the results of recent large clinical trials, dosing protocols and adverse effects are first briefly summarized. The consequences on blood vessels of the use of antihypertensive drugs and the differential effects on the biology of large and small arteries resulting in modulation of vascular remodelling and dysfunction in hypertensive patients are then described. Large elastic conduit arteries exhibit outward hypertrophic remodelling and increased stiffness, which contributes to raise systolic blood pressure and afterload on the heart. Small resistance arteries undergo eutrophic or hypertrophic inward remodelling, and impair tissue perfusion. By these mechanisms both large and small arteries may contribute to trigger cardiovascular events. Some antihypertensive agents correct these changes, which could contribute to improved outcome. The mechanisms that at the level of the vascular wall lead to remodelling and can be beneficially affected by antihypertensive agents will also be addressed. These include vasoconstriction, growth and inflammation. The molecular pathways contributing to growth and inflammation will be summarily described. Further identification of these signalling pathways should allow identification of novel targets leading to development of new and improved medications for the treatment of hypertension and cardiovascular disease. PMID:20345850

Electrocardiographic measures of left ventricular hypertrophy in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

PubMed

Ernst, Michael E; Davis, Barry R; Soliman, Elsayed Z; Prineas, Ronald J; Okin, Peter M; Ghosh, Alokananda; Cushman, William C; Einhorn, Paula T; Oparil, Suzanne; Grimm, Richard H

2016-12-01

Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up electrocardiographies in 26,376 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH was examined using continuous and categorical classifications of Cornell voltage. At 2 and 4 years, prevalence of LVH in the C group (5.57%; 6.14%) was not statistically different from A group (2 years: 5.47%; P = .806, 4 years: 6.54%; P = .857) or L group (2 years: 5.64%; P = .857, 4 years: 6.50%; P = .430). Incident LVH followed similarly, with no difference at 2 years for C (2.99%) compared to A (2.57%; P = .173) or L (3.16%; P = .605) and at 4 years (C = 3.52%, A = 3.29%, L = 3.71%; P = .521 C vs. A, P = .618 C vs. L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2 years = +3 to -27 μV, analysis of variance P = .8612; 4 years = +10 to -17 μV, analysis of variance P = .9692). We conclude that risk reductions associated with C treatment in secondary end points of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial cannot be attributed to differential improvements in electrocardiography LVH. Copyright © 2016 American Society of Hypertension. All rights reserved.

Stress management versus lifestyle modification on systolic hypertension and medication elimination: a randomized trial.

PubMed

Dusek, Jeffery A; Hibberd, Patricia L; Buczynski, Beverly; Chang, Bei-Hung; Dusek, Kathryn C; Johnston, Jennifer M; Wohlhueter, Ann L; Benson, Herbert; Zusman, Randall M

2008-03-01

Isolated systolic hypertension is common in the elderly, but decreasing systolic blood pressure (SBP) without lowering diastolic blood pressure (DBP) remains a therapeutic challenge. Although stress management training, in particular eliciting the relaxation response, reduces essential hypertension its efficacy in treating isolated systolic hypertension has not been evaluated. We conducted a double-blind, randomized trial comparing 8 weeks of stress management, specifically relaxation response training (61 patients), versus lifestyle modification (control, 61 patients). Inclusion criteria were >or=55 years, SBP 140-159 mm Hg, DBP <90 mm Hg, and at least two antihypertensive medications. The primary outcome measure was change in SBP after 8 weeks. Patients who achieved SBP <140 mm Hg and >or=5 mm Hg reduction in SBP were eligible for 8 additional weeks of training with supervised medication elimination. SBP decreased 9.4 (standard deviation [SD] 11.4) and 8.8 (SD 13.0) mm Hg in relaxation response and control groups, respectively (both ps <0.0001) without group difference (p=0.75). DBP decreased 1.5 (SD 6.2) and 2.4 (SD 6.9) mm Hg (p=0.05 and 0.01, respectively) without group difference (p=0.48). Forty-four (44) in the relaxation response group and 36 in the control group were eligible for supervised antihypertensive medication elimination. After controlling for differences in characteristics at the start of medication elimination, patients in the relaxation response group were more likely to successfully eliminate an antihypertensive medication (odds ratio 4.3, 95% confidence interval 1.2-15.9, p=0.03). Although both groups had similar reductions in SBP, significantly more participants in the relaxation response group eliminated an antihypertensive medication while maintaining adequate blood pressure control.

Effects of Bariatric Surgery in Obese Patients With Hypertension

PubMed Central

Bersch-Ferreira, Angela Cristine; Santucci, Eliana Vieira; Oliveira, Juliana Dantas; Torreglosa, Camila Ragne; Bueno, Priscila Torres; Frayha, Julia Caldas; Santos, Renato Nakagawa; Damiani, Lucas Petri; Noujaim, Patricia Malvina; Halpern, Helio; Monteiro, Frederico L.J.; Cohen, Ricardo Vitor; Uchoa, Carlos H.; de Souza, Marcio Gonçalves; Amodeo, Celso; Bortolotto, Luiz; Ikeoka, Dimas; Drager, Luciano F.; Cavalcanti, Alexandre Biasi; Berwanger, Otavio

2018-01-01

Background: Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution. Randomized trials designed to assess the impact of bariatric surgery in patients with obesity and hypertension are needed. Methods: In this randomized, single-center, nonblinded trial, we included patients with hypertension (using ≥2 medications at maximum doses or >2 at moderate doses) and a body mass index between 30.0 and 39.9 kg/m2. Patients were randomized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone. The primary end point was reduction of ≥30% of the total number of antihypertensive medications while maintaining systolic and diastolic blood pressure <140 mm Hg and 90 mm Hg, respectively, at 12 months. Results: We included 100 patients (70% female, mean age 43.8±9.2 years, mean body mass index 36.9±2.7 kg/m2), and 96% completed follow-up. Reduction of ≥30% of the total number of antihypertensive medications while maintaining controlled blood pressure occurred in 41 of 49 patients from the gastric bypass group (83.7%) compared with 6 of 47 patients (12.8%) from the control group with a rate ratio of 6.6 (95% confidence interval, 3.1–14.0; P<0.001). Remission of hypertension was present in 25 of 49 (51%) and 22 of 48 (45.8%) patients randomized to gastric bypass, considering office and 24-hour ambulatory blood pressure monitoring, respectively, whereas no patient submitted to medical therapy was free of antihypertensive drugs at 12 months. A post hoc analysis for the primary end point considering the SPRINT (Systolic Blood Pressure Intervention Trial) target reached consistent results, with a rate ratio of 3.8 (95% confidence interval, 1.4–10.6; P=0.005). Eleven patients (22.4%) from the gastric bypass group and none in the control group were able to achieve SPRINT levels without antihypertensives. Waist circumference, body mass index, fasting plasma glucose, glycohemoglobin, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and 10-year Framingham risk score were lower in the gastric bypass than in the control group. Conclusions: Bariatric surgery represents an effective strategy for blood pressure control in a broad population of patients with obesity and hypertension. Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT01784848. PMID:29133606

Telemonitoring and/or self-monitoring of blood pressure in hypertension (TASMINH4): protocol for a randomised controlled trial.

PubMed

Franssen, Marloes; Farmer, Andrew; Grant, Sabrina; Greenfield, Sheila; Heneghan, Carl; Hobbs, Richard; Hodgkinson, James; Jowett, Susan; Mant, Jonathan; Martin, Una; Milner, Siobhan; Monahan, Mark; Ogburn, Emma; Perera-Salazar, Rafael; Schwartz, Claire; Yu, Ly-Mee; McManus, Richard J

2017-02-13

Self-monitoring of hypertension is associated with lower systolic blood pressure (SBP). However, evidence for the use of self-monitoring to titrate antihypertensive medication by physicians is equivocal. Furthermore, there is some evidence for the efficacy of telemonitoring in the management of hypertension but it is not clear what this adds over and above self-monitoring. This trial aims to evaluate whether GP led antihypertensive titration using self-monitoring results in lower SBP compared to usual care and whether telemonitoring adds anything to self-monitoring alone. This will be a pragmatic primary care based, unblinded, randomised controlled trial of self-monitoring of BP with or without telemonitoring compared to usual care. Eligible patients will have poorly controlled hypertension (>140/90 mmHg) and will be recruited from primary care. Participants will be individually randomised to either usual care, self-monitoring alone, or self-monitoring with telemonitoring. The primary outcome of the trial will be difference in clinic SBP between intervention and control groups at 12 months adjusted for baseline SBP, gender, BP target and practice. At least 1110 patients will be sufficient to detect a difference in SBP between self-monitoring with or without telemonitoring and usual care of 5 mmHg with 90% power with an adjusted alpha of 0.017 (2-sided) to adjust for all three pairwise comparisons. Other outcomes will include adherence of anti-hypertensive medication, lifestyle behaviours, health-related quality of life, and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative sub study will gain insights into the views, experiences and decision making processes of patients and health care professionals focusing on the acceptability of self-monitoring and telemonitoring in the routine management of hypertension. The results of the trial will be directly applicable to primary care in the UK. If successful, self-monitoring of BP in people with hypertension would be applicable to hundreds of thousands of individuals in the UK. ISRCTN 83571366 . Registered 17 July 2014.

Refractory and Resistant Hypertension: Antihypertensive Treatment Failure versus Treatment Resistance

PubMed Central

2016-01-01

Resistant hypertension has for many decades been defined as difficult-to-treat hypertension in order to identify patients who may benefit from special diagnostic and/or therapeutic considerations. Recently, the term "refractory hypertension" has been proposed as a novel phenotype of antihypertensive failure, that is, patients whose blood pressure cannot be controlled with maximal treatment. Early studies of this phenotype indicate that it is uncommon, affecting less than 5% of patients with resistant hypertension. Risk factors for refractory hypertension include obesity, diabetes, chronic kidney disease, and especially, being of African origin. Patients with refractory are at high cardiovascular risk based on increased rates of known heart disease, prior stroke, and prior episodes of congestive heart failure. Mechanisms of refractory hypertension need exploration, but early studies suggest a possible role of heightened sympathetic tone as evidenced by increased office and ambulatory heart rates and higher urinary excretion of norepinephrine compared to patients with controlled resistant hypertension. Important negative findings argue against refractory hypertension being fluid dependent as is typical of resistant hypertension, including aldosterone levels, dietary sodium intake, and brain natriuretic peptide levels being similar or even less than patients with resistant hypertension and the failure to control blood pressure with use of intensive diuretic therapy, including both a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Further studies, especially longitudinal assessments, are needed to better characterize this extreme phenotype in terms of risk factors and outcomes and hopefully to identify effective treatment strategies. PMID:27721847

Unsuccessfully Treated Hypertension: A Major Public Health Problem With a Potential Solution.

PubMed

Furberg, Curt D; Sealey, Jean E; Blumenfeld, Jon D

2017-09-01

About one-half of all hypertensive adults do not have their blood pressure controlled. They are often prescribed medications that conform to national guidelines but they continue to have elevated blood pressure. This public health problem might be improved by applying plasma renin guided therapy. A contributor to the public health problem of unsuccessfully treated hypertension is that the circulating renin-angiotensin system (RAS) is not recognized in treatment guidelines as clinically relevant for the treatment of hypertension or as important as the body salt status for determining blood pressure levels. Another contributor to the problem is the lack of specificity in the package inserts for antihypertensive drugs. They do not specifically state under the heading "Indications" that RAS blockers are primarily most effective in hypertensive subjects with medium and high plasma renin levels; by contrast, natriuretic drugs are most effective in those with low plasma renin levels. Literature review. To address the problem of unsuccessfully treated hypertension, we recommend that the "Indications" section of package inserts for antihypertensive drugs be more specific. The primary indication for RAS blockers ought to be hypertension with medium and high plasma renin levels, and natriuretic agents for those with low plasma renin levels. Similar language ought to be added to treatment guidelines. Additionally, 3 other reasons for lack of blood pressure control also need to be addressed-failure to prescribe antihypertensive drugs to hypertensive subjects, failure of patients to fill prescriptions, and low drug adherence. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Are SGLT2 inhibitors reasonable antihypertensive drugs and renoprotective?

PubMed

Lovshin, J A; Gilbert, R E

2015-06-01

By eliminating glucose in the urine, the sodium-glucose-linked cotransporter-2 (SGLT2) inhibitors act as osmotic diuretics to lower blood pressure in addition to reducing plasma glucose and assisting with weight loss. While not approved as antihypertensive agents, the ability of this new class of antihyperglycemic agents to lower blood pressure is not insubstantial, and while not used primarily for this indication, they may assist diabetic individuals in attaining currently recommended blood pressure targets. In addition to lowering systemic pressure, preclinical and exploratory human studies suggest that SGLT2 inhibitors may also lower intraglomerular pressure, potentially reducing the rate of GFR decline in patients with diabetic nephropathy. However, given the lack of clinically meaningful endpoint data, the use of SGLT2 inhibitors, primarily, as either antihypertensive or renoprotective agents would, at present, be premature. Fortunately, further insight will be garnered from large, randomized controlled trials that will assess the effects of various SGLT2 inhibitors on cardiovascular and renal outcomes.

Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study.

PubMed

Rorie, David A; Rogers, Amy; Mackenzie, Isla S; Ford, Ian; Webb, David J; Willams, Bryan; Brown, Morris; Poulter, Neil; Findlay, Evelyn; Saywood, Wendy; MacDonald, Thomas M

2016-02-09

Nocturnal blood pressure (BP) appears to be a better predictor of cardiovascular outcome than daytime BP. The BP lowering effects of most antihypertensive therapies are often greater in the first 12 h compared to the next 12 h. The Treatment In Morning versus Evening (TIME) study aims to establish whether evening dosing is more cardioprotective than morning dosing. The TIME study uses the prospective, randomised, open-label, blinded end-point (PROBE) design. TIME recruits participants by advertising in the community, from primary and secondary care, and from databases of consented patients in the UK. Participants must be aged over 18 years, prescribed at least one antihypertensive drug taken once a day, and have a valid email address. After the participants have self-enrolled and consented on the secure TIME website (http://www.timestudy.co.uk) they are randomised to take their antihypertensive medication in the morning or the evening. Participant follow-ups are conducted after 1 month and then every 3 months by automated email. The trial is expected to run for 5 years, randomising 10,269 participants, with average participant follow-up being 4 years. The primary end point is hospitalisation for the composite end point of non-fatal myocardial infarction (MI), non-fatal stroke (cerebrovascular accident; CVA) or any vascular death determined by record-linkage. Secondary end points are: each component of the primary end point, hospitalisation for non-fatal stroke, hospitalisation for non-fatal MI, cardiovascular death, all-cause mortality, hospitalisation or death from congestive heart failure. The primary outcome will be a comparison of time to first event comparing morning versus evening dosing using an intention-to-treat analysis. The sample size is calculated for a two-sided test to detect 20% superiority at 80% power. TIME has ethical approval in the UK, and results will be published in a peer-reviewed journal. UKCRN17071; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Bayesian regression model for recurrent event data with event-varying covariate effects and event effect.

PubMed

Lin, Li-An; Luo, Sheng; Davis, Barry R

2018-01-01

In the course of hypertension, cardiovascular disease events (e.g., stroke, heart failure) occur frequently and recurrently. The scientific interest in such study may lie in the estimation of treatment effect while accounting for the correlation among event times. The correlation among recurrent event times come from two sources: subject-specific heterogeneity (e.g., varied lifestyles, genetic variations, and other unmeasurable effects) and event dependence (i.e., event incidences may change the risk of future recurrent events). Moreover, event incidences may change the disease progression so that there may exist event-varying covariate effects (the covariate effects may change after each event) and event effect (the effect of prior events on the future events). In this article, we propose a Bayesian regression model that not only accommodates correlation among recurrent events from both sources, but also explicitly characterizes the event-varying covariate effects and event effect. This model is especially useful in quantifying how the incidences of events change the effects of covariates and risk of future events. We compare the proposed model with several commonly used recurrent event models and apply our model to the motivating lipid-lowering trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (ALLHAT-LLT).

Bayesian regression model for recurrent event data with event-varying covariate effects and event effect

PubMed Central

Lin, Li-An; Luo, Sheng; Davis, Barry R.

2017-01-01

In the course of hypertension, cardiovascular disease events (e.g., stroke, heart failure) occur frequently and recurrently. The scientific interest in such study may lie in the estimation of treatment effect while accounting for the correlation among event times. The correlation among recurrent event times come from two sources: subject-specific heterogeneity (e.g., varied lifestyles, genetic variations, and other unmeasurable effects) and event dependence (i.e., event incidences may change the risk of future recurrent events). Moreover, event incidences may change the disease progression so that there may exist event-varying covariate effects (the covariate effects may change after each event) and event effect (the effect of prior events on the future events). In this article, we propose a Bayesian regression model that not only accommodates correlation among recurrent events from both sources, but also explicitly characterizes the event-varying covariate effects and event effect. This model is especially useful in quantifying how the incidences of events change the effects of covariates and risk of future events. We compare the proposed model with several commonly used recurrent event models and apply our model to the motivating lipid-lowering trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (ALLHAT-LLT). PMID:29755162

Angiotensin Receptor Blockades Effect on Peripheral Muscular and Central Aortic Arterial Stiffness: A Meta-Analysis of Randomized Controlled Trials and Systematic Review.

PubMed

Yen, Chih-Hsuan; Lai, Yau-Huei; Hung, Chung-Lieh; Lee, Ping-Ying; Kuo, Jen-Yuan; Yeh, Hung-I; Hou, Charles Jia-Yin; Chien, Kuo-Liong

2014-03-01

Previous clinical trials have demonstrated the impact of blocking upstream renin-angiotensin-axis with angiotensin converting enzyme inhibitors (ACEIs) on arterial stiffness as evaluated by pulse-wave velocity (PWV). We ran a meta-analysis to evaluate the anti-stiffness effect of powerful downstream angiotensin receptor blockades (ARBs) on peripheral and central arterial stiffness (brachial to ankle, ba-PWV; carotid to femoral, cf-PWV, respectively), using a systematic review to assess the clinical arterial stiffness issues. For our study, we searched the PubMed and Cochrane Library databases from inception to June 2013, targeting randomized controlled trials. ARBs along with other antihypertensive agents, ACEIs, calcium channel blockers (CCBs), beta-blockers and diuretics were evaluated to ascertain their comparable effect on ba-PWV and cf-PWV, respectively. A meta-analysis was conducted utilizing the fixed or random effect of the weighted mean change difference between the ARB and comparator groups, depending on the I(2) statistic heterogeneity measurement. In 2 trials treating patients with ARBs (n = 30), the ARBs insignificantly reduced levels of ba-PWV (pooled mean change difference -188, 95% CI -687, 311, p = 0.24 with significant heterogeneity) as compared to other hypertensive agents (ACEIs and CCBs, n = 77). Interestingly, ARBs (n = 20) had a superior capacity to reduce levels of ba-PWV than CCBs (n = 20) in single study results (mean change difference -400, 95% CI -477, -322, p < 0.05). In 7 trials which included a total of 653 patients, treatment with ARBs (n = 308) also insignificantly reduced cf-PWV (pool mean change difference -0.197, 95% CI -0.54, 0.14, p = 0.218) as compared to other anti-hypertensive agents. Our data suggested that ARBs had a similar effect as other anti-hypertensive agents in reducing ba-PWV and cf-PWV. Upon systematic review, the renin-angiotensin-axis system mechanism seems more significant than the direct vessel dilatation system in anti-arterial stiffness mechanism. Angiotension receptor blockage; Arterial stiffness; Meta-analysis; Systematic review.

Should African Americans have a lower blood pressure goal than other ethnic groups to prevent organ damage?

PubMed

Flack, John M; Okwuosa, Tochukwi; Sudhakar, Rajeev; Ference, Brian; Levy, Phillip

2012-12-01

African Americans manifest an inordinately high burden of hypertension, pressure-related target-organ injury (eg, left ventricular hypertrophy, stroke), and sub-optimal hypertension control rates to conventional levels (<140/90 mm Hg). A substantive proportion of the excessive premature mortality in African Americans relative to Whites is pressure-related. Randomized prospective pharmacologic hypertension end-point trials have shown invariable cardiovascular disease (CVD) risk reduction across a broad range of pre-treatment BP levels down to 110/70 mm Hg with the magnitude of CVD risk reduction across the 5 major antihypertensive drug classes being directly linked to degree of blood pressure (BP) lowering. Pooled endpoint data from pharmacologic hypertension trials in African Americans showed that CVD risk reduction was the same with major antihypertensive drug classes when similar levels of BP were achieved. A lower than conventional BP target for African Americans seems justified and prudent because attainment of lower BP should incrementally lower CVD risk in this high-risk population.

Pharmacokinetic evaluation and clinical utility of azilsartan medoxomil for the treatment of hypertension.

PubMed

Angeli, Fabio; Verdecchia, Paolo; Pascucci, Chiara; Poltronieri, Cristina; Reboldi, Gianpaolo

2013-03-01

Azilsartan medoxomil is a newly approved angiotensin-receptor blocker for the management of hypertension. It is a prodrug that is quickly hydrolyzed to the active moiety azilsartan, a potent and highly selective angiotensin-receptor blocker with estimated bioavailability of ∼ 60%. This new agent induces a potent and long-lasting antihypertensive effect. The effective therapeutic antihypertensive dosages of azilsartan medoxomil in humans vary from 40 to 80 mg/day. The authors review the results of clinical trials published in journals indexed in Medline, Scopus and Google Scholar. Primarily the authors discuss articles that analyze the safety and efficacy of azilsartan in lowering blood pressure. Clinical trials have demonstrated that azilsartan is superior to other angiotensin-receptor blockers in lowering blood pressure. However, the clinical blood pressure trials of azilsartan published to date have been mainly conducted in patients without serious comorbidities and it is not clear if azilsartan has advantages over other angiotensin-receptor blockers in the treatment of these types of hypertensive patients. In addition, it remains to be determined whether the specific pharmacologic and pharmacokinetic characteristics of azilsartan will have a clinically significant impact on long-term cardiovascular outcomes.

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

PubMed

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

2011-07-05

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

Advertising of antihypertensive medicines and prescription sales in Australia.

PubMed

Vitry, A; Lai, Y H

2009-11-01

Drug promotion is one of the main factors that influence prescribing practices, but there are limited data available to quantify the relationship between drug advertising and prescription sales. To investigate the relationship between advertising for antihypertensive medicines and prescription sales in Australia between 1993 and 2002. Retrospective observational study. Advertising trends were monitored by counting the number of advertisements published in three Australian medical journals. Monthly prescription dispensing data were obtained from Drug Utilisation Sub-Committee and expressed as numbers of defined daily doses/1000 inhabitants/day. Linear regression and cross-correlations of time series were used in the analysis. The drug classes the most heavily advertised, angiotensin-converting enzyme inhibitors and calcium channel blockers, were also the most prescribed during the study period, while the drugs the least advertised, thiazide diuretics and beta-blockers, were the least used. In 5 of the 7 main antihypertensive classes, the product the most advertised was also the most prescribed. Other factors, such as the publication of large clinical trials, may have also influenced prescribing patterns. Prescription sales of antihypertensives in Australia are correlated with promotional advertising. The newest and most expensive medicines may be chosen over older effective drugs by prescribers. New policies on drug promotion control need to be developed.

Section II: Reviews. Antihypertensive Drugs in Aircrew

DTIC Science & Technology

2001-06-01

Sleep 1997;20:806-11. utility in treating hypertensive emergencies. Only hydralazine and minoxidil are suitable for 7. Hampton JR. Comparative efficacy...like trials. European Heart J 1992;13(Suppl G):85- syndrome, the frequency of occurrence depending 91. on dose and duration. 4 Minoxidil causes severe

Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients

PubMed Central

2012-01-01

Background The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. Methods Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure <140/<90 mmHg during six months, the doses of bisoprolol and amlodipine should be increased to 10 mg/day with the possible addition of up to 2 g/day α-methyldopa. Results At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass index (28.2 kg/m2), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study. Conclusions NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible. PMID:22594907

Home blood pressure-guided antihypertensive therapy in chronic kidney disease: more data are needed.

PubMed

Georgianos, Panagiotis I; Champidou, Eleni; Liakopoulos, Vassilios; Balaskas, Elias V; Zebekakis, Pantelis E

2018-04-01

In the era of newly introduced hypertension guidelines recommending lower blood pressure (BP) targets for drug-treated hypertensives, the necessity for optimized management of hypertension becomes even more urgent. The concept of home BP-guided antihypertensive therapy is for long suggested as a simple and feasible approach to improve BP control rates and optimize the management of hypertension. Home BP-guided antihypertensive therapy is particularly applicable to hypertensives with chronic kidney disease (CKD) for several reasons including the following: (1) difficult-to-control BP and high BP variability in the CKD setting; (2) poor accuracy of office BP in determining hypertension control status and detecting "white-coat" and "masked" hypertension; (3) poor value of routine office BP recordings in predicting the longitudinal progression of target-organ damage; and (4) superiority of home BP over office BP recordings in prognosticating the risk of incident end-stage renal disease or death. The concept of home BP-guided antihypertensive therapy is even more relevant for those on hemodialysis, given the high intradialytic and interdialytic BP variability and poor value of conventional peridialytic BP recordings in estimating the actual BP load recorded outside of dialysis with the use of home or ambulatory BP monitoring. Randomized trials comparing home BP-guided antihypertensive therapy versus usual care are warranted to prove the feasibility and effectiveness of this therapeutic approach and convince clinicians for using home BP monitoring as the standard of care when managing hypertension, particularly in people with CKD or end-stage renal disease. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

Current Perspectives on Systemic Hypertension in Heart Failure with Preserved Ejection Fraction.

PubMed

Tam, Marty C; Lee, Ran; Cascino, Thomas M; Konerman, Matthew C; Hummel, Scott L

2017-02-01

Heart failure with preserved ejection fraction (HFpEF) is a prevalent but incompletely understood syndrome. Traditional models of HFpEF pathophysiology revolve around systemic HTN and other causes of increased left ventricular afterload leading to left ventricular hypertrophy (LVH) and diastolic dysfunction. However, emerging models attribute the development of HFpEF to systemic proinflammatory changes secondary to common comorbidities which include HTN. Alterations in passive ventricular stiffness, ventricular-arterial coupling, peripheral microvascular function, systolic reserve, and chronotropic response occur. As a result, HFpEF is heterogeneous in nature, making it difficult to prescribe uniform therapies to all patients. Nonetheless, treating systemic HTN remains a cornerstone of HFpEF management. Antihypertensive therapies have been linked to LVH regression and improvement in diastolic dysfunction. However, to date, no therapies have definitive mortality benefit in HFpEF. Non-pharmacologic management for HTN, including dietary modification, exercise, and treating sleep disordered breathing, may provide some morbidity benefit in the HFpEF population. Future research is need to identify effective treatments, perhaps in more specific subgroups, and focus may need to shift from reducing mortality to improving exercise capacity and symptoms. Tailoring antihypertensive therapies to specific phenotypes of HFpEF may be an important component of this strategy.

Thiazide diuretics in the treatment of hypertension: an update.

PubMed

Salvetti, Antonio; Ghiadoni, Lorenzo

2006-04-01

Thiazide diuretics were the first tolerated efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in placebo-controlled clinical studies. Although these drugs today still are considered a fundamental therapeutic tool for the treatment of hypertensive patients, the following considerations should be taken into account. Although there are some indications that chlorthalidone can offer additional advantages as compared with other compounds, a recent meta-analysis of placebo-controlled trials suggested that the beneficial effects of thiazide diuretics could be a class effect. Thiazide diuretics must be used at appropriate and/or optimal doses to achieve the optimal antihypertensive effect with the smallest occurrence of side effects, including alterations in glucose and lipid profiles and hypokalemia. Moreover, because thiazide diuretics can increase the incidence of new-onset diabetes, especially when combined with beta blockers, caution is advised in using these drugs above all in patients who are at high risk for developing diabetes, in whom thiazide diuretics should be used at the lowest active dose and possibly in combination with drugs that block the renin-angiotensin system. Finally, the current debate on whether thiazide diuretics are the first-choice drug for most patients with uncomplicated hypertension, as stated in the Seventh Joint National Committee Report, or are included in the major classes of antihypertensive agents that are suitable for initiation and maintenance of therapy, as reported in the European Society of Hypertension-European Society of Cardiology Guidelines, derives from different interpretations of controlled clinical trial data on drug class comparison and of cost-benefit analyses. However, considering that the benefit of antihypertensive drugs seems to be due principally to BP lowering per se without definitive evidence of the superiority of a particular drug class and that there is no cost-benefit analysis showing the superiority of thiazide diuretics, it is believed that these drugs should not be considered as the only first-choice drug but included among first-choice drugs.

Effectiveness of malic acid 1% in patients with xerostomia induced by antihypertensive drugs

PubMed Central

Guardia, Javier; Aguilar-Salvatierra, Antonio; Cabrera-Ayala, Maribel; Maté-Sánchez de-Val, José E.; Calvo-Guirado, José L.

2013-01-01

Objectives: Assessing the clinical effectiveness of a topical sialogogue on spray (malic acid, 1%) in the treatment of xerostomia induced by antihypertensive drugs. Study Design: This research has been carried out through a randomized double-blind clinical trial. 45 patients suffering from hypertensive drugs-induced xerostomia were divided into 2 groups: the first group (25 patients) received a topical sialogogue on spray (malic acid, 1%) whereas the second group (20 patients) received a placebo. Both of them were administered on demand for 2 weeks. Dry Mouth Questionnaire (DMQ) was used in order to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after application, were measured. All the statistical analyses were performed by using SPSS software v17.0. Different DMQ scores at the earliest and final stage of the trial were analysed by using Mann-Whitney U test, whereas Student’s T-test was used to analyse salivary flows. Critical p-value was established at p<0.05. Results: DMQ scores increased significantly (clinical recovery) from 1.21 to 3.36 points (p<0.05) after malic acid (1%) application whereas DMQ scores increased from 1.18 to 1.34 points (p>0.05) after placebo application. After two weeks of treatment with malic acid, unstimulated salivary flow increased from 0.17 to 0.242 mL/min whereas the stimulated one increased from 0.66 to 0.92 mL/min (p<0.05). After placebo application unstimulated flow ranged from 0.152 to 0.146 mL/min and stimulated flow increased from 0.67 to 0.70 mL/min (p>0.05). Conclusions: Malic acid 1% spray improved antihypertensive-induced xerostomia and stimulated the production of saliva. Key words:Xerostomia, hyposialia, malic acid, antihypertensive drugs. PMID:22926481

Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis.

PubMed

Sundström, Johan; Arima, Hisatomi; Jackson, Rod; Turnbull, Fiona; Rahimi, Kazem; Chalmers, John; Woodward, Mark; Neal, Bruce

2015-02-03

Effects of blood pressure reduction in persons with grade 1 hypertension are unclear. To investigate whether pharmacologic blood pressure reduction prevents cardiovascular events and deaths in persons with grade 1 hypertension. Trials included in the BPLTTC (Blood Pressure Lowering Treatment Trialists' Collaboration) and trials identified from a previous review and electronic database searches. Patients without cardiovascular disease with blood pressures in the grade 1 hypertension range (140 to 159/90 to 99 mm Hg) who were randomly assigned to an active (antihypertensive drug or more intensive regimen) or control (placebo or less intensive regimen) blood pressure-lowering regimen. Individual-patient data from BPLTTC trials and aggregate data from other trials were extracted. Risk of bias was assessed for all trials. Individual-patient data involved 10 comparisons from trials where most patients had diabetes, and aggregate data involved 3 comparisons from trials of patients without diabetes. The average blood pressure reduction was about 3.6/2.4 mm Hg. Over 5 years, odds ratios were 0.86 (95% CI, 0.74 to 1.01) for total cardiovascular events, 0.72 (CI, 0.55 to 0.94) for strokes, 0.91 (CI, 0.74 to 1.12) for coronary events, 0.80 (CI, 0.57 to 1.12) for heart failure, 0.75 (CI, 0.57 to 0.98) for cardiovascular deaths, and 0.78 (CI, 0.67 to 0.92) for total deaths. Results were similar in secondary analyses. Withdrawal from treatment due to adverse effects was more common in the active groups. Blood pressure reductions and numbers of events were small. Blood pressure-lowering therapy is likely to prevent stroke and death in patients with uncomplicated grade 1 hypertension. Swedish Heart-Lung Foundation, Swedish Research Council, Australian Research Council, and National Health and Medical Research Council of Australia.

Comparison between valsartan and amlodipine regarding cardiovascular morbidity and mortality in hypertensive patients with glucose intolerance: NAGOYA HEART Study.

PubMed

Muramatsu, Takashi; Matsushita, Kunihiro; Yamashita, Kentaro; Kondo, Takahisa; Maeda, Kengo; Shintani, Satoshi; Ichimiya, Satoshi; Ohno, Miyoshi; Sone, Takahito; Ikeda, Nobuo; Watarai, Masato; Murohara, Toyoaki

2012-03-01

It has not been fully examined whether angiotensin II receptor blocker is superior to calcium channel blocker to reduce cardiovascular events in hypertensive patients with glucose intolerance. A prospective, open-labeled, randomized, controlled trial was conducted for Japanese hypertensive patients with type 2 diabetes mellitus or impaired glucose tolerance. A total of 1150 patients (women: 34%; mean age: 63 years; diabetes mellitus: 82%) were randomly assigned to receive either valsartan- or amlodipine-based antihypertensive treatment. Primary outcome was a composite of acute myocardial infarction, stroke, coronary revascularization, admission attributed to heart failure, or sudden cardiac death. Blood pressure was 145/82 and 144/81 mm Hg, and glycosylated hemoglobin was 7.0% and 6.9% at baseline in the valsartan group and the amlodipine group, respectively. Both of them were equally controlled between the 2 groups during the study. The median follow-up period was 3.2 years, and primary outcome had occurred in 54 patients in the valsartan group and 56 in the amlodipine group (hazard ratio: 0.97 [95% CI: 0.66-1.40]; P=0.85). Patients in the valsartan group had a significantly lower incidence of heart failure than in the amlodipine group (hazard ratio: 0.20 [95% CI: 0.06-0.69]; P=0.01). Other components and all-cause mortality were not significantly different between the 2 groups. Composite cardiovascular outcomes were comparable between the valsartan- and amlodipine-based treatments in Japanese hypertensive patients with glucose intolerance. Admission because of heart failure was significantly less in the valsartan group.

Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

PubMed

Reboussin, David M; Allen, Norrina B; Griswold, Michael E; Guallar, Eliseo; Hong, Yuling; Lackland, Daniel T; Miller, Edgar Pete R; Polonsky, Tamar; Thompson-Paul, Angela M; Vupputuri, Suma

2018-05-15

To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of <130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (i.e., angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome. Copyright © 2018 American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.

The value of irbesartan in the management of hypertension.

PubMed

Bramlage, Peter; Durand-Zaleski, Isabelle; Desai, Nisha; Pirk, Olaf; Hacker, Caroline

2009-08-01

Elevated blood pressure levels are highly prevalent and are a major reason for cardiovascular events and thus place a significant financial burden on healthcare systems worldwide. Guidelines recommend five first-line anti-hypertensive drug classes, but compelling indications may indicate favoring one drug class over another. Angiotensin receptor blockers (ARBs) have demonstrated a blood pressure lowering efficacy which is at least comparable with other drug classes, including ACE inhibitors (ACE-I), beta-blockers, calcium channel blockers and diuretics. They have, in addition, a lower side effect profile than other drug classes and patients on ARBs are more persistent with therapy. Compelling indications for the use of ARBs are heart failure, post-myocardial infarction, diabetic nephropathy, proteinuria/microalbuminuria, left ventricular hypertrophy, atrial fibrillation, metabolic syndrome and ACE-I induced cough. The ARB irbesartan has demonstrated a high efficacy in lowering blood pressure, which has been shown to be at least comparable with ACE-Is and superior to other ARBs such as losartan and valsartan. This translated into a better cost-effectiveness for irbesartan than for valsartan and losartan in the treatment of hypertension. In addition, irbesartan has been shown to be effective in both early and late stage diabetic nephropathy. It has further demonstrated considerable cost savings over standard therapy including beta-blockers, diuretics and non-dihydropyridine calcium channel blockers at all stages of kidney disease. Based on efficacy data from the Irbesartan Diabetic Nephropathy Trial and Reduction of Endpoints in NIDDM (non insulin dependant diabetes melitis) with the Angiotensin II Antagonist Losartan Study, it has also demonstrated cost savings over losartan in late stage renal disease. While both losartan and irbesartan are registered for the treatment of late stage diabetic nephropathy, irbesartan is also registered for early stage diabetic nephropathy in the EU. In summary, the data from randomized clinical trials on the efficacy of antihypertensive drugs provides an indication of their real value to patients. In addition observational data from clinical practice and proven end-organ protection in diabetic nephropathy provides further evidence of the true value of irbesartan compared to other ARBs in the treatment of hypertension.

First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension.

PubMed

Xue, Hao; Lu, Zhuang; Tang, Wen Lu; Pang, Lu Wei; Wang, Gan Mi; Wong, Gavin W K; Wright, James M

2015-01-11

Renin-angiotensin system (RAS) inhibitors are widely prescribed for treatment of hypertension, especially for diabetic patients on the basis of postulated advantages for the reduction of diabetic nephropathy and cardiovascular morbidity and mortality. Despite widespread use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for hypertension in both diabetic and non-diabetic patients, the efficacy and safety of RAS inhibitors compared to other antihypertensive drug classes remains unclear. To evaluate the benefits and harms of first-line RAS inhibitors compared to other first-line antihypertensive drugs in patients with hypertension. We searched the Cochrane Hypertension Group's Specialised Register, MEDLINE, MEDLINE In-Process, EMBASE and ClinicalTrials.gov for randomized controlled trials up to November 19, 2014 and the Cochrane Central Register of Controlled Trials (CENTRAL) up to October 19, 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Cochrane Hypertension Group's Specialised Register. We included randomized, active-controlled, double-blinded studies with at least six months follow-up in people with primary elevated blood pressure (≥130/85 mmHg), which compared first-line RAS inhibitors with other first-line antihypertensive drug classes and reported morbidity and mortality or blood pressure outcomes. Patients with proven secondary hypertension were excluded. Two authors independently selected the included trials, evaluated the risk of bias and entered the data for analysis. We included 42 studies, involving 65,733 participants, with a mean age of 66 years. Much of the evidence for our key outcomes is dominated by a small number of large studies at a low risk of bias for most sources of bias. Imbalances in the added second-line antihypertensive drugs in some of the studies were important enough for us to downgrade the quality of the evidence.Primary outcomes were all-cause death, fatal and non-fatal stroke, fatal and non-fatal myocardial infarction (MI), fatal and non-fatal congestive heart failure (CHF) requiring hospitalization, total cardiovascular (CV) events (consisted of fatal and non-fatal stroke, fatal and non-fatal MI and fatal and non-fatal CHF requiring hospitalizations), and ESRF. Secondary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR).Compared with first-line calcium channel blockers (CCBs), we found moderate quality evidence that first-line RAS inhibitors decreased heart failure (HF) (35,143 participants in 5 RCTs, RR 0.83, 95% CI 0.77 to 0.90, ARR 1.2%), and moderate quality evidence that they increased stroke (34,673 participants in 4 RCTs, RR 1.19, 95% CI 1.08 to 1.32, ARI 0.7%). They had similar effects on all-cause death (35,226 participants in 5 RCTs, RR 1.03, 95% CI 0.98 to 1.09; moderate quality evidence), total CV events (35,223 participants in 6 RCTs, RR 0.98, 95% CI 0.93 to 1.02; moderate quality evidence), total MI (35,043 participants in 5 RCTs, RR 1.01, 95% CI 0.93 to 1.09; moderate quality evidence). The results for ESRF do not exclude potentially important differences (19,551 participants in 4 RCTs, RR 0.88, 95% CI 0.74 to 1.05; low quality evidence).Compared with first-line thiazides, we found moderate quality evidence that first-line RAS inhibitors increased HF (24,309 participants in 1 RCT, RR 1.19, 95% CI 1.07 to 1.31, ARI 1.0%), and increased stroke (24,309 participants in 1 RCT, RR 1.14, 95% CI 1.02 to 1.28, ARI 0.6%). They had similar effects on all-cause death (24,309 participants in 1 RCT, RR 1.00, 95% CI 0.94 to 1.07; moderate quality evidence), total CV events (24,379 participants in 2 RCTs, RR 1.05, 95% CI 1.00 to 1.11; moderate quality evidence), and total MI (24,379 participants in 2 RCTs, RR 0.93, 95% CI 0.86 to 1.01; moderate quality evidence). Results for ESRF do not exclude potentially important differences (24,309 participants in 1 RCT, RR 1.10, 95% CI 0.88 to 1.37; low quality evidence).Compared with first-line beta-blockers, we found low quality evidence that first-line RAS inhibitors decreased total CV events (9239 participants in 2 RCTs, RR 0.88, 95% CI 0.80 to 0.98, ARR 1.7%), and low quality evidence that they decreased stroke (9193 participants in 1 RCT, RR 0.75, 95% CI 0.63 to 0.88, ARR 1.7% ). Our analyses do not exclude potentially important differences between first-line RAS inhibitors and beta-blockers on all-cause death (9193 participants in 1 RCT, RR 0.89, 95% CI 0.78 to 1.01; low quality evidence), HF (9193 participants in 1 RCT, RR 0.95, 95% CI 0.76 to 1.18; low quality evidence), and total MI (9239 participants in 2 RCTs, RR 1.05, 95% CI 0.86 to 1.27; low quality evidence).Blood pressure comparisons between RAS inhibitors and other classes showed either no differences or small differences that did not necessarily correlate with the differences in the morbidity outcomes.In the protocol, we identified non-fatal serious adverse events (SAE) as a primary outcome. However, when we extracted the data from included studies, none of them reported total SAE in a manner that could be used in the review. Therefore, there is no information about SAE in the review. We found predominantly moderate quality evidence that all-cause mortality is similar when first-line RAS inhibitors are compared to other first-line antihypertensive agents. First-line thiazides caused less HF and stroke than first-line RAS inhibitors. The quality of the evidence comparing first-line beta-blockers and first-line RAS inhibitors was low and the lower risk of total CV events and stroke seen with RAS inhibitors may change with the publication of additional trials. Compared with first-line CCBs, first-line RAS inhibitors reduced HF but increased stroke. The magnitude of the reduction in HF exceeded the increase in stroke. The small differences in effect on blood pressure between the different classes of drugs did not correlate with the differences in the primary outcomes.

Persistence with treatment for hypertension in actual practice

PubMed Central

Caro, J J; Salas, M; Speckman, J L; Raggio, G; Jackson, J D

1999-01-01

BACKGROUND: Despite the existence of efficacious medications, many patients in actual practice remain with uncontrolled hypertension. Randomized clinical trials, cannot address this issue well given their highly restricted environment. This paper examines persistence with antihypertensive therapy among patients in actual practice. METHODS: Cohort study of patients who received a diagnosis of hypertension and were treated between 1989 and 1994 identified through the Saskatchewan Health databases. Patients with concurrent diagnoses likely to affect initial treatment choice were excluded. The resulting population of 79,591 subjects was grouped into those with established hypertension (52,227 [66%]) and those with newly diagnosed hypertension (27,364 [34%]). The initial antihypertensive prescription, subsequent changes in treatment and persistence with antihypertensive therapy were analysed. RESULTS: Persistence with antihypertensive therapy decreased in the first 6 months after treatment was started and continued to decline over the next 4 years. Of the patients with newly diagnosed hypertension, only 78% persisted with therapy at the end of 1 year, as compared with 97% of the patients with established hypertension (p < 0.001). Among those with newly diagnosed hypertension, older patients were more likely than younger ones to persist, and women were more likely than men to persist (p < 0.001). INTERPRETATION: This analysis of actual practice data indicates that barriers to persistence occur early in the therapeutic course and that achieving successful therapy when treatment is started is important to maintaining long-term persistence. PMID:9934341

Alpha1-adrenergic blockers: current usage considerations.

PubMed

Sica, Domenic A

2005-12-01

Alpha1-adrenergic-blocking drugs are effective in reducing blood pressure and do so in a fashion comparable to most other antihypertensive drug classes. These compounds are most effective in patients in the upright position, reducing systolic and diastolic pressures by 8%-10%. Alpha1-adrenergic-blocking drugs incrementally reduce blood pressure when combined with most drug classes and are the only antihypertensive drug class to improve plasma lipid profiles. Alpha1-adrenergic-blocking drugs are also accepted as important elements of the treatment plan for symptomatic benign prostatic hypertrophy. Dose escalation of an alpha1-adrenergic-blocking drug can trigger renal Na+ retention, and the ensuing volume expansion can attenuate its blood pressure-lowering effect. Orthostatic hypotension can occur with these compounds, particularly when a patient is volume-contracted. Dizziness, headache, and drowsiness are common side effects with alpha1-adrenergic blockers. A modest decline in the use of doxazosin and other alpha1-adrenergic-blocking drugs has occurred coincident to the early termination of the doxazosin treatment arm in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

2015 Oman Heart Association guidelines for the management of hypertension : practical recommendations from the Oman Heart Association (OHA).

PubMed

El-Deeb, Mohammed H; Sulaiman, Kadhim J; Al-Riyami, Abdullah A; Mohsin, Nabil; Al-Mukhaini, Mohamed; Al-Lamki, Mohamed; Al-Busaidi, Noor; Al-Salmi, Issa; Al-Lawati, Jawad; Al-Rawahi, Najib; Al-Riyami, Mohamed B; Abdul-Rahman, Said; Al-Hinai, Said; Jaffer, Batool; Al-Wahaebi, Ahmed; Al-Khalili, Hanan; Al-Zadjali, Matllooba

2015-03-01

Hypertension (HTN) is a major independent risk factor for the development of stroke, coronary artery disease (CAD), peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD). HTN is a growing public health problem in Oman, almost certainly the most prevalent modifiable risk factor for cardiovascular disease (CVD). The risk of CVD in patients with HTN can be greatly reduced with lifestyle modifications and effective antihypertensive therapy. Randomized trials have shown that blood pressure (BP) lowering produces rapid reductions in CV risk. Several studies have shown that the majority of the hypertensive patients remain uncontrolled. It is well established that the observed poor control of the disease is not only related to poor adherence to medications, but also to limited awareness and adherence to evidence-based management of hypertension among physicians. Several guidelines for the management of patients with hypertension have been published. However, the aim of this document is to provide the busy physicians in Oman with more concise and direct approach towards implementing these guidelines into clinical practice.

Recruitment Strategies and Costs Associated With Enrolling People With Insomnia and High Blood Pressure Into an Online Behavioral Sleep Intervention: A Single-Site Pilot Study.

PubMed

Routledge, Faye S; Davis, Tara D; Dunbar, Sandra B

Recruitment in clinical research is a common challenge and source of study failure. The reporting of recruitment methods and costs in hypertension trials is limited especially for smaller, single-site trials, online intervention trials, and trials using newer online recruitment strategies. The aims of this study are to describe and examine the feasibility of newer online-e-mail recruitment strategies and traditional recruitment strategies used to enroll participants with insomnia and high blood pressure into an online behavioral sleep intervention study (Sleeping for Heart Health). The 16 online-e-mail-based and traditional recruitment strategies used are described. Recruitment strategy feasibility was examined by study interest and enrollee yields, conversion rates, and costs (direct, remuneration, labor, and cost per enrollee). From August 2014 to October 2015, 183 people were screened and 58 (31.7%) enrolled in the study (51.1 ± 12.9 years, 63.8% female, 72.4% African American, 136 ± 12/88 ± 7 mm Hg, 87.9% self-reported hypertension, 67.2% self-reported antihypertensive medication use). The recruitment strategies yielding the highest enrollees were the university hospital phone waiting message system (25.4%), Craigslist (22.4%), and flyers (20.3%) at a per enrollee cost of $42.84, $98.90, and $128.27, respectively. The university hospital phone waiting message system (55.6%) and flyers (54.5%) had the highest interested participant to enrolled participant conversion rate of all recruitment strategies. Approximately 70% of all enrolled participants were recruited from the university hospital phone waiting message system, Craigslist, or flyers. Given the recruitment challenges that most researchers face, we encourage the documenting, assessing, and reporting of detailed recruitment strategies and associated recruitment costs so that other researchers may benefit.

An open-label, multicenter, flexible dose study to evaluate the efficacy and safety of Viagra (sildenafil citrate) in Korean men with erectile dysfunction and arterial hypertension who are taking antihypertensive agents.

PubMed

Park, Hyun Jun; Park, Nam Cheol; Shim, Hong Bang; Park, Jong Kwan; Lee, Sung Won; Park, Kwangsung; Kim, Sae Woong; Moon, Ki Hak; Lee, Dong Hyeon; Yoon, Sang Jin

2008-10-01

Erectile dysfunction (ED) is common among men taking antihypertensive agents to control blood pressure. We evaluated the efficacy and safety of sildenafil citrate in men with ED taking antihypertensive agents. A total of 198 male subjects, aged 20 years and older were enrolled. This study was conducted for 10 weeks as an open-label, multicenter and flexible dose trial with a 2-week screening period and an 8-week treatment phase. Subjects were asked to complete Event Log Worksheets, as well as the International Index of Erectile Function (IIEF) and the Global Efficacy Assessment Questions (GEAQ) questionnaires during the study period. The average age among the 167 subjects who completed the study was 55.8 (31.7 to 77.1). The scores for questions 3 and 4 of IIEF improved from 2.3 and 1.8 at baseline to 3.7 and 3.4 at week 4 and 3.8 and 3.4 at week 8, respectively. There were 86.3% of the patients reported improved erectile function at week 8; 88.3% of the patients reported improved ability to achieve sexual intercourse at week 8. There were no significant differences observed in the responses to questions 3 and 4 of IIEF and GEAQ by the number of antihypertensive agents taken. The adverse events were facial flushing (20.1%), headache (11.7%), palpitation (5.0%), rhinitis (2.8%), URI (2.8%), dizziness (2.2%), dyspnea (2.2%), and nausea (1.7%). Sildenafil citrate is an effective treatment for ED; it is safe and well tolerated by patients with ED taking multiple antihypertensive agents for arterial hypertension.

Hibiscus sabdariffa L. tea (tisane) lowers blood pressure in prehypertensive and mildly hypertensive adults: a randomized, placebo-controlled clinical trial

USDA-ARS?s Scientific Manuscript database

Background: In vitro studies have shown Hibiscus sabdariffa L., an ingredient found in many herbal tea blends and other beverages, has antioxidant properties, and, in animal models, extracts of its calyces have demonstrated hypocholesterolemic and anti-hypertensive properties. Objective: To exa...

75 FR 70273 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... Institute Special Emphasis Panel, The Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial... Research Demonstration and Dissemination Projects. Date: December 14, 2010. Time: 8 a.m. to 2 p.m. Agenda... Assistance Program Nos. 93.233, National Center for Sleep Disorders Research; 93.837, Heart and Vascular...

Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial

PubMed Central

2012-01-01

Background Hawthorn extract has been used for cardiovascular diseases for centuries. Recent trials have demonstrated its efficacy for the treatment of heart failure, and the results of several small trials suggest it may lower blood pressure. However, there is little published evidence to guide its dosing. The blood pressure lowering effect of hawthorn has been linked to nitric oxide-mediated vasodilation. The aim of this study was to investigate the relationship between hawthorn extract dose and brachial artery flow mediated dilation (FMD), an indirect measure of nitric oxide release. Methods We used a four-period cross-over design to evaluate brachial artery FMD in response to placebo or hawthorn extract (standardized to 50 mg oligomeric procyanidin per 250 mg extract). Randomly sequenced doses of hawthorn extract (1000 mg, 1500 mg, and 2500 mg) and placebo were assigned to each participant. Doses were taken twice daily for 3 1/2 days followed by FMD and a 4-day washout before proceeding to the next dosing period. Results Twenty-one prehypertensive or mildly hypertensive adults completed the study. There was no evidence of a dose-response effect for our main outcome (FMD percent) or any of our secondary outcomes (absolute change in brachial artery diameter and blood pressure). Most participants indicated that if given evidence that hawthorn could lower their blood pressure, they would be likely to use it either in conjunction with or instead of lifestyle modification or anti-hypertensive medications. Conclusion We found no evidence of a dose-response effect of hawthorn extract on FMD. If hawthorn has a blood pressure lowering effect, it is likely to be mediated via an NO-independent mechanism. Trial Registration This trial has been registered with ClinicalTrials.gov, a service of the U.S. National Institutes of Health: NCT01331486. PMID:22458601

Rate of Change in Renal Function and Mortality in Elderly Treated Hypertensive Patients

PubMed Central

Langham, Robyn G.; Ademi, Zanfina; Owen, Alice; Krum, Henry; Wing, Lindon M.H.; Nelson, Mark R.; Reid, Christopher M.

2015-01-01

Background and objectives Evidence relating the rate of change in renal function, measured as eGFR, after antihypertensive treatment in elderly patients to clinical outcome is sparse. This study characterized the rate of change in eGFR after commencement of antihypertensive treatment in an elderly population, the factors associated with eGFR rate change, and the rate’s association with all-cause and cardiovascular mortality. Design, setting, participants, & measurements Data from the Second Australian National Blood Pressure study were used, where 6083 hypertensive participants aged ≥65 years were enrolled during 1995–1997 and followed for a median of 4.1 years (in-trial). Following the Second Australian National Blood Pressure study, participants were followed-up for a further median 6.9 years (post-trial). The annual rate of change in the eGFR was calculated in 4940 participants using creatinine measurements during the in-trial period and classified into quintiles (Q) on the basis of the following eGFR changes: rapid decline (Q1), decline (Q2), stable (Q3), increase (Q4), and rapid increase (Q5). Results A rapid decline in eGFR in comparison with those with stable eGFRs during the in-trial period was associated with older age, living in a rural area, wider pulse pressure at baseline, receiving diuretic-based therapy, taking multiple antihypertensive drugs, and having blood pressure <140/90 mmHg during the study. However, a rapid increase in eGFR was observed in younger women and those with a higher cholesterol level. After adjustment for baseline and in-trial covariates, Cox-proportional hazard models showed a significantly greater risk for both all-cause (hazard ratio, 1.28; 95% confidence interval, 1.09 to 1.52; P=0.003) and cardiovascular (hazard ratio, 1.40; 95% confidence interval, 1.11 to 1.76; P=0.004) mortality in the rapid decline group compared with the stable group over a median of 7.2 years after the last eGFR measure. No significant association with mortality was observed for a rapid increase in eGFR. Conclusions In elderly persons with treated hypertension, a rapid decline in eGFR is associated with a higher risk of mortality. PMID:25901093

Rate of change in renal function and mortality in elderly treated hypertensive patients.

PubMed

Chowdhury, Enayet K; Langham, Robyn G; Ademi, Zanfina; Owen, Alice; Krum, Henry; Wing, Lindon M H; Nelson, Mark R; Reid, Christopher M

2015-07-07

Evidence relating the rate of change in renal function, measured as eGFR, after antihypertensive treatment in elderly patients to clinical outcome is sparse. This study characterized the rate of change in eGFR after commencement of antihypertensive treatment in an elderly population, the factors associated with eGFR rate change, and the rate's association with all-cause and cardiovascular mortality. Data from the Second Australian National Blood Pressure study were used, where 6083 hypertensive participants aged ≥65 years were enrolled during 1995-1997 and followed for a median of 4.1 years (in-trial). Following the Second Australian National Blood Pressure study, participants were followed-up for a further median 6.9 years (post-trial). The annual rate of change in the eGFR was calculated in 4940 participants using creatinine measurements during the in-trial period and classified into quintiles (Q) on the basis of the following eGFR changes: rapid decline (Q1), decline (Q2), stable (Q3), increase (Q4), and rapid increase (Q5). A rapid decline in eGFR in comparison with those with stable eGFRs during the in-trial period was associated with older age, living in a rural area, wider pulse pressure at baseline, receiving diuretic-based therapy, taking multiple antihypertensive drugs, and having blood pressure <140/90 mmHg during the study. However, a rapid increase in eGFR was observed in younger women and those with a higher cholesterol level. After adjustment for baseline and in-trial covariates, Cox-proportional hazard models showed a significantly greater risk for both all-cause (hazard ratio, 1.28; 95% confidence interval, 1.09 to 1.52; P=0.003) and cardiovascular (hazard ratio, 1.40; 95% confidence interval, 1.11 to 1.76; P=0.004) mortality in the rapid decline group compared with the stable group over a median of 7.2 years after the last eGFR measure. No significant association with mortality was observed for a rapid increase in eGFR. In elderly persons with treated hypertension, a rapid decline in eGFR is associated with a higher risk of mortality. Copyright © 2015 by the American Society of Nephrology.

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

PubMed

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

2017-09-15

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

Hypertension Treatment and Concern About Falling: Baseline Data from the Systolic Blood Pressure Intervention Trial.

PubMed

Berlowitz, Dan R; Breaux-Shropshire, Tonya; Foy, Capri G; Gren, Lisa H; Kazis, Lewis; Lerner, Alan J; Newman, Jill C; Powell, James R; Riley, William T; Rosman, Robert; Wadley, Virginia G; Williams, Julie A

2016-11-01

To determine the extent of concern about falling in older adults with hypertension, whether lower blood pressure (BP) and greater use of antihypertensive medications are associated with greater concern about falling, and whether lower BP has a greater effect on concern about falling in older and more functionally impaired individuals. Secondary analysis involving cross-sectional study of baseline characteristics of participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). Approximately 100 outpatient sites. SPRINT enrollees aged 50 and older (mean age 69) diagnosed with hypertension (N = 2,299). Concern about falling was determined using the shortened version of the Falls Efficacy Scale International as measured at the baseline examination. Mild concern about falling was present in 29.3% of participants and moderate to severe concern in 17.9%. Neither low BP (systolic BP<120 mmHg, diastolic BP <70 mmHg) nor orthostatic hypotension was associated with concern about falling (P > .10). Participants with moderate to severe concern about falling were taking significantly more antihypertensive medications than those with mild or no concern. After adjusting for baseline characteristics, no associations were evident between BP, medications, and concern about falling. Results were similar in older and younger participants; interactions between BP and age and functional status were not significantly associated with concern about falling. Although concern about falling is common in older adults with hypertension, it was not found to be associated with low BP or use of more antihypertensive medications in baseline data from SPRINT. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Improving hypertension management through pharmacist prescribing; the rural alberta clinical trial in optimizing hypertension (Rural RxACTION): trial design and methods

PubMed Central

2011-01-01

Background Patients with hypertension continue to have less than optimal blood pressure control, with nearly one in five Canadian adults having hypertension. Pharmacist prescribing is gaining favor as a potential clinically efficacious and cost-effective means to improve both access and quality of care. With Alberta being the first province in Canada to have independent prescribing by pharmacists, it offers a unique opportunity to evaluate outcomes in patients who are prescribed antihypertensive therapy by pharmacists. Methods The study is a randomized controlled trial of enhanced pharmacist care, with the unit of randomization being the patient. Participants will be randomized to enhanced pharmacist care (patient identification, assessment, education, close follow-up, and prescribing/titration of antihypertensive medications) or usual care. Participants are patients in rural Alberta with undiagnosed/uncontrolled blood pressure, as defined by the Canadian Hypertension Education Program. The primary outcome is the change in systolic blood pressure between baseline and 24 weeks in the enhanced-care versus usual-care arms. There are also three substudies running in conjunction with the project examining different remuneration models, investigating patient knowledge, and assessing health-resource utilization amongst patients in each group. Discussion To date, one-third of the required sample size has been recruited. There are 15 communities and 17 pharmacists actively screening, recruiting, and following patients. This study will provide high-level evidence regarding pharmacist prescribing. Trial Registration Clinicaltrials.gov NCT00878566. PMID:21834970

Long-term treatment of severe hypertension with minoxidil.

PubMed Central

Nawar, T.; Nolin, L.; Plante, G. E.; Caron, C.; Montambault, P.

1977-01-01

Minoxidil, a new potent hypotensive agent, was used as the primary antihypertensive agent in 11 patients--10 men and 1 woman aged 35 to 54 years with severe hypertension that was refractory to treatment with maximal (or maximally tolerated) doses of conventional antihypertensive agents. Six patients had severely impaired renal function and three of them were undergoing long-term hemodialysis. The patients were given 2.5 to 40 mg/d of minoxidil for periods of 2 to 29 months. All except one who was almost anuric received propranolol and diuretics. Blood pressure was controlled satisfactorily in all patients. In two patients the hypertension became partially resistant after 1 year of treatment. The main side effects were sodium retention, tachycardia and hirsutism. Renal function remained stable or improved and hemodialysis was discontinued in two patients. Minoxidil is a remarkably potent hypotensive with relatively few side effects and seems particularly advantageous in patients with chronic renal failure. PMID:603847

Massive Bilateral Serous Retinal Detachment in a Case of Hypertensive Chorioretinopathy

PubMed Central

Villalba-Pinto, Luis; Hernández-Ortega, M. Ángeles; de los Mozos, F. Javier Lavid; Pascual-Camps, Isabel; Dolz-Marco, Rosa; Arevalo, J. Fernando; Gallego-Pinazo, Roberto

2014-01-01

Introduction Systemic high blood pressure is related to a variety of retinal manifestations. We present an atypical case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment. Case Report A 26-year-old male with a genitourinary malformation and secondary grade IV chronic kidney failure as well as high blood pressure complained of acute vision loss. Dilated fundus examination evidenced a bilateral serous retinal detachment with macular involvement. The patient was unresponsive to oral antihypertensive therapy and dialysis treatment. The serous retinal detachment progressively decreased after the restoration of dialysis and antihypertensive therapy. The final visual acuity was 0.50 in both eyes. Discussion In cases of serous macular detachment, it is mandatory to rule out different systemic and ocular diseases. The presence of uncontrolled high blood pressure may produce aggressive bilateral retinal changes, thus hypertension must be under early and strict control in order to improve the visual outcomes. PMID:25120474

[Hypertensive crisis and posterior reversible encephalopathy syndrome (PRES)].

PubMed

Eberhardt, Olaf

2018-05-01

The urgency and intensity of therapeutic response to a hypertensive crisis are governed by the presence or absence of acute end-organ damage, which define hypertensive emergency and hypertensive urgency, respectively. In case of hypertensive urgency a slow and moderate lowering of blood pressure by oral antihypertensive agents seems adequate, while the approach to hypertensive emergency has to be tailored to the specific type of organ failure. Optimal blood pressure management in the context of neurovascular emergencies is made difficult by contradictory data from observational and interventional studies. It might prove advantageous to individualize treatment according to characteristics such as the location of persistent vessel occlusion or the presence of collaterals. Reversible posterior encephalopathy may present with atypical features that might make diagnosis difficult. Clevidipine might be a welcome supplement to current intravenous antihypertensive agents in neurological disease. Georg Thieme Verlag KG Stuttgart · New York.

Renal denervation for resistant hypertension using an irrigated radiofrequency balloon: 12-month results from the Renal Hypertension Ablation System (RHAS) trial.

PubMed

Ormiston, John A; Watson, Timothy; van Pelt, Niels; Stewart, Ralph; Stewart, James T; White, Jonathon M; Doughty, Robert N; Stewart, Fiona; Macdonald, Rhona; Webster, Mark W I

2013-05-20

Renal denervation using the point-by-point application of radiofrequency energy delivered by the first-generation Symplicity system is effective in lowering office blood pressure but may be time-consuming. The OneShot Renal Denervation System with a balloon-mounted spiral electrode potentially shortens and simplifies the procedure. This study is a hypothesis-generating first-in-human study to assess feasibility, and to provide preliminary efficacy and safety data. Eligible patients had a baseline office systolic blood pressure ≥160 mmHg (or ≥150 mmHg for diabetics) and were on two or more antihypertensive medications. Nine patients were enrolled. The primary endpoint, the insertion of the OneShot balloon into each renal artery and the delivery of radiofrequency energy, was achieved in 8/9 (89%) of patients. The one failure (the first patient) was due to generator high-impedance safety shut-off threshold set too low for humans. Adverse events were minor. No patient developed renal artery stenosis. Baseline BP was 185.67 ± 18.7 mmHg and the reductions at 1, 3, 6 and 12 months were 30.1 ± 13.6 (p=0.0004), 34.2 ± 20.2 (p=0.002), 33.6 ± 32.2 (p=0.021) and 30.6 ± 22.0 (p=0.019). The OneShot renal denervation system successfully delivered radiofrequency energy to the renal arteries in a short and straightforward procedure. Australian New Zealand Clinical Trials Registry - URL: anzctr.org.au. Trial identification: ACTRN12611000987965.

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

PubMed

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

2014-09-01

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

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

PubMed

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

2018-01-02

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

[Benefits and risks of hypertension therapy from the cardiac viewpoint].

PubMed

Motz, W; Strauer, B E

1994-03-01

The poor prognosis of arterial hypertension is mainly determined by its cardiac organ damages. Even borderline arterial hypertension significantly increases coronary morbidity and mortality, particularly in the presence of other risk factors such as hypercholesterolemia, diabetes, and cigarette smoking. Arterial hypertension causes myocardial hypertrophy and fibrosis, and affects coronary microcirculation by structural and functional changes of the small intramural resistance arteries, rarefiction of arterioles and capillaries and a distinct disturbance of endothelial vasomotion (i.e. "hypertensive remodeling"). Moreover, the presence of arterial hypertension predisposes to atherosclerotic coronary artery disease. Regarding the benefit-risk-ratio of antihypertensive therapy, benefit is much greater than risk: 1) An antihypertensive treatment with ACE-inhibitors, calcium channel blockers, beta-receptorblockers and anti-sympathicotonic substances leads to both reversal of LV hypertrophy and improvement of coronary flow reserve. Incidence of hypertensive heart failure has dropped considerably during the last 20 years. 3) Intervention studies have shown at least a clear tendency of a reduction in coronary morbidity and mortality. 4) In patients with coronary artery disease diastolic blood pressure should not be lowered under 85 mm Hg (J-curve). 5) An antihypertensive treatment should not adversely influence blood lipids when cholesterol is elevated. 6) Even in very elderly patients medical intervention to lower blood pressure is indicated from the cardiologic point of view (SHEP- and SHOP-studies).

Antihypertensive effect of a fixed-dose combination of losartan/hydrochlorothiazide in patients with uncontrolled hypertension: a multicenter study.

PubMed

Hosoya, Tatsuo; Kuriyama, Satoru; Ohno, Iwao; Kawamura, Tetsuya; Ogura, Makoto; Ikeda, Masato; Ishikawa, Masahiro; Hayashi, Fumihiro; Kanai, Tatsuya; Tomonari, Haruo; Soejima, Michimasa; Akaba, Kiyoaki; Tokudome, Goro; Endo, S; Fukui, A; Gomi, H; Hamaguchi, A; Hanaoka, K; Hara, Y; Hara, Y; Hasegawa, T; Hayakawa, H; Hikida, M; Hirano, K; Horiguchi, M; Hosoya, M; Ichida, K; Imai, T; Ishii, T; Ishikawa, H; Kameda, C; Kasai, T; Kobayashi, A; Kobayashi, H; Kurashige, M; Kusama, Y; Maezawa, H; Maezawa, Y; Maruyama, Y; Matsuda, H; Matsuo, N; Matsuo, T; Miura, Y; Miyajima, M; Miyakawa, M; Miyazaki, Y; Mizuguchi, M; Nakao, M; Nokano, H; Ohkido, I; Ohtsuka, Y; Okada, K; Okamoto, H; Okonogi, H; Saikawa, H; Saito, H; Sekiguchi, C; Suetsugu, Y; Sugano, N; Suzuki, T; Suzuki, T; Takahashi, H; Takahashi, Y; Takamizawa, S; Takane, K; Morita, T; Takazoe, K; Tanaka, H; Tanaka, S; Terawaki, H; Toyoshima, R; Tsuboi, N; Udagawa, T; Ueda, H; Ueda, Y; Uetake, M; Unemura, S; Utsunomiya, M; Utsunomiya, Y; Yamada, T; Yamada, Y; Yamaguchi, Y; Yamamoto, H; Yokoo, T; Yokoyama, K; Yonezawa, H; Yoshida, H; Yoshida, M; Yoshizawa, T

2012-04-01

Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension. The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study. A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value. Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

Effectiveness, safety and cost of drug substitution in hypertension

PubMed Central

Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

2010-01-01

Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the ‘inactive’ components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended. PMID:20716230

Effectiveness, safety and cost of drug substitution in hypertension.

PubMed

Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

2010-09-01

Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the 'inactive' components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended.

Effect of Frequent or Extended Hemodialysis on Cardiovascular Parameters: A Meta-analysis

PubMed Central

Susantitaphong, Paweena; Koulouridis, Ioannis; Balk, Ethan M.; Madias, Nicolaos E.; Jaber, Bertrand L.

2012-01-01

Background Increased left ventricular (LV) mass is a risk factor for cardiovascular mortality in patients with chronic kidney failure. More frequent or extended hemodialysis (HD) has been hypothesized to have a beneficial effect on LV mass. Study Design Meta-analysis. Setting & Population MEDLINE literature search (inception-April 2011), Cochrane Central Register of Controlled Trials and ClinicalTrials.gov using the search terms “short daily HD”, “daily HD”, “quotidian HD”, “frequent HD”, “intensive HD”, “nocturnal HD”, and “home HD”. Selection Criteria for Studies Single-arm cohort studies (with pre- and post-study evaluations) and randomized controlled trials examining the effect of frequent or extended HD on cardiac morphology and function, and blood pressure parameters. Studies of hemofiltration, hemodiafiltration and peritoneal dialysis were excluded. Intervention Frequent (2–8 hours,> thrice weekly) or extended (>4 hours, thrice weekly) HD as compared with conventional (≤ 4 hours, thrice weekly) HD. Outcomes Absolute changes in cardiac morphology and function, including LV mass index (LVMI) (primary), and blood pressure parameters (secondary). Results We identified 38 single-arm studies, 5 crossover trials and 3 randomized controlled trials. By meta-analysis of 23 study arms, frequent or extended HD significantly reduced LVMI from baseline (−31.2 g/m2, 95% CI, −39.8 to −22.5; P<0.001).The 3 randomized trials found a less pronounced net reduction in LVMI (−7.0 g/m2; 95% CI, −10.2 to −3.7; P<0.001). LV ejection fraction improved by 6.7% (95% CI, 1.6 to 11.9; P=0.01). Other cardiac morphological parameters displayed similar improvements. There were also significant decreases in systolic, diastolic, and mean blood pressure, and mean number of anti-hypertensive medications. Limitations Paucity of randomized controlled trials. Conclusions Conversion from conventional to frequent or extended HD is associated with an improvement in cardiac morphology and function, including LVMI and LV ejection fraction, respectively, and in several blood pressure parameters, which collectively might confer long-term cardiovascular benefit. Trials with long-term clinical outcomes are needed. PMID:22370022

Effects of a lifestyle programme on ambulatory blood pressure and drug dosage in treated hypertensive patients: a randomized controlled trial.

PubMed

Burke, Valerie; Beilin, Lawrie J; Cutt, Hayley E; Mansour, Jacqueline; Wilson, Amy; Mori, Trevor A

2005-06-01

To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals. Randomized controlled trial. Research studies unit. Overweight hypertensive patients, receiving one or two antihypertensive drugs, were recruited by advertising, and allocated randomly to a usual care group (controls; n = 118) or a lifestyle modification group (programme group; n = 123). A 4-month programme of weight loss, a low-sodium 'Dietary Approaches to Stop Hypertension'-type diet with added fish, physical activity and moderation of alcohol intake. After 4 months, if mean 24-h ambulatory blood pressure (ABP) was less than 135/85 mmHg, antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun. Antihypertensive drug requirements, ABP, weight, waist girth at 4 months and 1-year follow-up. Ninety control group and 102 programme group participants completed the study. Mean 24-h ABP changed after 4 months by -1.0/-0.3 +/- 0.5/0.4 mmHg in controls and -4.1/-2.1 +/- 0.7/0.5 mmHg with the lifestyle programme (P < 0.01). At follow-up, changes in the two groups were not significantly different (4.1/1.3 +/- 1.1/1.0 mmHg in controls; 2.5/-0.1 +/- 1.1/0.8 mmHg in the programme group; P = 0.73). At 4 months, drug withdrawal differed significantly between the groups (P = 0.038) in men (control 44%; programme 66%) but not in women (65 and 64%, respectively; P = 0.964). At follow-up, sex-related differences were not significant, and 41% in the control group and 43% in the programme group maintained drug-withdrawal status. With the programme, net weight loss was 3.3 kg (P < 0.001) at 4 months and 3.0 kg (P < 0.001) at follow-up; respective net decreases in waist girth were 3.3 cm (P < 0.001) and 3.5 cm (P < 0.001). A 4-month multifactorial lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term. Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk.

9C.03: THE BENEFIT FROM HEMODYNAMICALLY GUIDED ANTIHYPERTENSIVE THERAPY DEPENDS ON BASELINE BLOOD PRESSURE.

PubMed

Krzesinski, P; Gielerak, G; Stanczyk, A; Piotrowicz, K; Skrobowski, A

2015-06-01

Impedance cardiography (ICG) revealed to be useful in tailoring antihypertensive therapy to the patient's individual hemodynamic profile but little is known who benefits more from such therapeutic approach. The aim of this study was to estimate the effectiveness of ICG-guided antihypertensive therapy in 12-weeks observation with respect to baseline blood pressure (BP). This analysis involved 272 patients with untreated AH, recruited in two randomized, prospective and controlled trials (www.nauka-polska.pl: ID227062 and ClinicalTrials.gov: NCT01996085). After baseline evaluation including office blood pressure measurement (OBPM: OSBP, ODBP, OMBP) and ambulatory blood pressure monitoring (ABPM: 24-mean_SBP, 24-mean_DBP) the subjects were randomly assigned to groups of: [GE] empiric and [HD] ICG-guided antihypertensive therapy. The effectiveness of ICG-guided therapy was evaluated after 12 weeks in subgroups derived from median of OMBP (110 mmHg) of: higher (n = 120) and lower baseline OMBP (n = 121). The comparative analysis included absolute change of BP (d_OSBP, d_ODBP, d_24-mean_SBP, d_24-mean_DBP) and percentage of patients with change of BP equal or higher than 10 mmHg (d10_OSBP, d10_ODBP, d10_24-mean_SBP, d10_24-mean_DBP). In the whole study group the BP reduction in HD group was higher than in GE group: d_OSBP (18.3 vs. 14.3 mmHg; p = 0.011), d_ODBP (11.9 vs. 8.5 mmHg; p = 0.011), d_24-mean SBP (15.9 vs. 11.6 mmHg; p = 0.011) and d_24-mean SBP (10.4 vs. 8.9 mmHg; p = 0.147). However, the effect of ICG-guided therapy was significantly more pronounced in subjects with higher baseline OMBP - Table.(Figure is included in full-text article.) : The ICG-guided therapy effects with increased BP reduction in patients with AH, especially those with higher baseline BP. The patients with advanced AH can benefit more from individual these therapeutic approach.

Interventional procedures and future drug therapy for hypertension

PubMed Central

Lobo, Melvin D.; Sobotka, Paul A.; Pathak, Atul

2017-01-01

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. PMID:27406184

Rational Prescribing in Primary Care (RaPP): Economic Evaluation of an Intervention to Improve Professional Practice

PubMed Central

Fretheim, Atle; Aaserud, Morten; Oxman, Andrew D

2006-01-01

Background Interventions designed to narrow the gap between research findings and clinical practice may be effective, but also costly. Economic evaluations are necessary to judge whether such interventions are worth the effort. We have evaluated the economic effects of a tailored intervention to support the implementation of guidelines for the use of antihypertensive and cholesterol-lowering drugs. The tailored intervention was evaluated in a randomized trial, and was shown to significantly increase the use of thiazides for patients started on antihypertensive medication, but had little or no impact on other outcomes. The increased use of thiazides was not expected to have an impact on health outcomes. Methods and Findings We performed cost-minimization and cost-effectiveness analyses on data from a randomized trial involving 146 general practices from two geographical areas in Norway. Each practice was randomized to either the tailored intervention (70 practices; 257 physicians) or control group (69 practices; 244 physicians). Only patients that were being started on antihypertensive medication were included in the analyses. A multifaceted intervention was tailored to address identified barriers to change. Key components were an educational outreach visit with audit and feedback, and computerized reminders. Pharmacists conducted the visits. A cost-minimization framework was adopted, where the costs of intervention were set against the reduced treatment costs (principally due to increased use of thiazides rather than more expensive medication). The cost-effectiveness of the intervention was estimated as the cost per additional patient being started on thiazides. The net annual cost (cost minimization) in our study population was US$53,395, corresponding to US$763 per practice. The cost per additional patient started on thiazides (cost-effectiveness) was US$454. The net annual savings in a national program was modeled to be US$761,998, or US$540 per practice after 2 y. In this scenario the savings exceeded the costs in all but two of the sensitivity analyses we conducted, and the cost-effectiveness was estimated to be US$183. Conclusions We found a significant shift in prescribing of antihypertensive drugs towards the use of thiazides in our trial. A major reason to promote the use of thiazides is their lower price compared to other drugs. The cost of the intervention was more than twice the savings within the time frame of our study. However, we predict modest savings over a 2-y period. PMID:16737349

Calcium channel antagonists in the treatment of hypertension.

PubMed

Weber, Michael A

2002-01-01

Calcium channel antagonists are widely used antihypertensive agents. Their popularity among primary care physicians is not only due to their blood pressure-lowering effects, but also because they appear to be effective regardless of the age or ethnic background of the patients. The first available calcium channel antagonists utilized immediate-release formulations which, although effective in patients with angina pectoris, were not approved by the US FDA for use in hypertension. When long-acting once-daily formulations were approved in this indication, the short-acting preparations--which had by then become generic and inexpensive--retained some residual unapproved use for hypertension. An observational case-controlled trial, based on such usage, noted that these agents were associated with a greater risk of myocardial infarctions than conventional agents such as diuretics and beta-adrenoceptor antagonists. Further case-controlled trials showed, in fact, that the dangers of calcium channel antagonists were confined to the short-acting agents and that approved long-acting agents were at least as well tolerated and effective as other antihypertensive drugs. Cardiovascular outcomes during treatment with calcium channel antagonists have been examined in randomized, controlled trials. Compared with placebo, the calcium channel antagonists clearly prevented strokes and other cardiovascular events and reduced mortality. The effects of these agents on survival and clinical outcomes were similar to those with other antihypertensive drugs. There is a slight tendency for the calcium channel antagonists to be more effective than other drug types in preventing stroke, but slightly less effective in preventing coronary events. These observations extend to high-risk patients with hypertension including those with diabetes mellitus. Even so, patients with evidence of nephropathy should not receive monotherapy with calcium channel antagonists. Such patients are optimally treated with angiotensin receptor antagonists or ACE inhibitors, although addition of other drugs, including calcium channel antagonists, is often required to achieve the tight blood pressure control necessary to provide adequate renal protection. Calcium channel antagonists have a highly acceptable tolerability profile and careful reviews of available data have shown that their use is not associated with increased bleeding or promotion of tumor formation. It is now recognized that reduction of blood pressure in patients with hypertension to levels often <130/85 mm Hg should be undertaken in presence of other cardiovascular risk factors or evidence of end organ damage. Because of this important concept, calcium channel antagonists, like the other antihypertensive drug classes, are progressively being prescribed less often as monotherapy, but more typically as part of combination regimens.

Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial.

PubMed

Asher, Gary N; Viera, Anthony J; Weaver, Mark A; Dominik, Rosalie; Caughey, Melissa; Hinderliter, Alan L

2012-03-29

Hawthorn extract has been used for cardiovascular diseases for centuries. Recent trials have demonstrated its efficacy for the treatment of heart failure, and the results of several small trials suggest it may lower blood pressure. However, there is little published evidence to guide its dosing. The blood pressure lowering effect of hawthorn has been linked to nitric oxide-mediated vasodilation. The aim of this study was to investigate the relationship between hawthorn extract dose and brachial artery flow mediated dilation (FMD), an indirect measure of nitric oxide release. We used a four-period cross-over design to evaluate brachial artery FMD in response to placebo or hawthorn extract (standardized to 50 mg oligomeric procyanidin per 250 mg extract). Randomly sequenced doses of hawthorn extract (1000 mg, 1500 mg, and 2500 mg) and placebo were assigned to each participant. Doses were taken twice daily for 3 1/2 days followed by FMD and a 4-day washout before proceeding to the next dosing period. Twenty-one prehypertensive or mildly hypertensive adults completed the study. There was no evidence of a dose-response effect for our main outcome (FMD percent) or any of our secondary outcomes (absolute change in brachial artery diameter and blood pressure). Most participants indicated that if given evidence that hawthorn could lower their blood pressure, they would be likely to use it either in conjunction with or instead of lifestyle modification or anti-hypertensive medications. We found no evidence of a dose-response effect of hawthorn extract on FMD. If hawthorn has a blood pressure lowering effect, it is likely to be mediated via an NO-independent mechanism. This trial has been registered with ClinicalTrials.gov, a service of the U.S. National Institutes of Health: NCT01331486.

Novel ocular antihypertensive compounds in clinical trials

PubMed Central

Chen, June; Runyan, Stephen A; Robinson, Michael R

2011-01-01

Introduction: Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP) is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in glaucoma is associated with diminished or obstructed aqueous humor outflow. Pharmacotherapy reduces IOP by suppressing aqueous inflow and/or increasing aqueous outflow. Purpose: This review focuses on novel non-FDA approved ocular antihypertensive compounds being investigated for IOP reduction in ocular hypertensive and glaucoma patients in active clinical trials within approximately the past 2 years. Methods: The mode of IOP reduction, pharmacology, efficacy, and safety of these new agents were assessed. Relevant drug efficacy and safety trials were identified from searches of various scientific literature databases and clinical trial registries. Compounds with no specified drug class, insufficient background information, reformulations, and fixed-combinations of marketed drugs were not considered. Results: The investigational agents identified comprise those that act on the same targets of established drug classes approved by the FDA (ie, prostaglandin analogs and β-adrenergic blockers) as well as agents belonging to novel drug classes with unique mechanisms of action. Novel targets and compounds evaluated in clinical trials include an actin polymerization inhibitor (ie, latrunculin), Rho-associated protein kinase inhibitors, adenosine receptor analogs, an angiotensin II type 1 receptor antagonist, cannabinoid receptor agonists, and a serotonin receptor antagonist. Conclusion: The clinical value of novel compounds for the treatment of glaucoma will depend ultimately on demonstrating favorable efficacy and benefit-to-risk ratios relative to currently approved prostaglandin analogs and β-blockers and/or having complementary modes of action. PMID:21629573

Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

PubMed

Dewland, Thomas A; Soliman, Elsayed Z; Yamal, Jose-Miguel; Davis, Barry R; Alonso, Alvaro; Albert, Christine M; Simpson, Lara M; Haywood, L Julian; Marcus, Gregory M

2017-12-01

Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance. We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor. Participants were randomly assigned to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin versus usual care. The primary outcome was the development of either AF or AFL as diagnosed by serial study ECGs or by Medicare claims data. Among 14 837 participants without prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5±3.2 years of follow-up. Compared with chlorthalidone, randomization to either lisinopril (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; P =0.46) or amlodipine (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; P =0.16) was not associated with a significant reduction in incident AF/AFL. Compared with chlorthalidone, treatment with lisinopril is not associated with a meaningful reduction in incident AF or AFL among older adults with a history of hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542. © 2017 American Heart Association, Inc.

White-Coat Effect Is Uncommon in Patients With Refractory Hypertension.

PubMed

Siddiqui, Mohammed; Judd, Eric K; Oparil, Suzanne; Calhoun, David A

2017-09-01

Refractory hypertension is a recently described phenotype of antihypertensive treatment failure defined as uncontrolled blood pressure (BP) despite the use of ≥5 different antihypertensive agents, including chlorthalidone and spironolactone. Recent studies indicate that refractory hypertension is uncommon, with a prevalence of ≈5% to 10% of patients referred to a hypertension specialty clinic for uncontrolled hypertension. The prevalence of white-coat effect, that is, uncontrolled automated office BP ≥135/85 mm Hg and controlled out-of-office BP <135/85 mm Hg, by awake ambulatory BP monitor in hypertensive patients overall is ≈30% to 40%. The prevalence of white-coat effect among patients with refractory hypertension has not been previously reported. In this prospective evaluation, consecutive patients referred to the University of Alabama at Birmingham Hypertension Clinic for uncontrolled hypertension were enrolled. Refractory hypertension was defined as uncontrolled automated office BP ≥135/85 mm Hg with the use of ≥5 antihypertensive agents, including chlorthalidone and spironolactone. Automated office BP measurements were based on 6 serial readings, done automatically with the use of a BpTRU device unobserved in the clinic. Out-of-office BP measurements were done by 24-hour ambulatory BP monitor. Thirty-four patients were diagnosed with refractory hypertension, of whom 31 had adequate ambulatory BP monitor readings. White-coat effect was present in only 2 patients, or 6.5% of the 31 patients with refractory hypertension, suggesting that white-coat effect is largely absent in patients with refractory hypertension. These findings suggest that white-coat effect is not a common cause of apparent lack of BP control in patients failing maximal antihypertensive treatment. © 2017 American Heart Association, Inc.

Visit-to-visit variability of blood pressure and coronary heart disease, stroke, heart failure and mortality: A cohort study

PubMed Central

Muntner, Paul; Whittle, Jeff; Lynch, Amy I.; Colantonio, Lisandro D.; Simpson, Lara M.; Einhorn, Paula T.; Levitan, Emily B.; Whelton, Paul K; Cushman, William C.; Louis, Gail T.; Davis, Barry R.; Oparil, Suzanne

2016-01-01

Background Variability of blood pressure (BP) across outpatient visits is frequently dismissed as random fluctuation around a patient’s underlying BP. Objective: Examine the association between visit-to-visit variability (VVV) of systolic and diastolic BP (SBP and DBP) on cardiovascular disease and mortality outcomes. Design Prospective cohort study Setting Post-hoc analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Participants 25,814 ALLHAT participants. Measurements VVV of SBP was defined as the standard deviation (SD) across BP measurements obtained at 7 visits conducted from 6 to 28 months following ALLHAT enrollment. Participants free of cardiovascular disease events during the first 28 months of follow-up were followed from the month 28 study visit through the end of active ALLHAT follow-up. Outcomes included fatal coronary heart disease or non-fatal myocardial infarction, all-cause mortality, stroke and heart failure. Results There were 1194 cases of fatal CHD or non-fatal MI, 1948 deaths, 606 cases of stroke and 921 cases of heart failure during follow-up. After multivariable adjustment including mean SBP, the hazard ratio comparing participants in the highest versus lowest quintile of SD of SBP (≥14.4 mmHg versus <6.5 mmHg) was 1.30 (1.06–1.59) for fatal coronary heart disease or non-fatal myocardial infarction, 1.58 (1.32–1.90) for all-cause mortality, 1.46 (1.06–2.01) for stroke, and 1.25 (0.97–1.61) for heart failure. Higher VVV of DBP was also associated with cardiovascular disease events and mortality. Limitations Long-term outcomes were not available. Conclusions Higher VVV of SBP is associated with increased cardiovascular disease and mortality risk. Future studies should examine whether reducing VVV of BP lowers this risk. Primary funding source National Institutes of Health PMID:26215765

Effect of aspirin in pregnant women is dependent on increase in bleeding time.

PubMed

Dumont, A; Flahault, A; Beaufils, M; Verdy, E; Uzan, S

1999-01-01

Randomized trials with low-dose aspirin to prevent preeclampsia and intrauterine growth restriction have yielded conflicting results. In particular, 3 recent large trials were not conclusive. Study designs, however, varied greatly regarding selection of patients, dose of aspirin, and timing of treatment, all of which can be determinants of the results. Retrospectively analyzing the conditions associated with failure or success of aspirin may therefore help to draw up new hypotheses and prepare for more specific randomized trials. We studied a historical cohort of 187 pregnant women who were considered at high risk for preeclampsia, intrauterine growth restriction, or both and were therefore treated with low-dose aspirin between 1989 and 1994. Various epidemiologic, clinical, and laboratory data were extracted from the files. Univariate and multivariate analyses were performed to search for independent parameters associated with the outcome of pregnancy. Age, parity, weight, height, and race had no influence on the outcome. The success rate was higher when treatment was given because of previous poor pregnancy outcomes than when it was given for other indications, and the patients with successful therapy had started aspirin earlier than had those with therapy failure (17.7 vs 20.0 weeks' gestation, P =.04). After multivariate analysis an increase in Ivy bleeding time after 10 days of treatment by >2 minutes was an independent predictor of a better outcome (odds ratio 0.22, 95% confidence interval 0.09-0.51). Borderline statistical significance was observed for aspirin initiation before 17 weeks' gestation (odds ratio 0.44, 95% confidence interval 0.18-1. 08). Abnormal uterine artery Doppler velocimetric scan at 20-24 weeks' gestation (odds ratio 3.31, 95% confidence interval 1.41-7.7), abnormal umbilical artery Doppler velocimetric scan after 26 weeks' gestation (odds ratio 37.6, 95% confidence interval 3.96-357), and use of antihypertensive therapy (odds ratio 6.06, 95% confidence interval 2.45-15) were independent predictors of poor outcome. Efficacy of aspirin seems optimal when bleeding time increases >/=2 minutes with treatment, indicating a more powerful antiplatelet effect. This suggests that the dose of aspirin should be adjusted according to a biologic marker of the antiplatelet effect. A prospective trial is warranted to test this hypothesis.

Refractory Hypertension Is not Attributable to Intravascular Fluid Retention as Determined by Intracardiac Volumes.

PubMed

Velasco, Alejandro; Siddiqui, Mohammed; Kreps, Eric; Kolakalapudi, Pavani; Dudenbostel, Tanja; Arora, Garima; Judd, Eric K; Prabhu, Sumanth D; Lloyd, Steven G; Oparil, Suzanne; Calhoun, David A

2018-06-04

Refractory hypertension (RfHTN) is an extreme phenotype of antihypertensive treatment failure defined as lack of blood pressure control with ≥5 medications, including a long-acting thiazide and a mineralocorticoid receptor antagonist. RfHTN is a subgroup of resistant hypertension (RHTN), which is defined as blood pressure >135/85 mm Hg with ≥3 antihypertensive medications, including a diuretic. RHTN is generally attributed to persistent intravascular fluid retention. It is unknown whether alternative mechanisms are operative in RfHTN. Our objective was to determine whether RfHTN is characterized by persistent fluid retention, indexed by greater intracardiac volumes determined by cardiac magnetic resonance when compared with controlled RHTN patients. Consecutive patients evaluated in our institution with RfHTN and controlled RHTN were prospectively enrolled. Exclusion criteria included advanced chronic kidney disease and masked or white coat hypertension. All enrolled patients underwent biochemical testing and cardiac magnetic resonance. The RfHTN group (n=24) was younger (mean age, 51.7±8.9 versus 60.6±11.5 years; P =0.003) and had a greater proportion of women (75.0% versus 43%; P =0.02) compared with the controlled RHTN group (n=30). RfHTN patients had a greater left ventricular mass index (88.3±35.0 versus 54.6±12.5 g/m 2 ; P <0.001), posterior wall thickness (10.1±3.1 versus 7.7±1.5 mm; P =0.001), and septal wall thickness (14.5±3.8 versus 10.0±2.2 mm; P <0.001). There was no difference in B-type natriuretic peptide levels and left atrial or ventricular volumes. Diastolic dysfunction was noted in RfHTN. Our findings demonstrate greater left ventricular hypertrophy without chamber enlargement in RfHTN, suggesting that antihypertensive treatment failure is not attributable to intravascular volume retention. © 2018 American Heart Association, Inc.

Impact of Clinical Factors on the Achievement of Target Blood Pressure in Hypertensive Patients from Ivanovo Region of Russia: Data of 2015.

PubMed

Kiselev, A R; Posnenkova, O M; Belova, O A; Romanchuk, S V; Popova, Y V; Prokhorov, M D; Gridnev, V I

2017-12-01

In Russia, blood pressure (BP) control is below the optimal. The little is known about regional features and barriers to adequate BP control in Russian primary care. To evaluate the impact of clinical factors on achieving the target BP in hypertensive patients in one region of Russia. Retrospective medical data of 2015 on 11,129 patients (31.4% male) with hypertension (Htn) from Ivanovo region of Russia were examined. Achievement of target BP was assessed in all patients. We study association between BP control and clinical factors. 45.9% of studied patients with Htn had controlled BP. The frequency of achieving the target BP in subsets of hypertensive patients was 37.8% in patients with diabetes, 39.5% in patients with coronary artery disease, and 29.9% in patients with chronic heart failure. The main clinical factors associated with achieving the target BP in studied hypertensive patients were the advice on alcohol consumption, advice on smoking cessation, and advice on weight reduction. Therapy with main antihypertensive drugs (in particular, beta-blockers and thiazide diuretics) were also factors of optimal BP control in these patients. Comorbidities (chronic heart failure and cardiovascular diseases requiring the prescription of aspirin and statins) and family history of coronary artery disease were associated with inadequate BP control. A negative effect of some antihypertensive drugs (potassium sparing diuretics, ARBs, ACE-Is, and dihydropyridine CCBs) on BP control that was found out in our study requires further investigation. Other studied factors had no influence on BP control in patients with Htn from Ivanovo region. We identified regional factors of BP control in hypertensive patients from Ivanovo region of Russia. It is shown that individual medical education (in particular, medical advices) is the most important factor of optimal BP control. The intervention with antihypertensive therapy (beta-blockers and thiazide diuretics) facilitates the achievement of target BP. Comorbidity and age reduce the frequency of achieving the target BP.

Home blood pressure monitoring and self-titration of antihypertensive medications: Proposed patient selection criteria.

PubMed

Hill, James R

2016-05-01

Recent studies have demonstrated that home blood pressure monitoring (HBPM), coupled with self-titration of medications is a viable intervention to control hypertension. There are currently no established criteria to evaluate patients for inclusion in such a program. The purpose of this discussion is to propose criteria for determining if a patient is appropriate to participate in a program of HBPM and self-titration. Inclusion criteria for two self-titration trials were examined, and additional factors in clinical practice were identified and discussed. Additional selection criteria were proposed to support the decision to enroll a patient in an antihypertensive self-titration program. Inclusion criteria from self-titration trials provide a reasonable starting point for choosing appropriate patients in clinical practice, but additional research is necessary. Adaptation of these criteria and consideration of the identified factors can be used to develop decision support instruments. Such instruments should be evaluated for effectiveness and reliability prior to use in clinical practice. HBPM combined with self-titration is an effective patient-centered approach for hypertension management. Decision support instruments to determine appropriate patients are necessary for safe and effective use in clinical practice. ©2015 American Association of Nurse Practitioners.

An analysis of the blood pressure and safety outcomes to renal denervation in African Americans and Non-African Americans in the SYMPLICITY HTN-3 trial.

PubMed

Flack, John M; Bhatt, Deepak L; Kandzari, David E; Brown, David; Brar, Sandeep; Choi, James W; D'Agostino, Ralph; East, Cara; Katzen, Barry T; Lee, Lilian; Leon, Martin B; Mauri, Laura; O'Neill, William W; Oparil, Suzanne; Rocha-Singh, Krishna; Townsend, Raymond R; Bakris, George

2015-10-01

SYMPLICITY HTN-3, the first trial of renal denervation (RDN) versus sham, enrolled 26% African Americans, a prospectively stratified cohort. Although the 6-month systolic blood pressure (SBP) reduction in African Americans (AAs) was similar in the RDN group (-15.5 ± 25.4 mm Hg, n = 85 vs. -17.8 ± 29.2, n = 49, P = .641), the sham SBP response was 9.2 mm Hg greater (P = .057) in AAs than non-AAs. In multivariate analyses, sham SBP response was predicted by an interaction between AA and a complex antihypertensive regimen (at least one antihypertensive medication prescribed ≥3 times daily), while in the RDN group, SBP response was predicted by an interaction between AA race and baseline BP ≥ 180 mm Hg. AA race did not independently predict SBP response in either sham or RDN. There appears to be effect modification by race with individual-level patient characteristics in both treatment arms that affect the observed pattern of SBP responses. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Revisiting RAAS blockade in CKD with newer potassium-binding drugs.

PubMed

Georgianos, Panagiotis I; Agarwal, Rajiv

2018-02-01

Among patients with proteinuric chronic kidney disease (CKD), current guideline recommendations mandate the use of agents blocking the renin angiotensin aldosterone system (RAAS) as first-line antihypertensive therapy based on randomized trials demonstrating that RAAS inhibitors are superior to other antihypertensive drug classes in slowing nephropathy progression to end-stage renal disease. However, the opportunities for adequate RAAS blockade in CKD are often limited, and an important impediment is the risk of hyperkalemia, especially when RAAS inhibitors are used in maximal doses or are combined. Accordingly, a large proportion of patients with proteinuric CKD may not have the anticipated renoprotective benefits since RAAS blockers are often discontinued due to incident hyperkalemia or are administered at suboptimal doses for fear of the development of hyperkalemia. Two newer potassium binders, patiromer and sodium zirconium cyclosilicate (ZS-9), have been shown to effectively and safely reduce serum potassium levels and maintain long-term normokalemia in CKD patients receiving background therapy with RAAS inhibitors. Whether these novel potassium-lowering therapies can overcome the barrier of hyperkalemia and enhance the tolerability of RAAS inhibitor use in proteinuric CKD awaits randomized trials. Published by Elsevier Inc.

Management of Acute Hypertensive Response in Intracerebral Hemorrhage Patients After ATACH-2 Trial.

PubMed

Majidi, Shahram; Suarez, Jose I; Qureshi, Adnan I

2017-10-01

Acute hypertensive response is elevation of systolic blood pressure (SBP) in the first 24 h after symptom onset which is highly prevalent in patients with intracerebral hemorrhage (ICH). Observational studies suggested association between acute hypertensive response and hematoma expansion, peri-hematoma edema and death and disability, and possible reduction in these adverse outcomes with treatment of acute hypertensive response. Recent clinical trials have focused on determining the clinical efficacy of early intensive SBP reduction in ICH patients. The Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-2) trial was the latest phase 3 randomized controlled multicenter clinical trial aimed to study the efficacy of early intensive reduction of SBP in ICH patients. In this review article, we summarize the results of recent clinical trials, treatment principles based on the latest guidelines, and the anticipated interpretation and incorporation of ATACH-2 trial results in clinical practice.

Protocol of randomized control trial for effectiveness of angiotensin receptor blockers on blood pressure control among euvolemic hypertensive hemodialysis patients

PubMed Central

Aftab, Raja Ahsan; Khan, Amer Hayat; Syed Sulaiman, Syed Azhar; Khan, Tahir Mehmood; Adnan, Azreen Syazril

2017-01-01

Abstract Introduction: Volume overload and the renin–aldosterone–angiotensin system (RAAS) are 2 major factors contributing to hypertension (HTN) among hemodialysis (HD) patients. Although volume-dependent components of HTN can be corrected by appropriate volume removal, a proportion of HD patients experience elevated blood pressure (BP) despite achieving euvolemic and ideal dry weight. Method and analysis: A single center, prospective, randomized, parallel design, single-blind trial will be conducted in the Malaysian state of Kelantan among postdialysis euvolemic hypertensive patients that are on regular dialysis at least 3 times a week. The primary outcome of the trial will be to note the effectiveness of losartan (RAAS inhibitor) in reducing systolic BP < 140 mm Hg compared to standard non-RAAS-inhibitor antihypertensive therapy. The secondary outcome will be to look at all causes of mortality. A body composition monitor (BCM) will be used to assess postdialysis volume and dry weight. Postdialysis euvolemic patients that have systolic BP > 140 mm Hg will be randomized using Covariate Adaptive Randomization to standard or treatment arm. Participants in the treatment arm will be given 50 mg of losartan once daily except on dialysis days, whereas the standard arm patients will be prescribed non-RAAS antihypertensive agents. The study participants will be followed for a period of 12 months. A Wilcoxon statistical test will be performed to note the difference in BP from baseline up to 12 months using Statistical Package for the Social Sciences (SPSS) 20. Ethical and trial registration: The study protocols are approved from the Ethical and Research Committee of the Universiti Sains Malaysia (USM/JEPeM/15050173). The trial is registered under the Australia New Zealand Clinical Trial Registry (ACTRN12615001322527). The trial was registered on 2/12/2015 and the 1st patient was enrolled on 10/12/2015. The trial was formally initiated on 16/02/2016. Conclusion: Management of HTN among HD patients requires understanding the primary cause of HTN and treating accordingly. The current trial is an attempt to reduce BP among postdialysis euvolemic but hypertensive patients. PMID:28383400

Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women’s Health Initiative Memory Study

PubMed Central

Wu, Chunyuan; Coker, Laura H.; Seth, Arjun; Snetselaar, Linda; Manson, JoAnn E.; Rossouw, Jacques E.; Wassertheil-Smoller, Sylvia

2016-01-01

BACKGROUND To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. METHODS Prospective follow-up of 6,426 cognitively intact women aged 65–79 years enrolled in the Women’s Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140mm Hg or diastolic BP ≥ 90mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). RESULTS Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP ≥140/90mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). CONCLUSIONS Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056 PMID:26137952

Influence of autoantibodies against AT1 receptor and AGTR1 polymorphisms on candesartan-based antihypertensive regimen: results from the study of optimal treatment in hypertensive patients with anti-AT1-receptor autoantibodies trial.

PubMed

Sun, Yanxiang; Liao, Yuhua; Yuan, Yong; Feng, Li; Ma, Shihui; Wei, Feng; Wang, Min; Zhu, Feng

2014-01-01

The autoantibodies against angiotensin AT1 receptors (AT1-AAs) in patients with essential hypertension exhibited an agonistic action like angiotensin II and maintained high blood pressure (BP). Angiotensin II receptor gene (AGTR1) polymorphisms were associated with BP response to RAS inhibition in the hypertensive population. Furthermore, the BP response to AT1 receptor blockers varied significantly among individuals with hypertension. We hypothesized that the polymorphisms of the AGTR1 and AT1-AAs might affect antihypertensive response to AT1 receptor blockers based in patients with primary hypertension. Patients who received a candesartan-based regimen came from the SOT-AT1 study (Study of Optimal Treatment in Hypertensive Patients with Anti-AT1-Receptor Autoantibodies). The established enzyme-labeled immunosorbent assay was used to detect AT1-AAs in the sera of the patients. Genotype 3 single nucleotide polymorphisms in AGTR1 gene was used by DNA sequencing. The correlations among AT1-AAs, AGTR1 gene polymorphisms or haplotypes, and the antihypertensive effect candesartan-based were analyzed using SPSS. The percentage of systolic BP reduction that was candesartan-based was greater in AT1-AA positive groups than in AT1-AA negative ones (21 ± 8 vs. 18 ± 9; P = .001). Meanwhile, systolic BP reduction that was candesartan-based was more significant in the group of rs5186 AC genotypes than AA homozygotes after adjusting for other confounding factors (37.55 ± 13.7 vs. 32.47 ± 17.27 mm Hg; adjusted P = .028). Furthermore, haplotypes (GCC) and (AAC) had impacts on the antihypertensive effect of candesartan therapy. The AT1-AAs, AGTR1 gene polymorphisms and haplotypes solely or jointly have influences on candesartan-based antihypertensive response in patients with primary hypertension. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Impact of Empagliflozin on Blood Pressure in Patients With Type 2 Diabetes Mellitus and Hypertension by Background Antihypertensive Medication.

PubMed

Mancia, Giuseppe; Cannon, Christopher P; Tikkanen, Ilkka; Zeller, Cordula; Ley, Ludwin; Woerle, Hans J; Broedl, Uli C; Johansen, Odd Erik

2016-12-01

In the EMPA-REG BP trial, empagliflozin 10 mg and 25 mg once daily reduced glycohemoglobin, blood pressure (BP), and weight versus placebo in patients with type 2 diabetes mellitus and hypertension. Patients received placebo (n=271), empagliflozin 10 mg (n=276), or empagliflozin 25 mg (n=276) for 12 weeks (n=full analysis set). This present analysis investigated changes from baseline to week 12 in mean 24-hour systolic BP (SBP) and diastolic BP (DBP) in patients receiving 0, 1, or ≥2 antihypertensive medications and patients receiving/not receiving diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Compared with placebo, empagliflozin 10 mg and 25 mg reduced mean 24-hour SBP/DBP in patients receiving 0 (10 mg: -3.89/-2.58 mm Hg; 25 mg: -3.77/-2.45 mm Hg), 1 (10 mg: -4.74/-1.97 mm Hg; 25 mg: -4.27/-1.81 mm Hg), or ≥2 (10 mg: -2.36/-0.68 mm Hg; 25 mg: -4.17/-1.54 mm Hg) antihypertensives. The effect of empagliflozin was not significantly different between subgroups by number of antihypertensives for changes in SBP (interaction P value 0.448) or DBP (interaction P value 0.498). Empagliflozin reduced 24-hour mean SBP/DBP irrespective of diuretic or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, with no significant difference between subgroups by use/no use of diuretics (interaction P values 0.380 [systolic]; 0.240 [diastolic]) or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (interaction P values 0.900 [systolic]; 0.359 [diastolic]). In conclusion, in patients with type 2 diabetes mellitus and hypertension, empagliflozin for 12 weeks reduced SBP and DBP versus placebo, irrespective of the number of antihypertensives and use of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. URL: https://clinicaltrials.gov. Unique identifier: NCT01370005. © 2016 American Heart Association, Inc.

Atrial fibrillation and isolated systolic hypertension: the systolic hypertension in the elderly program and systolic hypertension in the elderly program-extension study.

PubMed

Vagaonescu, Tudor D; Wilson, Alan C; Kostis, John B

2008-06-01

We performed a post hoc analysis of the Systolic Hypertension in the Elderly Program database to assess the incidence of atrial fibrillation in the elderly hypertensive population, its influence on cardiovascular events, and whether antihypertensive treatment can prevent its onset. The Systolic Hypertension in the Elderly Program was a double-blind placebo-controlled trial in 4736 subjects with isolated systolic hypertension aged >or=60 years. Atrial fibrillation was an exclusion criterion from the trial. Participants were randomly assigned to stepped care treatment with chlorthalidone and atenolol (n=2365) or placebo (n=2371). The occurrence of atrial fibrillation and cardiovascular events over 4.7 years as well as the determination of cause of death at 4.7 and 14.3 years were followed. Ninety-eight subjects (2.06%) developed atrial fibrillation over 4.7 years mean follow-up, without significant difference between treated and placebo groups. Atrial fibrillation increased the risk for: total cardiovascular events (RR 1.69; 95% CI 1.21 to 2.36), rapid death (RR 3.29; 95% CI 1.08 to 10.00), total (RR 5.10; 95% CI 3.12 to 8.37) and nonfatal left ventricular failure (RR 5.31; 95% CI 3.09 to 9.13). All-cause and total cardiovascular death were significantly increased in the atrial fibrillation group at 4.7 years (HR 3.44; 95% CI 2.18 to 5.42; HR 2.39; 95% CI 1.05 to 5.43) and 14.3 years follow-up (HR 2.33; 95% CI 1.83 to 2.98; HR 2.21; 95% CI 1.54 to 3.17). Atrial fibrillation increased the risk for total cardiovascular events, rapid death, and left ventricular failure. All-cause mortality and total cardiovascular mortality were significantly increased in hypertensives with atrial fibrillation at 4.7 and 14.3 years follow-up.

Efficacy of self-monitored blood pressure, with or without telemonitoring, for titration of antihypertensive medication (TASMINH4): an unmasked randomised controlled trial.

PubMed

McManus, Richard J; Mant, Jonathan; Franssen, Marloes; Nickless, Alecia; Schwartz, Claire; Hodgkinson, James; Bradburn, Peter; Farmer, Andrew; Grant, Sabrina; Greenfield, Sheila M; Heneghan, Carl; Jowett, Susan; Martin, Una; Milner, Siobhan; Monahan, Mark; Mort, Sam; Ogburn, Emma; Perera-Salazar, Rafael; Shah, Syed Ahmar; Yu, Ly-Mee; Tarassenko, Lionel; Hobbs, F D Richard

2018-03-10

Studies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care. This study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mm Hg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisation was by a secure web-based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pressure at 12 months from randomisation. Primary analysis was of available cases. The trial is registered with ISRCTN, number ISRCTN 83571366. 1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 [SD 16·7] mm Hg and telemonitoring, 136·0 [16·1] mm Hg vs usual care, 140·4 [16·5]; adjusted mean differences vs usual care: self-monitoring alone, -3·5 mm Hg [95% CI -5·8 to -1·2]; telemonitoring, -4·7 mm Hg [-7·0 to -2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference -1·2 mm Hg [95% CI -3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups. Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care. National Institute for Health Research via Programme Grant for Applied Health Research (RP-PG-1209-10051), Professorship to RJM (NIHR-RP-R2-12-015), Oxford Collaboration for Leadership in Applied Health Research and Care, and Omron Healthcare UK. 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.

Bioactive natural constituents from food sources-potential use in hypertension prevention and treatment.

PubMed

Huang, Wu-Yang; Davidge, Sandra T; Wu, Jianping

2013-01-01

Prevention and management of hypertension are the major public health challenges worldwide. Uncontrolled high blood pressure may lead to a shortened life expectancy and a higher morbidity due to a high risk of cardiovascular complications such as coronary heart disease (which leads to heart attack) and stroke, congestive heart failure, heart rhythm irregularities, and kidney failure etc. In recent years, it has been recognized that many dietary constituents may contribute to human cardiovascular health. There has been an increased focus on identifying these natural components of foods, describing their physiological activities and mechanisms of actions. Grain, vegetables, fruits, milk, cheese, meat, chicken, egg, fish, soybean, tea, wine, mushrooms, and lactic acid bacteria are various food sources with potential antihypertensive effects. Their main bioactive constituents include angiotensin I-converting enzyme (ACE) inhibitory peptides, vitamins C and E, flavonoids, flavanols, cathecins, anthocyanins, phenolic acids, polyphenols, tannins, resveratrol, polysaccharides, fiber, saponin, sterols, as well as K, Ca, and P. They may reduce blood pressure by different mechanisms, such as ACE inhibition effect, antioxidant, vasodilatory, opiate-like, Ca(2+) channel blocking, and chymase inhibitory activities. These functional foods may provide new therapeutic applications for hypertension prevention and treatment, and contribute to a healthy cardiovascular population. The present review summarizes the antihypertensive food sources and their bioactive constituents, as well as physiological mechanisms of dietary products, especially focusing on ACE inhibitory activity.

Assessing outcomes to determine whether symptoms related to hypertension justify renal artery stenting.

PubMed

Modrall, J Gregory; Rosero, Eric B; Timaran, Carlos H; Anthony, Thomas; Chung, Jayer; Valentine, R James; Trimmer, Clayton

2012-02-01

The goal of the study was to determine the blood pressure (BP) response to renal artery stenting (RAS) for patients with hypertension urgency, hypertension emergency, and angina with congestive heart failure (angina/congestive heart failure [CHF]). Patients who underwent RAS for hypertension emergencies (n = 13), hypertension urgencies (n = 25), and angina/CHF (n = 14) were included in the analysis. By convention, hypertension urgency was defined by a sustained systolic BP ≥ 180 mm Hg or diastolic BP ≥ 120 mm Hg, while the definition of hypertension emergency required the same BP parameters plus hypertension-related symptoms prompting hospitalization. Patient-specific response to RAS was defined according to modified American Heart Association reporting guidelines. The study cohort of 52 patients had a median age of 66 years (interquartile range 58-72). The BP response to RAS varied significantly according to the indication for RAS. Hypertension emergency provided the highest BP response rate (85%), while the response rate was significantly lower for hypertension urgency (52%) and angina/CHF (7%; P = .03). Only 1 of 14 patients with angina/CHF was a BP responder. Multivariate analysis showed that hypertension urgency or emergency were not independent predictors of BP response to RAS. Instead, the only independent predictor of a favorable BP response was the number of preoperative antihypertensive medications (odds ratio 7.5; 95% confidence interval 2.5-22.9; P = .0004), which is another indicator of the severity of hypertension. Angina/CHF was an independent predictor of failure to respond to RAS (odds ratio 118.6; 95% confidence interval 2.8-999.9; P = .013). Hypertension urgency and emergency are clinical manifestations of severe hypertension, but the number of preoperative antihypertensive medications proved to be a better predictor of a favorable BP response to RAS. In contrast, angina/CHF was a predictor of failure to respond to stenting, providing further evidence against the practice of incidental stenting during coronary interventions. Copyright © 2012 Society for Vascular Surgery. All rights reserved.

Nebivolol: impact on cardiac and endothelial function and clinical utility.

PubMed

Toblli, Jorge Eduardo; DiGennaro, Federico; Giani, Jorge Fernando; Dominici, Fernando Pablo

2012-01-01

Endothelial dysfunction is a systemic pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as disarrangement in vascular wall metabolism and function. One of the key factors in endothelial dysfunction is overproduction of reactive oxygen species which participate in the development of hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke. Because impaired endothelial activity is believed to have a major causal role in the pathophysiology of vascular disease, hypertension, and heart failure, therapeutic agents which modify this condition are of clinical interest. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenergic receptors and causes vasodilation by interaction with the endothelial L-arginine/ nitric oxide pathway. This dual mechanism of action underscores several hemodynamic qualities of nebivolol, which include reductions in heart rate and blood pressure and improvements in systolic and diastolic function. Although nebivolol reduces blood pressure to a degree similar to that of conventional β-blockers and other types of antihypertensive drugs, it may have advantages in populations with difficult-to-treat hypertension, such as patients with heart failure along with other comorbidities, like diabetes and obesity, and elderly patients in whom nitric oxide-mediated endothelial dysfunction may be more pronounced. Furthermore, recent data indicate that nebivolol appears to be a cost-effective treatment for elderly patients with heart failure compared with standard care. Thus, nebivolol is an effective and well tolerated agent with benefits above those of traditional β-blockers due to its influence on nitric oxide release, which give it singular hemodynamic effects, cardioprotective activity, and a good tolerability profile. This paper reviews the pharmacology structure and properties of nebivolol, focusing on endothelial dysfunction, clinical utility, comparative efficacy, side effects, and quality of life in general with respect to the other antihypertensive agents.

Two cases of malignant hypertension with reversible diffuse leukoencephalopathy exhibiting a reversible nocturnal blood pressure "riser" pattern.

PubMed

Eguchi, Kazuo; Kasahara, Kentaro; Nagashima, Akinori; Mor, Tadashi; Nii, Takanobu; Ibaraki, Kazuo; Kario, Kazuomi; Shimada, Kazuyuki

2002-05-01

We report two cases of malignant hypertension with reversible diffuse leukoencephalopathy demonstrating a nocturnal blood pressure (BP) rising pattern ("riser" pattern). Case 1 was a 54-year-old man diagnosed with malignant hypertension who presented with diffuse leukoencephalopathy and nocturnal BP rise during the acute phase. These abnormal findings diminished after treatment of hypertension. Case 2 was a 50-year-old woman diagnosed with malignant hypertension in association with leukoencephalopathy, heart failure and acute renal failure. She also presented with a "riser" pattern during the acute phase. In contrast to case 1, the leukoencephalopathy and "riser" pattern in case 2 were not improved even after 1 month of treatment. Following intensive antihypertensive treatment, renal failure was improved in case 1, but renal failure was not improved after 1 month in case 2. In conclusion, a possible explanation of this phenomenon is that a causative volume overload due to renal dysfunction produced the temporal leukoencephalopathy-like brain edema and "riser" pattern in these cases.

Guide of Hypertensive Crisis Pharmacotherapy.

PubMed

Wani-Parekh, Priyanka; Blanco-Garcia, Carlos; Mendez, Melissa; Mukherjee, Debabrata

2017-01-01

Cardiovascular diseases (CVD) are the number one cause of death globally compared to any other cause. CVD accounts for approximately 17.3 million deaths per year and are rising. Hypertension is the leading risk factor for cardiovascular diseases. Approximately, 80 million people suffer from hypertension in the U.S. While, majority of these individuals are on antihypertensive medications only 54% of individuals with hypertension are optimally controlled. Heart failure and stroke are some of the devastating complications of uncontrolled hypertension. Hypertensive crisis can be classified as either an urgency or emergency; difference between the two is the presence of end organ damage, which is noted in hypertensive emergency. Hypertensive crisis is usually treated by parenteral antihypertensive medications. The main drug classes of drugs for treatment are nitrates, calcium channel blockers, dopamine-1 agonists, adrenergic-blocking agents etc. In this review, we discuss approach to management of hypertensive crisis and each drug class with its physiology and complications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antihypertensive efficacy and tolerability of lercanidipine in daily clinical practice. The ELYPSE Study. Eficacia de Lercanidipino y su Perfil de Seguridad.

PubMed

Barrios, Vivencio; Navarro, Angel; Esteras, Antonio; Luque, Manuel; Romero, Joaquima; Tamargo, Juan; Prieto, Luis; Carrasco, Jose Luis; Herranz, Inmaculada; Navarro-Cid, Josefa; Ruilope, Luis M

2002-01-01

Lercanidipine, a long-acting dihydropyridine with a good antihypertensive efficacy and tolerability in clinical use. With the aim to determine the efficacy and tolerability of this drug in usual clinical practice we performed the ELYPSE trial. Grade 1 or 2 essential hypertensive patients in whom their physicians considered to prescribe a dihydropyridine were conferred to Lercanidipine 10 mg once daily with a 3-month follow-up; 9059 patients were included (age: 63 +/- 11 years; 58% women, 60% over 60 years, 56% grade 2 hypertensives and 69% previously treated with other antihypertensive drugs). A subgroup of 1267 patients (14%) who were included in the study had experienced adverse reactions with other drugs. Electronic case-report forms and a central database (Internet) were used in this trial. At baseline, blood pressure (BP) was 160.1 +/- 10.2/95.6 +/- 6.6 mmHg; and heart rate (HR) 77.3 +/- 9.3 beats/min. Significant reductions in both systolic and diastolic BP were attained at 1 month with slight additional decreases 2 months later. At 3 months, BP was 141.4 +/- 11.3/ 83.1 +/- 6.9 mmHg, and HR 75.2 +/- 8.2 beats/min (p < 0.001 versus baseline). At the study end. 64% of the patients achieved a diastolic BP < 90 mmHg, BP control (< 140/90 mmHg) was attained in 32%. In the subgroup of diabetics (n = 1269) an adequate BP control (< 130/85) was attained in only 16.4%. The overall incidence of adverse events was 6.5%, of which the most frequent were headache (2.9%), ankle oedema (1.2%), flushing (1.1%) and palpitations (0.6%). Withdrawal rate was < 1%. The efficacy and tolerability in the subgroup of patients included in the study due to adverse events with other drugs were similar to the whole study group. In this study Lercanidipine has shown a good efficacy and tolerability in daily clinical practice. These findings are concordant with those reported in randomized controlled trials.

Antihypertensive effects of peroxisome proliferator-activated receptor-β/δ activation.

PubMed

Toral, Marta; Romero, Miguel; Pérez-Vizcaíno, Francisco; Duarte, Juan; Jiménez, Rosario

2017-02-01

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors, which is composed of three members encoded by distinct genes: PPARα, PPARβ/δ, and PPARγ. The biological actions of PPARα and PPARγ and their potential as a cardiovascular therapeutic target have been extensively reviewed, whereas the biological actions of PPARβ/δ and its effectiveness as a therapeutic target in the treatment of hypertension remain less investigated. Preclinical studies suggest that pharmacological PPARβ/δ activation induces antihypertensive effects in direct [spontaneously hypertensive rat (SHR), ANG II, and DOCA-salt] and indirect (dyslipemic and gestational) models of hypertension, associated with end-organ damage protection. This review summarizes mechanistic insights into the antihypertensive effects of PPARβ/δ activators, including molecular and functional mechanisms. Pharmacological PPARβ/δ activation induces genomic actions including the increase of regulators of G protein-coupled signaling (RGS), acute nongenomic vasodilator effects, as well as the ability to improve the endothelial dysfunction, reduce vascular inflammation, vasoconstrictor responses, and sympathetic outflow from central nervous system. Evidence from clinical trials is also examined. These preclinical and clinical outcomes of PPARβ/δ ligands may provide a basis for the development of therapies in combating hypertension. Copyright © 2017 the American Physiological Society.

Diuretic use is associated with better learning and memory in older adults in the Ginkgo Evaluation of Memory Study.

PubMed

Yasar, Sevil; Lin, Fu-Mei; Fried, Linda P; Kawas, Claudia H; Sink, Kaycee M; DeKosky, Steven T; Carlson, Michelle C

2012-05-01

To investigate the association between diuretics, angiotensin-converting enzyme inhibitors (ACE-I), angiotensin II receptor blockers (AT2RB), and cognitive function. This post hoc analysis of the randomized controlled Ginkgo Evaluation of Memory Study trial focuses on 3069 nondemented community-dwelling participants aged >75 years. At baseline visit, detailed information about medication use was collected and five cognitive domains were assessed. Multivariate linear regression analyses were used to assess cross-sectional associations between medication use and cognitive function. In all, 36% of participants reported history of hypertension and 53% reported antihypertensive medication use, with 17% reporting diuretic, 11% ACE-I, and 2% AT2RB use. Potassium-sparing diuretic use (N = 192) was associated with better verbal learning and memory measured by California Verbal Learning Test as compared with no antihypertensive medication users (β = 0.068, P = .01; β = 0.094, P < .001) and other antihypertensive medication users (β = 0.080, P = .03; β = 0.153, P < .001). Use of ACE-I or AT2RB was not associated with better cognitive function. Results warrant further investigation into possible protective effects of potassium-sparing diuretics and the role of potassium in mitigating cognitive decline. Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Interventional procedures and future drug therapy for hypertension.

PubMed

Lobo, Melvin D; Sobotka, Paul A; Pathak, Atul

2017-04-14

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Azilsartan and chlorthalidone -new powerful fixed dose antihypertensive combination.

PubMed

Katsi, Vasiliki; Athanasiadi, Eleni; Tsioufis, Costas; Tousoulis, Dimitris

2018-04-20

Arterial hypertension is a disease that still affects a major part of the population worldwide, and leads to fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. From the CDC statistical analysis, as regarding to United States, 1 of every 3 adults has high blood pressure, and οnly about half (54%) of them have it under control. Furthermore, all that leads to a nation cost about $46 billion each year. Efforts to find new ways to regulate arterial hypertension are therefore imperative. In our days, a lot of reference has been made to the use of a new therapeutic combination, that of azilsartan - an innovative ARB, in combination with chlorthalidone. Ιn fact, it is a combination now prescribed in a number of countries. A significant number of trials shows both azilsartan vs popular antihypertensive drugs, as well as chlorthalidone vs chlorothiazide, to present a better antihypertensive effect. This effect is even greater when the two substances are combined. In this article we will try to present the latest findings concerning the efficacy, safety and clinical utility of this combination, as well as its adverse events, in comparison with other widely used therapeutic options. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Omega-3 polyunsaturated fatty acids for the prevention of cardiovascular disease: do formulation, dosage & comparator matter?

PubMed

DiNicolantonio, James J; Meier, Pascal; O'Keefe, James H

2013-01-01

Multiple trials over the past two decades testing omega-3 polyunsaturated fatty acids (PUFAs), containing eicosapentaenoic acid (EPA) and or docosahexaenoic acid (DHA), have shown substantial benefits for reducing major coronary heart disease (CHD) events, all-cause mortality, cardiovascular (CV) death, sudden cardiac death (SCD), and stroke. However, recent trials testing omega-3s have generally failed to confirm these benefits. While increased fish and fish oil intake among the general population, increased use of optimal medical therapy (including statins, aspirin, and modern antihypertensive medications) probably make it more challenging for fish oil supplementation to show additional benefits, there might be further explanations in the formulation, dosage, and comparator used in these recent omega-3 trials.

Acute and chronic effects of aerobic exercise on blood pressure in resistant hypertension: study protocol for a randomized controlled trial.

PubMed

Nascimento, L S; Santos, A C; Lucena, Jms; Silva, Lgo; Almeida, Aem; Brasileiro-Santos, M S

2017-06-02

Resistant hypertension is a specific condition that affects approximately 10% of subjects with hypertension, and is characterized by persistently high blood pressure levels even using therapy of three or more antihypertensive agents or with blood pressure control using therapy with four or more antihypertensive agents. Changes in lifestyle, such as physical exercise, are indicated for controlling blood pressure. However, investigating studies about this therapy in individuals with resistant hypertension are few. This is a randomized controlled clinical trial. Forty-eight patients with resistant hypertension will be submitted to perform four short-term interventions: aerobic exercise sessions (mild-, moderate- and high-intensity) and control session, in random order and on separate days. After the short-term sessions, the patients will be randomly allocated into four groups for 8 weeks of follow-up: mild-, moderate- and high-intensity aerobic exercise, and a control group. The primary outcome is the occurrence of blood pressure reduction (office and ambulatory analysis, and acute and chronic effects). Secondary outcomes are autonomic and hemodynamic mechanisms: cardiac and vasomotor autonomic modulation, spontaneous baroreflex sensitivity, forearm blood flow and vascular resistance. The importance of exercise for hypertension has been known for decades, but little is known about the effects on patients with resistant hypertension. This study will help to understand whether different aerobic exercise intensities can induce different responses, as well as by what mechanisms adjustments in blood pressure levels may occur. ClinicalTrials.gov, ID: NCT02670681 . Registered on 28 January 2016 (first version); Brazilian Registry Platform Clinical Trials: protocol RBR-5q24zh . Registered on 24 June 2015.

The management and treatment of hypertension.

PubMed

Germino, F Wilford

2009-01-01

High blood pressure (HBP) is one of the most prevalent conditions seen today by clinicians, affecting an estimated 73 million--or 1 in 3--adult Americans, only one third of whom have achieved control of their hypertension (HBP). Central to the management of this pervasive medical condition are the issues of accurate diagnosis and maintaining control through appropriate treatment. Accurate diagnosis depends primarily on reliable measurement. Over the years, it has become increasingly recognized that blood pressure (BP) measurement occurring in clinical settings produces far less accurate and reliable readings than do other methods, notably 24-hour ambulatory BP monitoring and home BP measurement. Beyond technique, there are additional challenges to obtaining accurate readings, including emotional factors that produce either falsely elevated or lowered results, having the potential to mislead the clinician. The need to overcome obstacles to proper diagnosis and determine effective treatments has reached heightened urgency, especially for patients with compelling comorbidities such as diabetes, renal disease, congestive heart failure, and other cardiovascular diseases. The continuing evolution of the management of HBP is reflected in updated guidelines from the American Heart Association and evidence-based information stemming from recent studies and randomized clinical trials. The appropriate selection of antihypertensive agents, at the proper doses, is a complex issue requiring greater understanding of our pharmacologic options. The contributions of some of the more recent and salient studies and trials are mentioned here, although there is no attempt in this brief review to match drug classes with compelling indications. The trials discussed involve such pharmacologic treatments as diuretic therapy, alpha-blockers, conventional beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Trial outcomes shed light on the relative benefits and drawbacks of these agents, often within the context of various patient characteristics such as age, comorbidities, and risk status. Successful management of HBP is a multi-faceted and ongoing endeavor, in which developing knowledge constantly tempered by new questions moves us toward the goal of improving the lives of our patients.

Medication adherence in randomized controlled trials evaluating cardiovascular or mortality outcomes in dialysis patients: A systematic review.

PubMed

Murali, Karumathil M; Mullan, Judy; Chen, Jenny H C; Roodenrys, Steven; Lonergan, Maureen

2017-01-31

Medication non-adherence is common among renal dialysis patients. High degrees of non-adherence in randomized controlled trials (RCTs) can lead to failure to detect a true treatment effect. Cardio-protective pharmacological interventions have shown no consistent benefit in RCTs involving dialysis patients. Whether non-adherence contributes to this lack of efficacy is unknown. We aimed to investigate how medication adherence and drug discontinuation were assessed, reported and addressed in RCTs, evaluating cardiovascular or mortality outcomes in dialysis patients. Electronic database searches were performed in MEDLINE, EMBASE & Cochrane CENTRAL for RCTs published between 2005-2015, evaluating self-administered medications, in adult dialysis patients, which reported clinical cardiovascular or mortality endpoints, as primary or secondary outcomes. Study characteristics, outcomes, methods of measuring and reporting adherence, and data on study drug discontinuation were analyzed. Of the 642 RCTs in dialysis patients, 22 trials (12 placebo controlled), which included 19,322 patients, were eligible. The trialed pharmacological interventions included anti-hypertensives, phosphate binders, lipid-lowering therapy, cardio-vascular medications, homocysteine lowering therapy, fish oil and calcimimetics. Medication adherence was reported in five trials with a mean of 81% (range: 65-92%) in the intervention arm and 84.5% (range: 82-87%) in the control arm. All the trials that reported adherence yielded negative study outcomes for the intervention. Study-drug discontinuation was reported in 21 trials (mean 33.2%; 95% CI, 22.0 to 44.5, in intervention and 28.8%; 95% CI, 16.8 to 40.8, in control). Trials with more than 20% study drug discontinuation, more often yielded negative study outcomes (p = 0.018). Non-adherence was included as a contributor to drug discontinuation in some studies, but the causes of discontinuation were not reported consistently between studies, and non-adherence was listed under different categories, thereby potentiating the misclassification of adherence. Reporting of medication adherence and study-drug discontinuation in RCTs investigating cardiovascular or mortality endpoints in dialysis patients are inconsistent, making it difficult to compare studies and evaluate their impact on outcomes. Recommendations for consistent reporting of non-adherence and causes of drug discontinuation in RCTs will therefore help to assess their impact on clinical outcomes.

Hypertension and Heart Failure with Preserved Ejection Fraction: Connecting the Dots.

PubMed

Tsioufis, Costas; Georgiopoulos, Georgios; Oikonomou, Dimitrios; Thomopoulos, Costas; Katsiki, Niki; Kasiakogias, Alexandros; Chrysochoou, Christina; Konstantinidis, Dimitrios; Kalos, Theodoros; Tousoulis, Dimitrios

2017-01-01

Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for approximately 50% of HF cases and its prevalence relative to HF with reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF patients and it is implicated in both the pathogenesis and the prognosis of the disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We reviewed the literature for epidemiologic data supporting the co-aggregation of the two entities as well as patho-physiologic mechanisms linking HT to HFpEF. Most importantly, we focused on treatment options targeting HT as a preventive strategy for delaying the progression of diastolic dysfunction or decreasing the odds for developing HFpEF. Along this line, we summarized the evidence and efficacy associated with different classes of antihypertensive medications in HFpEF patients. Finally, non-pharmacological approaches, including renal denervation and lifestyle modifications, to achieve optimal blood pressure (BP) control in HFpEF patients are reported. Unfortunately, no specific antihypertensive treatment has established a major survival benefit in this high risk subjects. Until the results of the efficacy of the novel drug LCZ696 (valsartan/ sacubitril) are available, the continuous monitoring and lowering of the BP by pharmacological and non-pharmacological means should be considered the major preventive and treatment strategy in HFpEF patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Oral potassium supplementation for management of essential hypertension: A meta-analysis of randomized controlled trials

PubMed Central

Zeraati, Fatemeh; Soltanian, Ali Reza; Sheikh, Vida; Hooshmand, Elham; Maleki, Akram

2017-01-01

Importance Increased dietary potassium intake is thought to be associated with low blood pressure (BP). Whether potassium supplementation may be used as an antihypertensive agent is a question that should be answered. Objective To assess the effect of oral potassium supplementation on blood pressure in patients with primary hypertension. Search methods We searched Medline, Web of Science, Scopus, Cochrane Central Register of Controlled Trials until October 2016. We also screened reference lists of articles and previous reviews. We applied no language restrictions. Selection criteria We included randomized placebo-controlled clinical trials addressing the effect of potassium supplementation on primary hypertension for a minimum of 4 weeks. Data collection and analysis We extracted data on systolic and diastolic BP (SBP and DBP) at the final follow-up. We explored the heterogeneity across studies using Cochran's test and I2 statistic and assessed the probability of publication bias using Begg's and Egger's tests. We reported the mean difference (MD) of SBP and DBP in a random-effects model. Results We found a total of 9059 articles and included 23 trials with 1213 participants. Compared to placebo, potassium supplementation resulted in modest but significant reductions in both SBP (MD -4.25 mmHg; 95% CI: -5.96 to -2.53; I2 = 41%) and DBP (MD -2.53 mmHg; 95% CI: -4.05 to -1.02; I2 = 65%). According to the change-score analysis, based on 8 out of 23 trials, compared to baseline, the mean changes in SBP (MD -8.89 mmHg; 95% CI: -13.67 to -4.11) and DBP (MD -6.42 mmHg; 95% CI: -10.99 to -1.84) was significantly higher in the intervention group than the control group. Conclusions Our findings indicated that potassium supplementation is a safe medication with no important adverse effects that has a modest but significant impact BP and may be recommended as an adjuvant antihypertensive agent for patients with essential hypertension. PMID:28419159

Geographic differences in heart failure trials.

PubMed

Ferreira, João Pedro; Girerd, Nicolas; Rossignol, Patrick; Zannad, Faiez

2015-09-01

Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial-specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF-PEF), heart failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF-PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

[How to Increase the Effectiveness of Antihypertensive Therapy in Clinical Practice: Results of the Russian Observational Program FORSAZH].

PubMed

Glezer, M G; Deev On Behalf Of The Participants Of The Program, A D

2016-01-01

im of the study - to evaluate the possibility of increasing the effectiveness of antihypertensive therapy by simplifying regimens, improving knowledge and practical skills of the doctors on the use of modern tactical approaches to treatment as well as patients education methods of measuring blood pressure (BP), the principles of a healthy lifestyle and explain the need to follow the prescribing physician. Post-marketing observational discovery program FORSAZH held in 29 cities of the Russian Federation. Participation in the program received 442 physician (internists and general practitioners), which included 1969 patients with prior failure of combination antihypertensive therapy. Patients in 86% of cases took the free combination, 14% - fixed combinations of drugs. The change of the treatment on reception of a preparation containing a fixed combination of perindopril/indapamide (10 mg/2.5 mg) after 3 months led to decrease in systolic blood pressure by an average of 39.5 mm Hg, diastolic - 18.7 per mm Hg. The frequency of achieving the target BP <140 mm Hg and 90 it was 76%. Marked reduction in BP and frequency to achieve the target BP is not dependent on additional training of physicians and patients, the use of prior therapy in free or fixed combination, but depended on the initial degree of increase in BP and duration of therapy. Predictors of failure to achieve target BP were age, male gender, low initial adherence, good health, a higher baseline BP, elevated cholesterol levels, body weight, heart rate and decreased glomerular filtration rate. Adherence to therapy patients (on a scale of Morisky-Green) and health assessment on a visual analog scale significantly increased. This tactic has been a change of therapy is not only effective but also safe. Adverse events were reported in 28 patients (1.4% of the total number of observed cases) and only 1 case required dose reduction due to development of clinically manifested hypotension. In enhancing the effectiveness of the treatment of patients with hypertension was decisive simplification of drug therapy through the use of a fixed combination of perindopril A/indapamide.

Blood pressure reduction and antihypertensive medication use in the losartan intervention for endpoint reduction in hypertension (LIFE) study in patients with hypertension and left ventricular hypertrophy.

PubMed

Devereux, Richard B; de Faire, Ulf; Fyhrquist, Frej; Harris, Katherine E; Ibsen, Hans; Kjeldsen, Sverre E; Lederballe-Pedersen, Ole; Lindholm, Lars H; Nieminen, Markku S; Omvik, Per; Oparil, Suzanne; Wedel, Hans; Hille, Darcy A; Dahlöf, Björn

2007-02-01

To compare blood pressure response and antihypertensive medication use visit-by-visit from baseline in patients receiving losartan-based or atenolol-based therapy in the LIFE study. LIFE was a randomized, double-blind trial comparing losartan-based and atenolol-based treatment regimens on the primary composite endpoint of death, myocardial infarction (MI), or stroke in 9193 patients aged 55-80 years with hypertension and left ventricular hypertrophy. Systolic and diastolic, pulse, and mean arterial pressures, blood pressure responder rates, distribution of open-label antihypertensive agents utilized, and the proportion of patients on randomized treatment were determined for each group at each clinic visit over a follow-up period of at least 4 years. Overall blood pressure reductions were comparable in the losartan-based and atenolol-based treatment groups. The mean reductions in sitting trough systolic and diastolic blood pressures from baseline to the end of follow-up (or last visit before a primary endpoint event) were 30.2/16.6 mmHg in the losartan group and 29.1/16.8 mmHg in the atenolol group. The time-averaged difference in overall mean arterial pressure was similar between groups. The proportion of patients on individual dose combinations varied visit by visit but was generally comparable between groups. During the entire study, 56% (2579/4605) of losartan-treated patients received at least one dose of the combination of losartan 100 mg plus hydrochlorothiazide 12.5 mg and 51% of atenolol-treated patients received 100 mg of atenolol plus hydrochlorothiazide 12.5 mg at some time during the study. Differences in blood pressure or distribution of add-on medications between treatment groups were not evident in the LIFE trial and, thus, cannot account for the observed outcome difference in the primary endpoint of risk reduction of the composite of cardiovascular death, stroke and MI favoring losartan.

Treatment of essential hypertension with calcium channel blockers: what is the place of lercanidipine?

PubMed

Burnier, Michel; Pruijm, Menno; Wuerzner, Gregoire

2009-08-01

In all actual clinical guidelines, dihydropyridine calcium channel blockers (CCBs) belong to the recommended first line antihypertensive drugs to treat essential hypertension. Several recent large clinical trials have confirmed their efficacy not only in lowering blood pressure but also in reducing cardiovascular morbidity and mortality in hypertensive patients with a normal or high cardiovascular risk profile. In clinical trials such as ALLHAT, VALUE or ASCOT, an amlodipine-based therapy was at least as effective, when not slightly superior, in lowering blood pressure and sometimes more effective in preventing target organ damages than blood pressure lowering strategies based on the use of diuretics, beta-blockers and blockers of the renin-angiotensin system. One of the main clinical side effects of the first and second generation CCBs including amlodipine is the development of peripheral edema. The incidence of leg edema can be markedly reduced by combining the CCB with a blocker of the renin-angiotensin system. This strategy has now led to the development of several fixed-dose combinations of amlodipine and angiotensin II receptor antagonists. Another alternative to lower the incidence of edema is to use CCBs of the third generation such as lercanidipine. Indeed, although no major clinical trials have been conducted with this compound, clinical studies have shown that lercanidipine and amlodipine have a comparable antihypertensive efficacy but with significantly less peripheral edema in patients receiving lercanidipine. In some countries, lercanidipine is now available in a single-pill association with an ACE inhibitor thereby further improving its efficacy and tolerability profile.

Azilsartan medoxomil/chlorthalidone: a new fixed-dose combination antihypertensive.

PubMed

Pierini, Danielle; Anderson, Katherine Vogel

2013-05-01

To evaluate the efficacy, safety, and clinical utility of the combination product azilsartan medoxomil/chlorthalidone for the treatment of hypertension. Articles indexed in PubMed through December 2012 were identified using the MeSH terms azilsartan and chlorthalidone, Edarbyclor, TAK-490, and Edarbi. Additional information was gathered from references cited in the identified publications, the package insert, and from a review of the ClinicalTrials.gov registry. English-language articles, including clinical trials and reviews involving azilsartan medoxomil/chlorthalidone or each component individually for the treatment of hypertension were reviewed. The antihypertensive combination tablet azilsartan medoxomil/chlorthalidone is the first to combine an inhibitor of the renin-angiotensin-aldosterone system with chlorthalidone, a thiazide-type diuretic. In 4 randomized controlled trials (3 published to date), azilsartan medoxomil/chlorthalidone 40 mg/12.5 mg and 40 mg/25 mg reduced blood pressure (BP) significantly more than comparators did, including an approximately 5-mm Hg greater BP reduction than olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg and azilsartan medoxomil/hydrochlorothiazide. Reductions in 24-hour ambulatory BP and clinic BP were observed, and a greater proportion of patients achieved BP targets while receiving azilsartan medoxomil/chlorthalidone. Azilsartan medoxomil/chlorthalidone was generally well tolerated, with minor, transient increases in serum creatinine and without a significant effect on potassium homeostasis. No studies have directly examined cardiovascular morbidity and mortality benefits associated with this combination. The combination of azilsartan medoxomil/chlorthalidone has demonstrated safety and efficacy in lowering BP in hypertensive patients to a greater degree than olmesartan medoxomil/hydrochlorothiazide and azilsartan medoxomil/hydrochlorothiazide. As a fixed-dose combination tablet, it offers several clinical advantages.

Recurrent syncope, orthostatic hypotension and volatile hypertension: think outside the box.

PubMed

Aung, Thein; Fan, Wuqiang; Krishnamurthy, Mahesh

2013-01-01

The baroreceptors in the neck and aortic arch are important regulators of sudden blood pressure changes. They are innervated by CN IX and X and synapse in the brainstem. Baroreceptor failure is an under-recognized cause of recurrent syncope, orthostatic hypotension, and volatile hypertension, which is refractory to and may in fact worsen with conventional treatments. Baroreflex failure can be the result of neck and chest radiation, head and neck surgery, and cerebrovascular accidents involving the brainstem nuclei. The management of baroreflex failure is a challenge since patient education, lifestyle changes, and family support are extremely important in managing blood pressure. Leg exercises and Thrombo-Embolic Deterrent Stockings (TED) stockings are important in treating orthostatic hypotension. Clonidine is the antihypertensive of choice for supine hypertension. Low-dose benzodiazepines are helpful in suppressing sympathetic surges. We have encountered two patients with baroreflex failure after chemotherapy and radiation to the neck or upper chest. Temporal relationship between symptoms onset and the history of head, neck, and upper chest radiation or trauma is important in reaching a diagnosis.

Mobile applications for handheld devices to screen and randomize acute stroke patients in clinical trials.

PubMed

Qureshi, Ai; Connelly, B; Abbott, Ei; Maland, E; Kim, J; Blake, J

2012-08-01

The availability of internet connectivity and mobile application software used by low-power handheld devices makes smart phones of unique value in time-sensitive clinical trials. Trial-specific applications can be downloaded by investigators from various mobile software distribution platforms or web applications delivered over HTTP. The Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH) II investigators in collaboration with MentorMate released the ATACH-II Patient Recruitment mobile application available on iPhone, Android, and Blackberry in 2011. The mobile application provides tools for pre-screening, assessment of eligibility, and randomization of patients. Since the release of ATACH-II mobile application, the CLEAR-IVH (Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage) trial investigators have also adopted such a mobile application. The video-conferencing capabilities of the most recent mobile devices open up additional opportunities to involve central coordinating centers in the recruitment process in real time.

Improving blood pressure control in diabetes: limitations of a clinical reminder in influencing physician behavior.

PubMed

Sanders, Karen M; Satyvavolu, Anuradha

2002-01-01

Hypertension should be aggressively treated, especially in diabetic patients. But studies of physician prescribing habits reveal that physicians often delay making medication changes or initiating antihypertensive therapy. A chart-based reminder was designed to improve physician medication prescribing in this clinical situation. A randomized controlled trial was conducted at the Veterans Affairs Medical Center in Richmond, Virginia. Patients with diabetes and hypertension were selected. A highly visible chart reminder was applied to the front of outpatient charts in the intervention group practice. A chart review was conducted to assess physician-directed medication changes. A successful outcome was defined as any antihypertensive medication increase or addition at that same visit. Physicians were more likely to intensify antihypertensive medication as the blood pressure increased regardless of the reminder. Overall, only 33% of visits resulted in a medication change, even though 93% of patients had elevations over target blood pressure at the follow-up visit. Physicians in the intervention and control groups made changes to medication at similar rates (chi 2 = 0.621, p = .511). In this study, a chart reminder failed to improve physician compliance with the clinical guideline for hypertension management in diabetics, Sixth Report of the Joint National Committee on the Detection, Evaluation, Prevention and Treatment of High Blood Pressure. To inform the design of effective intervention strategies, further research should explore specific barriers to guideline adherence in this clinical situation.

Differential role of afferent and efferent renal nerves in the maintenance of early- and late-phase Dahl S hypertension

PubMed Central

Foss, Jason D.; Fink, Gregory D.

2015-01-01

Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect is due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats to a similar degree observed in clinical trials. In addition, we have recently developed a method for selective ablation of afferent renal nerves (renal-CAP). In the present study, we tested the hypothesis that the antihypertensive effect of RDNX in the Dahl S rat is due to ablation of afferent renal nerves by comparing the effect of complete RDNX to renal-CAP during two phases of hypertension in the Dahl S rat. In the early phase, rats underwent treatment after 3 wk of high-NaCl feeding when mean arterial pressure (MAP) was ∼140 mmHg. In the late phase, rats underwent treatment after 9 wk of high NaCl feeding, when MAP was ∼170 mmHg. RDNX reduced MAP ∼10 mmHg compared with sham surgery in both the early and late phase, whereas renal-CAP had no antihypertensive effect. These results suggest that, in the Dahl S rat, the antihypertensive effect of RDNX is not dependent on pretreatment arterial pressure, nor is it due to ablation of afferent renal nerves. PMID:26661098

Failure mode and effects analysis drastically reduced potential risks in clinical trial conduct.

PubMed

Lee, Howard; Lee, Heechan; Baik, Jungmi; Kim, Hyunjung; Kim, Rachel

2017-01-01

Failure mode and effects analysis (FMEA) is a risk management tool to proactively identify and assess the causes and effects of potential failures in a system, thereby preventing them from happening. The objective of this study was to evaluate effectiveness of FMEA applied to an academic clinical trial center in a tertiary care setting. A multidisciplinary FMEA focus group at the Seoul National University Hospital Clinical Trials Center selected 6 core clinical trial processes, for which potential failure modes were identified and their risk priority number (RPN) was assessed. Remedial action plans for high-risk failure modes (RPN >160) were devised and a follow-up RPN scoring was conducted a year later. A total of 114 failure modes were identified with an RPN score ranging 3-378, which was mainly driven by the severity score. Fourteen failure modes were of high risk, 11 of which were addressed by remedial actions. Rescoring showed a dramatic improvement attributed to reduction in the occurrence and detection scores by >3 and >2 points, respectively. FMEA is a powerful tool to improve quality in clinical trials. The Seoul National University Hospital Clinical Trials Center is expanding its FMEA capability to other core clinical trial processes.

Diuretics in the treatment of hypertension. Part 2: loop diuretics and potassium-sparing agents.

PubMed

Tamargo, Juan; Segura, Julian; Ruilope, Luis M

2014-04-01

Diuretics enhance the renal excretion of Na(+) and water due to a direct action at different tubular sites of the nephron where solute re-absorption occurs. This paper focuses on the mechanism of action, pharmacodynamics, antihypertensive effects, adverse effects, interactions and contraindications of loop diuretics and potassium-sparing agents (including mineralocorticoid receptor antagonists (MRAs) and epithelial Na(+) channel blockers). Loop diuretics are less effective than thiazide diuretics in lowering blood pressure, so that their major use is in edematous patients with congestive heart failure (HF), cirrhosis with ascites and nephritic edema. MRAs represent a major advance in the treatment of resistant hypertension, primary and secondary hyperaldosteronism and in patients with systolic HF to reduce the risks of hospitalization and of premature death. Potassium-sparing diuretics when coadministered with diuretics (thiazides and loop diuretics) working at more proximal nephron locations reduce the risk of hypokalemia and hypomagnesemia and the risk of cardiac arrhythmias. At the end of the article, the basis for the combination of diuretics with other antihypertensive drugs to achieve blood pressure targets is presented.

[Adherence to anti-hypertensive treatment within a chronic disease management 
program: a longitudinal, retrospective study].

PubMed

Raymundo, Ana Carolina Nascimento; Pierin, Angela Maria Geraldo

2014-10-01

This study assessed pharmacological treatment adherence using the Morisky-Green Test and identified related variables. A longitudinal and retrospective study examined 283 patients with hypertension (62.5% women, 73.4 [10.9] years old) who were being monitored by a chronic disease management program for 17 months between 2011 and 2012. Nurses performed all the actions of the program, which consisted of advice via telephone and periodic home visits based on the risk stratification of the patients. A significant increase in treatment adherence (25.1% vs. 85.5%) and a decrease in blood pressure were observed (p<0.05). Patients with hypertension and chronic renal failure as well as those treated using angiotensin-converting enzyme inhibitors were the most adherent (p<0.05). Patients with hypertension who received angiotensin receptor blockers were less adherent (p<0.05). Strategies such as nurse-performed chronic disease management can increase adherence to anti-hypertensive treatment and therefore contribute to the control of blood pressure, minimizing the morbidity profiles of patients with hypertension.

Confident failures: Lapses of working memory reveal a metacognitive blind spot.

PubMed

Adam, Kirsten C S; Vogel, Edward K

2017-07-01

Working memory performance fluctuates dramatically from trial to trial. On many trials, performance is no better than chance. Here, we assessed participants' awareness of working memory failures. We used a whole-report visual working memory task to quantify both trial-by-trial performance and trial-by-trial subjective ratings of inattention to the task. In Experiment 1 (N = 41), participants were probed for task-unrelated thoughts immediately following 20% of trials. In Experiment 2 (N = 30), participants gave a rating of their attentional state following 25% of trials. Finally, in Experiments 3a (N = 44) and 3b (N = 34), participants reported confidence of every response using a simple mouse-click judgment. Attention-state ratings and off-task thoughts predicted the number of items correctly identified on each trial, replicating previous findings that subjective measures of attention state predict working memory performance. However, participants correctly identified failures on only around 28% of failure trials. Across experiments, participants' metacognitive judgments reliably predicted variation in working memory performance but consistently and severely underestimated the extent of failures. Further, individual differences in metacognitive accuracy correlated with overall working memory performance, suggesting that metacognitive monitoring may be key to working memory success.

The Cost-Effectiveness of Low-Cost Essential Antihypertensive Medicines for Hypertension Control in China: A Modelling Study.

PubMed

Gu, Dongfeng; He, Jiang; Coxson, Pamela G; Rasmussen, Petra W; Huang, Chen; Thanataveerat, Anusorn; Tzong, Keane Y; Xiong, Juyang; Wang, Miao; Zhao, Dong; Goldman, Lee; Moran, Andrew E

2015-08-01

Hypertension is China's leading cardiovascular disease risk factor. Improved hypertension control in China would result in result in enormous health gains in the world's largest population. A computer simulation model projected the cost-effectiveness of hypertension treatment in Chinese adults, assuming a range of essential medicines list drug costs. The Cardiovascular Disease Policy Model-China, a Markov-style computer simulation model, simulated hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring costs, disease-related costs, and quality-adjusted life years (QALYs) gained by preventing cardiovascular disease or lost because of drug side effects in untreated hypertensive adults aged 35-84 y over 2015-2025. Cost-effectiveness was assessed in cardiovascular disease patients (secondary prevention) and for two blood pressure ranges in primary prevention (stage one, 140-159/90-99 mm Hg; stage two, ≥160/≥100 mm Hg). Treatment of isolated systolic hypertension and combined systolic and diastolic hypertension were modeled as a reduction in systolic blood pressure; treatment of isolated diastolic hypertension was modeled as a reduction in diastolic blood pressure. One-way and probabilistic sensitivity analyses explored ranges of antihypertensive drug effectiveness and costs, monitoring frequency, medication adherence, side effect severity, background hypertension prevalence, antihypertensive medication treatment, case fatality, incidence and prevalence, and cardiovascular disease treatment costs. Median antihypertensive costs from Shanghai and Yunnan province were entered into the model in order to estimate the effects of very low and high drug prices. Incremental cost-effectiveness ratios less than the per capita gross domestic product of China (11,900 international dollars [Int$] in 2015) were considered cost-effective. Treating hypertensive adults with prior cardiovascular disease for secondary prevention was projected to be cost saving in the main simulation and 100% of probabilistic simulation results. Treating all hypertension for primary and secondary prevention would prevent about 800,000 cardiovascular disease events annually (95% uncertainty interval, 0.6 to 1.0 million) and was borderline cost-effective incremental to treating only cardiovascular disease and stage two patients (2015 Int$13,000 per QALY gained [95% uncertainty interval, Int$10,000 to Int$18,000]). Of all one-way sensitivity analyses, assuming adherence to taking medications as low as 25%, high Shanghai drug costs, or low medication efficacy led to the most unfavorable results (treating all hypertension, about Int$47,000, Int$37,000, and Int$27,000 per QALY were gained, respectively). The strengths of this study were the use of a recent Chinese national health survey, vital statistics, health care costs, and cohort study outcomes data as model inputs and reliance on clinical-trial-based estimates of coronary heart disease and stroke risk reduction due to antihypertensive medication treatment. The limitations of the study were the use of several sources of data, limited clinical trial evidence for medication effectiveness and harms in the youngest and oldest age groups, lack of information about geographic and ethnic subgroups, lack of specific information about indirect costs borne by patients, and uncertainty about the future epidemiology of cardiovascular diseases in China. Expanded hypertension treatment has the potential to prevent about 800,000 cardiovascular disease events annually and be borderline cost-effective in China, provided low-cost essential antihypertensive medicines programs can be implemented.

Home and Online Management and Evaluation of Blood Pressure (HOME BP) digital intervention for self-management of uncontrolled, essential hypertension: a protocol for the randomised controlled HOME BP trial

PubMed Central

Morton, Katherine; Stuart, Beth; Raftery, James; Bradbury, Katherine; Yao, Guiqing Lily; Zhu, Shihua; Little, Paul; Yardley, Lucy

2016-01-01

Introduction Self-management of hypertension, including self-monitoring and antihypertensive medication titration, lowers blood pressure (BP) at 1 year compared to usual care. The aim of the current trial is to assess the effectiveness of the Home and Online Management and Evaluation of Blood Pressure (HOME BP) intervention for the self-management of hypertension in primary care. Methods and analysis The HOME BP trial will be a randomised controlled trial comparing BP self-management—consisting of the HOME BP online digital intervention with self-monitoring, lifestyle advice and antihypertensive drug titration—with usual care for people with uncontrolled essential hypertension. Eligible patients will be recruited from primary care and randomised to usual care or to self-management using HOME BP. The primary outcome will be the difference in mean systolic BP (mm Hg) at 12-month follow-up between the intervention and control groups adjusting for baseline BP and covariates. Secondary outcomes (also adjusted for baseline and covariates where appropriate) will be differences in mean BP at 6 months and diastolic BP at 12 months; patient enablement; quality of life, and economic analyses including all key resources associated with the intervention and related services, adopting a broad societal perspective to include NHS, social care and patient costs, considered within trial and modelled with a lifetime horizon. Medication beliefs, adherence and changes; self-efficacy; perceived side effects and lifestyle changes will be measured for process analyses. Qualitative analyses will explore patient and healthcare professional experiences of HOME BP to gain insights into the factors affecting acceptability, feasibility and adherence. Ethics and dissemination This study has received NHS ethical approval (REC reference 15/SC/0082). The findings from HOME BP will be disseminated widely through peer-reviewed publications, scientific conferences and workshops. If successful, HOME BP will be directly applicable to UK primary care management of hypertension. Trial registration number ISRCTN13790648; pre-results. PMID:27821598

Mechanisms of epoxyeicosatrienoic acids to improve cardiac remodeling in chronic renal failure disease.

PubMed

Zhang, Kun; Wang, Ju; Zhang, Huanji; Chen, Jie; Zuo, Zhiyi; Wang, Jingfeng; Huang, Hui

2013-02-15

Both clinical and basic science studies have demonstrated that cardiac remodeling in patients with chronic renal failure (CRF) is very common. It is a key feature during the course of heart failure and an important risk factor for subsequent cardiac mortality. Traditional drugs or therapies rarely have effects on cardiac regression of CRF and cardiovascular events are still the first cause of death. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acids metabolized by cytochrome P450 epoxygenases. It has been found that EETs have important biological effects including anti-hypertension and anti-inflammation. Recent data suggest that EETs are involved in regulating cardiomyocyte injury, renal dysfunction, chronic kidney disease (CKD)-related risk factors and signaling pathways, all of which play key roles in cardiac remodeling induced by CRF. This review analyzes the literature to identify the possible mechanisms for EETs to improve cardiac remodeling induced by CRF and indicates the therapeutic potential of EETs in it. Copyright © 2012 Elsevier B.V. All rights reserved.

Should We STOP Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Advanced Kidney Disease?

PubMed

Ahmed, Aimun; Jorna, Tom; Bhandari, Sunil

2016-01-01

Chronic kidney disease (CKD) is a worldwide public health problem associated with a high prevalence of cardiovascular disease (CVD) and impaired quality of life. Previous research for preventing loss of glomerular filtration rate (GFR) has focused on reducing blood pressure (BP) and proteinuria. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor antagonists (ARB) are commonly used in patients with early CKD, but their value in advanced CKD (estimated GFR (eGFR) ≤30 ml/min/1.73 m2) is unknown. There remains a debate about the omission of ACEi/ARB in patients with advanced CKD and their use in association with CVD or heart failure. Does the potential gain in eGFR with ACEi/ARB cessation outweigh the potential adverse cardiovascular outcomes? This paper reviews the current literature that addresses this issue. Several controversies are discussed. Although lowering BP reduces cardiovascular events, evidence suggests that ACEi/ARBs are not superior to other antihypertensive agents. There are no studies assessing the benefits of ACEi/ARB therapy in cardiovascular risk reduction in advanced non-dialysis CKD. The STOP ACEi trial will strengthen the evidence base and shed light on the potential merits and dangers of ACEi/ARB use in advanced CKD on renal function and cardiovascular outcomes. © 2016 S. Karger AG, Basel.

The Divergent Cardiovascular Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Blockers in Adult Patients With Type 2 Diabetes Mellitus.

PubMed

Strauss, Martin H; Hall, Alistair S

2018-04-01

The renin angiotensin aldosterone system (RAAS) plays a central role in the pathophysiology of hypertension and vascular disease. Angiotensin-converting enzyme inhibitors (ACEi's) suppress angiotensin II (ANG II) concentrations, whereas angiotensin II type 1 (AT 1 ) receptor blockers (ARBs) block the binding of ANG II to AT 1 receptors. ACEi's and ARBs are both effective antihypertensive agents and produce similar risk reductions for stroke, a blood pressure-dependent phenomenon. ACEi's also reduce the risk for myocardial infarction (MI) and all-cause mortality in high-risk hypertensive patients as well as in people with diabetes, vascular disease and congestive heart failure. ARBs, in contrast, do not reduce the risk for MI or death in randomized clinical trials when assessed vs. placebo. Systematic reviews of ARBs that include meta-analyses or metaregression analyses confirm that ARBs lack the cardiovascular-protective effects of ACEi's. Practice guidelines, especially those for high-risk patients, such as those with diabetes mellitus, should reflect the evidence that ACEi's and ARBs have divergent cardiovascular effects: ACEi's reduce mortality, whereas ARBs do not. ACEi's should remain the preferred RAAS inhibitor for patients at high risk. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Resistant hypertension and hyperaldosteronism.

PubMed

Gonzaga, Carolina C; Calhoun, David A

2008-12-01

Resistant hypertension is defined as blood pressure that remains uncontrolled in spite of >or= 3 antihypertensive medications at effective doses, ideally including a diuretic. Although exact prevalence is unknown, clinical trials suggest that 20% to 30% of study participants are resistant. Hyperaldosteronism, obesity, refractory volume expansion, and obstructive sleep apnea are common findings in resistant hypertension patients. Multiple studies indicate that primary aldosteronism (PA) is common (approximately 20%) in patients with resistant hypertension. Screening for PA is recommended for most patients with resistant hypertension, ideally by measurement of 24-hour urinary aldosterone excretion, or by the plasma aldosterone/plasma renin activity ratio. Successful treatment of resistant hypertension is predicated on improvement of lifestyle factors; accurate diagnosis and treatment of secondary causes of hypertension; and use of effective multidrug regimens. A long-acting diuretic, specifically chlorthalidone, is recommended as part of the treatment regimen. Recent studies demonstrate that mineralocorticoid receptor antagonists provide substantial antihypertensive benefit when added to multidrug regimens, even in patients without demonstrable aldosterone excess.

EARLY Treatment with azilsartan compared to ACE-inhibitors in anti-hypertensive therapy--rationale and design of the EARLY hypertension registry.

PubMed

Gitt, Anselm K; Baumgart, Peter; Bramlage, Peter; Mahfoud, Felix; Potthoff, Sebastian A; Senges, Jochen; Schneider, Steffen; Buhck, Hartmut; Schmieder, Roland E

2013-07-02

Arterial hypertension is highly prevalent but poorly controlled. Blood pressure (BP) reduction substantially reduces cardiovascular morbidity and mortality. Recent randomized, double-blind clinical trials demonstrated that azilsartan medoxomil (AZM) is more effective in reducing BP than the ubiquitary ACE inhibitor ramipril. Therefore, we aimed to test whether these can be verified under clinical practice conditions. The "Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy" (EARLY) registry is a prospective, observational, national, multicenter registry with a follow-up of up to 12 months. It will include up to 5000 patients on AZM or ACE-inhibitor monotherapy in a ratio of 7 to 3. A subgroup of patients will undergo 24-hour BP monitoring. EARLY has two co-primary objectives: 1) Description of the safety profile of azilsartan and 2) achievement of BP targets based on recent national and international guidelines for patients treated with azilsartan in comparison to those treated with ACE-inhibitors. The most important secondary endpoints are the determination of persistence with treatment and the documentation of cardiovascular and renal events. Recruitment commenced in January 2012 and will be completed by February 2013. The data obtained will supplement previous results from randomized controlled trials to document the potential value of utilizing azilsartan medoxomil in comparison to ACE-inhibitor treatment for target BP achievement in clinical practice.

Failure mode and effects analysis drastically reduced potential risks in clinical trial conduct

PubMed Central

Baik, Jungmi; Kim, Hyunjung; Kim, Rachel

2017-01-01

Background Failure mode and effects analysis (FMEA) is a risk management tool to proactively identify and assess the causes and effects of potential failures in a system, thereby preventing them from happening. The objective of this study was to evaluate effectiveness of FMEA applied to an academic clinical trial center in a tertiary care setting. Methods A multidisciplinary FMEA focus group at the Seoul National University Hospital Clinical Trials Center selected 6 core clinical trial processes, for which potential failure modes were identified and their risk priority number (RPN) was assessed. Remedial action plans for high-risk failure modes (RPN >160) were devised and a follow-up RPN scoring was conducted a year later. Results A total of 114 failure modes were identified with an RPN score ranging 3–378, which was mainly driven by the severity score. Fourteen failure modes were of high risk, 11 of which were addressed by remedial actions. Rescoring showed a dramatic improvement attributed to reduction in the occurrence and detection scores by >3 and >2 points, respectively. Conclusions FMEA is a powerful tool to improve quality in clinical trials. The Seoul National University Hospital Clinical Trials Center is expanding its FMEA capability to other core clinical trial processes. PMID:29089745

Minoxidil-associated anorexia in an infant with refractory hypertension.

PubMed

Vesoulis, Zachary A; Attarian, Stephanie J; Zeller, Brandy; Cole, Francis Sessions

2014-12-01

Minoxidil is a potent antihypertensive used as an adjunctive agent in refractory hypertension. It exerts an antihypertensive effect through two mechanisms: selective arterial vasodilation by activation of potassium channels in the vascular smooth muscle and stimulation of carotid and aortic baroreceptors, leading to downstream release of renin and norepinephrine. Although frequently cited in reviews of antihypertensive agents, limited data about the use of minoxidil in neonates are available. We describe an infant girl, born at 35 weeks of gestation, who was diagnosed with idiopathic hypertension after extensive diagnostic evaluation. Adequate blood pressure control was not achieved with captopril, amlodipine, and clonidine. Oliguria secondary to captopril and rapid-onset congestive heart failure due to persistent hypertension led to the introduction of intravenous agents labetalol and nitroprusside. Although adequate blood pressure control was achieved, attempts to transition back to oral agents were unsuccessful, prompting the use of minoxidil as an alternative agent. Although good blood pressure control was achieved, the infant's oral intake plummeted from 210 to 63 ml/kg/day. The anorexia quickly resolved after stopping minoxidil, and she was discharged home at 5 months of age receiving propranolol, amlodipine, and doxazosin. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 10) between the patient's development of anorexia and minoxidil therapy. To our knowledge, there have been no previous reports of minoxidil-associated anorexia in preterm or term infants. Clinicians should be aware that anorexia is a possible adverse effect of minoxidil in this patient population when initiating the drug in similar patients. © 2014 Pharmacotherapy Publications, Inc.

New drug therapies interfering with the renin-angiotensin-aldosterone system for resistant hypertension.

PubMed

Monge, Matthieu; Lorthioir, Aurélien; Bobrie, Guillaume; Azizi, Michel

2013-12-01

There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin-angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension.

Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes – Mechanisms, Management, and Clinical Considerations

PubMed Central

Low Wang, Cecilia C.; Hess, Connie N.; Hiatt, William R.; Goldfine, Allison B.

2016-01-01

Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multi-factorial risk reduction with statins and other lipid lowering agents, anti-hypertensive therapies, and anti-hyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes than for those without. This review considers the mechanisms, history, controversies, new pharmacologic agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes and heart disease outside of the acute care setting. PMID:27297342

Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency.

PubMed

Anker, Stefan D; Schroeder, Stefan; Atar, Dan; Bax, Jeroen J; Ceconi, Claudio; Cowie, Martin R; Crisp, Adam; Dominjon, Fabienne; Ford, Ian; Ghofrani, Hossein-Ardeschir; Gropper, Savion; Hindricks, Gerhard; Hlatky, Mark A; Holcomb, Richard; Honarpour, Narimon; Jukema, J Wouter; Kim, Albert M; Kunz, Michael; Lefkowitz, Martin; Le Floch, Chantal; Landmesser, Ulf; McDonagh, Theresa A; McMurray, John J; Merkely, Bela; Packer, Milton; Prasad, Krishna; Revkin, James; Rosano, Giuseppe M C; Somaratne, Ransi; Stough, Wendy Gattis; Voors, Adriaan A; Ruschitzka, Frank

2016-05-01

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Safety and efficacy of doxazosin as an "add-on" antihypertensive therapy in mild to moderate heart failure patients.

PubMed

Spoladore, Roberto; Roccaforte, Rosa; Fragasso, Gabriele; Gardini, Chiara; Palloshi, Altin; Cuko, Amarild; Arioli, Francesco; Salerno, Anna; Margonato, Alberto

2009-08-01

Doxazosin treatment has been discouraged in hypertensive patients in order to prevent heart failure (HF) development. However, this drug is still prescribed as an "add-on" medication to achieve a better blood pressure (BP) control. The aim of this study was to evaluate the safety and efficacy of doxazosin as an "add-on" medication in HF patients with uncontrolled hypertension. We reviewed our HF clinic files to collect patient variables recorded at baseline and during follow-up visits in patients receiving, or not, doxazosin. We compared HF-related hospitalization rates and all-cause and cardiovascular mortality rates between patients on doxazosin and those not on doxazosin. We constructed cumulative risk curves for time to first event (HF-related hospitalization and/or death) for both groups of patients. Fifty-two HF patients had been prescribed doxazosin. At baseline, several relevant variables were unevenly distributed between patients receiving doxazosin and those not receiving doxazosin (N=122), such as left ventricular ejection fraction (LVEF) and NYHA class. HF-related hospitalization and death rates were similar between patients on doxazosin and those not on doxazosin at the end of the follow-up. Even after adjustment for all potentially confounding variables, doxazosin was not associated with HF-related hospitalization and/or death. Doxazosin significantly reduced BP, but did not affect NYHA class. Doxazosin, "on top" of other antihypertensive treatments was safe and effective, and did not appear to be associated with HF-related hospitalization and mortality rates in our patients with mild/moderate HF.

Diuretics for Hypertension: A Review and Update.

PubMed

Roush, George C; Sica, Domenic A

2016-10-01

This review and update focuses on the clinical features of hydrochlorothiazide (HCTZ), the thiazide-like agents chlorthalidone (CTDN) and indapamide (INDAP), potassium-sparing ENaC inhibitors and aldosterone receptor antagonists, and loop diuretics. Diuretics are the second most commonly prescribed class of antihypertensive medication, and thiazide-related diuretics have increased at a rate greater than that of antihypertensive medications as a whole. The latest hypertension guidelines have underscored the importance of diuretics for all patients, but particularly for those with salt-sensitive and resistant hypertension. HCTZ is 4.2-6.2 systolic mm Hg less potent than CTDN, angiotensin-converting enzyme inhibitors, beta blockers, and calcium channel blockers by 24-hour measurements and 5.1mm Hg systolic less potent than INDAP by office measurements. For reducing cardiovascular events (CVEs), HCTZ is less effective than enalapril and amlodipine in randomized trials, and, in network analysis of trials, it is less effective than CTDN and HCTZ-amiloride. Combined with thiazide-type diuretics, potassium-sparing agents decrease ventricular ectopy and reduce the risk for sudden cardiac death relative to thiazide-type diuretics used alone. A recent synthesis of 44 trials has shown that the relative potencies in milligrams among spironolactone (SPIR), amiloride, and eplerenone (EPLER) are approximately from 25 to 10 to 100, respectively, which may be important when SPIR is poorly tolerated. SPIR reduces proteinuria beyond that provided by other renin angiotensin aldosterone inhibitors. EPLER also reduces proteinuria and has beneficial effects on endothelial function. While guidelines often do not differentiate among specific diuretics, this review demonstrates that these distinctions are important for managing hypertension. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Daily potassium intake and sodium-to-potassium ratio in the reduction of blood pressure: a meta-analysis of randomized controlled trials.

PubMed

Binia, Aristea; Jaeger, Jonathan; Hu, Youyou; Singh, Anurag; Zimmermann, Diane

2015-08-01

To evaluate the efficacy of daily potassium intake on decreasing blood pressure in non-medicated normotensive or hypertensive patients, and to determine the relationship between potassium intake, sodium-to-potassium ratio and reduction in blood pressure. Mixed-effect meta-analyses and meta-regression models. Medline and the references of previous meta-analyses. Randomized controlled trials with potassium supplementation, with blood pressure as the primary outcome, in non-medicated patients. Fifteen randomized controlled trials of potassium supplementation in patients without antihypertensive medication were selected for the meta-analyses (917 patients). Potassium supplementation resulted in reduction of SBP by 4.7 mmHg [95% confidence interval (CI) 2.4-7.0] and DBP by 3.5 mmHg (95% CI 1.3-5.7) in all patients. The effect was found to be greater in hypertensive patients, with a reduction of SBP by 6.8 mmHg (95% CI 4.3-9.3) and DBP by 4.6 mmHg (95% CI 1.8-7.5). Meta-regression analysis showed that both increased daily potassium excretion and decreased sodium-to-potassium ratio were associated with blood pressure reduction (P < 0.05). Increased total daily potassium urinary excretion from 60 to 100 mmol/day and decrease of sodium-to-potassium ratio were shown to be necessary to explain the estimated effect. Potassium supplementation is associated with reduction of blood pressure in patients who are not on antihypertensive medication, and the effect is significant in hypertensive patients. The reduction in blood pressure significantly correlates with decreased daily urinary sodium-to-potassium ratio and increased urinary potassium. Patients with elevated blood pressure may benefit from increased potassium intake along with controlled or decreased sodium intake.

A MULTI-CENTER CLUSTER-RANDOMIZED TRIAL OF A MULTI-FACTORIAL INTERVENTION TO IMPROVE ANTIHYPERTENSIVE MEDICATION ADHERENCE AND BLOOD PRESSURE CONTROL AMONG PATIENTS AT HIGH CARDIOVASCULAR RISK (The COM99 study)*

PubMed Central

Pladevall, Manel; Brotons, Carlos; Gabriel, Rafael; Arnau, Anna; Suarez, Carmen; de la Figuera, Mariano; Marquez, Emilio; Coca, Antonio; Sobrino, Javier; Divine, George; Heisler, Michele; Williams, L Keoki

2010-01-01

Background Medication non-adherence is common and results in preventable disease complications. This study assesses the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events. Methods and Results In this multi-center, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients’ pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end-point of all cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62; 95% confidence interval [CI] 0.50–0.78) and were more likely to be adherent (OR 1.91; 95% CI 1.19–3.05) when compared with control group patients at 6 months. After five years 16% of the patients in the intervention group and 19% in the control group met the composite end-point (hazard ratio 0.97; 95% CI 0.67–1.39). Conclusions A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events. PMID:20823391

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

PubMed

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

2012-09-01

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

Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial.

PubMed

Liu, Zongjun; Shen, Li; Huang, Weijian; Zhao, Xianxian; Fang, Weiyi; Wang, Changqian; Yin, Zhaofang; Wang, Jianan; Fu, Guosheng; Liu, Xuebo; Jiang, Jianjun; Zhang, Zhihui; Li, Jingbo; Lu, Yingmin; Ge, Junbo

2017-09-01

Available data show that approximately 8%-18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy. This is a multicentre, randomised, open-label, parallel-group, active controlled trial that will investigate the efficacy and safety of a 5F saline-irrigated radiofrequency ablation (RFA) used for RDN in the treatment of Chinese patients with resistant hypertension. A total of 254 patients who have failed pharmacological therapy will be enrolled. Eligible subjects will be randomised in a 1:1 ratio to undergo RDN using the RFA plus antihypertensive medication or to receive treatment with antihypertensive medication alone. The primary outcome measure is the change in 24 hours average ambulatory systolic blood pressure from baseline to 3 months, comparing the RDN-plus-medication group with the medication-alone group. Important secondary endpoints include the change in office blood pressure from baseline to 6 months after randomisation. Safety endpoints such as changes in renal function will also be evaluated. The full analysis set, according to the intent-to-treat principle, will be established as the primary analysis population. All participants will provide informed consent; the study protocol has been approved by the Independent Ethics Committee for each site. This study is designed to investigate the efficacy and safety of RDN using a 5F saline microirrigated RFA. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of resistant hypertension in China. ClinicalTrials.gov ID: NCT02900729; pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Long-term Effects of Renin-Angiotensin System–Blocking Therapy and a Low Blood Pressure Goal on Progression of Hypertensive Chronic Kidney Disease in African Americans

PubMed Central

Appel, Lawrence J.; Wright, Jackson T.; Greene, Tom; Kusek, John W.; Lewis, Julia B.; Wang, Xuelei; Lipkowitz, Michael S.; Norris, Keith C.; Bakris, George L.; Rahman, Mahboob; Contreras, Gabriel; Rostand, Stephen G.; Kopple, Joel D.; Gabbai, Francis B.; Schulman, Gerald I.; Gassman, Jennifer J.; Charleston, Jeanne; Agodoa, Lawrence Y.

2013-01-01

Background Antihypertensive drugs that block the renin-angiotensin system (angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers) are recommended for patients with chronic kidney disease (CKD). A low blood pressure (BP) goal (BP, <130/80 mm Hg) is also recommended. The objective of this study was to determine the long-term effects of currently recommended BP therapy in 1094 African Americans with hypertensive CKD. Methods Multicenter cohort study following a randomized trial. Participants were 1094 African Americans with hypertensive renal disease (glomerular filtration rate, 20–65 mL/min/1.73 m2). Following a 3×2-factorial trial (1995–2001) that tested 3 drugs used as initial antihypertensive therapy (ACEIs, calcium channel blockers, and β-blockers) and 2 levels of BP control (usual and low), we conducted a cohort study (2002–2007) in which participants were treated with ACEIs to a BP lower than 130/80 mm Hg. The outcome measures were a composite of doubling of the serum creatinine level, end-stage renal disease, or death. Results During each year of the cohort study, the annual use of an ACEI or an angiotensin receptor blocker ranged from 83.7% to 89.0% (vs 38.5% to 49.8% during the trial). The mean BP in the cohort study was 133/78 mm Hg (vs 136/82 mm Hg in the trial). Overall, 567 participants experienced the primary outcome; the 10-year cumulative incidence rate was 53.9%. Of 576 participants with at least 7 years of follow-up, 33.5% experienced a slow decline in kidney function (mean annual decline in the estimated glomerular filtration rate, <1 mL/min/1.73 m2). Conclusion Despite the benefits of renin-angiotensin system–blocking therapy on CKD progression, most African Americans with hypertensive CKD who are treated with currently recommended BP therapy continue to progress during the long term. PMID:18443258

Effect of L-arginine on blood pressure in pregnancy-induced hypertension: a randomized placebo-controlled trial.

PubMed

Neri, Isabella; Jasonni, Valerio M; Gori, Gian Franco; Blasi, Immacolata; Facchinetti, Fabio

2006-05-01

To evaluate the antihypertensive efficacy of L-arginine (L-Arg) repeated infusions in women affected by gestational hypertension. The women were referred to obstetric units in order to assess their clinical conditions and to exclude the presence of severe fetal and/or maternal complications. Inclusion criteria were: maternal age range 16-45 years, diagnosis of gestational hypertension without proteinuria (patients normotensive until the 20th week), and gestational age ranging between 24 and 36 weeks. Each woman was allocated to receive either L-arginine (20 g/500 mL) or placebo treatment through an i.v. line. The infusion was carried out in the morning from 8 a.m. to 10 a.m. and it was repeated for the next four consecutive days. Systolic and diastolic blood pressure values as well as heart rate were recorded with the patient in an upright, seated position at 08:00, 12:00, 16:00 and 20:00 h. Maternal clinical features such as age, height, weight, and gestational age at inclusion were similar between groups. Both systolic and diastolic blood pressures were reduced by treatment, the effect of L-arginine being significantly higher than that of the placebo (systolic values F = 8.59, p < 0.005; diastolic values F = 3.36; p < 0.001). Twenty women assigned to the L-Arg group (32.2%) and 23 to the placebo group (37.7%) were concomitantly treated with antihypertensives before starting the study. Analyzing the subgroup of patients not receiving antihypertensive drugs we found that L-arginine was superior to placebo in lowering systolic (F = 5.42, p < 0.005) and diastolic (F = 2.20, p < 0.005) blood pressure values. In conclusion, these data support the use of L-Arg as an antihypertensive agent for gestational hypertension especially in view of the other beneficial effects nitric oxide donors display in pregnancy. Further, L-Arg seems well tolerated since in this sample none of the patients reported adverse effects requiring study interruption.

Genome-Wide and Gene-Based Meta-Analyses Identify Novel Loci Influencing Blood Pressure Response to Hydrochlorothiazide.

PubMed

Salvi, Erika; Wang, Zhiying; Rizzi, Federica; Gong, Yan; McDonough, Caitrin W; Padmanabhan, Sandosh; Hiltunen, Timo P; Lanzani, Chiara; Zaninello, Roberta; Chittani, Martina; Bailey, Kent R; Sarin, Antti-Pekka; Barcella, Matteo; Melander, Olle; Chapman, Arlene B; Manunta, Paolo; Kontula, Kimmo K; Glorioso, Nicola; Cusi, Daniele; Dominiczak, Anna F; Johnson, Julie A; Barlassina, Cristina; Boerwinkle, Eric; Cooper-DeHoff, Rhonda M; Turner, Stephen T

2017-01-01

This study aimed to identify novel loci influencing the antihypertensive response to hydrochlorothiazide monotherapy. A genome-wide meta-analysis of blood pressure (BP) response to hydrochlorothiazide was performed in 1739 white hypertensives from 6 clinical trials within the International Consortium for Antihypertensive Pharmacogenomics Studies, making it the largest study to date of its kind. No signals reached genome-wide significance (P<5×10 - 8 ), and the suggestive regions (P<10 -5 ) were cross-validated in 2 black cohorts treated with hydrochlorothiazide. In addition, a gene-based analysis was performed on candidate genes with previous evidence of involvement in diuretic response, in BP regulation, or in hypertension susceptibility. Using the genome-wide meta-analysis approach, with validation in blacks, we identified 2 suggestive regulatory regions linked to gap junction protein α1 gene (GJA1) and forkhead box A1 gene (FOXA1), relevant for cardiovascular and kidney function. With the gene-based approach, we identified hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid δ-isomerase 1 gene (HSD3B1) as significantly associated with BP response (P<2.28×10 - 4 ). HSD3B1 encodes the 3β-hydroxysteroid dehydrogenase enzyme and plays a crucial role in the biosynthesis of aldosterone and endogenous ouabain. By amassing all of the available pharmacogenomic studies of BP response to hydrochlorothiazide, and using 2 different analytic approaches, we identified 3 novel loci influencing BP response to hydrochlorothiazide. The gene-based analysis, never before applied to pharmacogenomics of antihypertensive drugs to our knowledge, provided a powerful strategy to identify a locus of interest, which was not identified in the genome-wide meta-analysis because of high allelic heterogeneity. These data pave the way for future investigations on new pathways and drug targets to enhance the current understanding of personalized antihypertensive treatment. © 2016 American Heart Association, Inc.

Doxazosin in the current treatment of hypertension.

PubMed

Wykretowicz, Andrzej; Guzik, Przemyslaw; Wysocki, Henryk

2008-03-01

Evidence from various studies has shown that even a very small reduction in the blood pressure explains the majority of benefits in cardiovascular outcomes. Although doxazosin is a relatively old drug, it is a very effective add-on therapeutic agent. It has been used in a variety of clinical trials, including different groups of hypertensive patients such as diabetics, the elderly, patients with benign prostatic hyperplasia or hypercholesterolaemia, the obese or Afro-Americans and in combination with all major groups of antihypertensive drugs such as: calcium channel antagonists, diuretics, beta-adrenoreceptor antagonists, angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers. The purpose of this article is to review the role of doxazosin in the current treatment of hypertension. English-language reports published in 1986 - 2007 were retrieved. Data extraction was based on articles reporting at least 15 or more patients treated with combination of doxazosin with other antihypertensive drugs. In these studies doxazosin in either standard or extended-release formulation was added as a second- or third-line agent. The two formulations of doxazosin, although chemically identical, appear to differ in some other effects. A large proportion of patients demonstrated a favourable blood pressure response with relatively few treatment-associated side effects showing that this drug appears to be a valuable add-on antihypertensive treatment option. Doxazosin reduces blood pressure and additionally influences other risk factors of coronary heart disease. However, it should be clearly stated that the clinical role of 'beyond blood pressure' effects of doxazosin are largely undetermined.

Renal denervation and hypertension - The need to investigate unintended effects and neural control of the human kidney.

PubMed

Grisk, Olaf

2017-05-01

Increased renal sympathetic nerve activity (RSNA) is present in human and experimental forms of arterial hypertension. Experimental denervation studies showed that renal nerves contribute to the development of hypertension. Clinical trials provided equivocal results on the antihypertensive efficacy of renal denervation in patients spurring discussions on technical aspects of renal denervation and further research on the role of renal nerves for the regulation of kidney function as well as the pathophysiology of hypertension. This review summarizes recent findings on adrenoceptor expression and function in the human kidney, adrenoceptor-dependent regulation of sodium chloride transport in the distal nephron, experimental data on chronic RSNA and the development of high arterial pressure and consequences of renal denervation that may limit its antihypertensive efficacy. Future research needs to reduce the gap between our knowledge on neural control of renal function in animals vs. humans to facilitate translation of experimental animal data to humans. More experimental studies on the temporal relationship between RSNA and arterial pressure in the chronic setting are needed to better define the pathogenetic role of heightened RSNA in different forms of arterial hypertension in order to improve the rational basis for renal denervation in antihypertensive therapy. Finally, research on unintended consequences of renal denervation including but not limited to reinnervation and denervation supersensitivity needs to be intensified to further assess the potential of renal denervation to slow the progression of renal disease and hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of the effects of antihypertensive treatment with angiotensin II blockade and beta-blockade on carotid wall structure and haemodynamics: protocol and baseline demographics.

PubMed

Ariff, Ben; Stanton, Alice; Barratt, Dean; Augst, Alex; Glor, Fadi; Poulter, Neil; Sever, Peter; Xu, Yun; Hughes, Alun; Thom, Simon A Mc G

2002-06-01

Several systemic factors have been shown to contribute to the acceleration of large vessel atheroma. Correction of these factors leads to a reduction in the progression of plaque formation and associated arterial wall thickness. Atheroma remains, however, a focal disease, developing at characteristic sites within the arterial tree. These sites are typically at areas of vessel branching or marked curvature, and correspond to regions of high tensile stress and low sheer stress, leading to the hypothesis that local haemodynamic factors and vessel wall mechanics potentiate the focal development of atheroma. Current assessment of vascular haemodynamics suffers from an inability to handle complex flow, and does not allow accurate determination of locally varying flow, and shear stress patterns. The application of computational fluid dynamic (CFD) flow simulation techniques to ultrasound and local pressure data, however, allows a comprehensive, non-invasive appraisal of haemodynamic flow parameters to be performed. The Candesartan cilexetil and Atenolol Carotid Haemodynamic Endpoint Trial (CACHET) study compares the effects of two antihypertensive regimens, one b-blocker-based, the other angiotensin receptor blocker based, on carotid intima-media thickness. The collection of ultrasound and pressure data on each subject provides a unique opportunity to apply these data to the CFD model to study the effects of these antihypertensive regimens on local fluid dynamics. This will lead to a greater understanding of the relationship of these factors to atheroma formation and regression.

Clinical Trials Update: CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001.

PubMed

Louis, A; Cleland, J G; Crabbe, S; Ford, S; Thackray, S; Houghton, T; Clark, A

2001-06-01

This is a synopsis of presentations made at the American College of Cardiology (ACC) in 2001 summarising recent research developments relating to heart failure. Clinical studies of particular interest to physicians with an interest in heart failure and its prevention are reviewed. The COPERNICUS trial lends further support to the use of the beta-blocker, carvedilol, in severe heart failure and the CAPRICORN trial to its use in patients with post-infarction left ventricular systolic dysfunction. The MIRACLE study reinforces the evidence from three smaller trials that cardiac resynchronisation therapy is an effective treatment for the relief of symptoms in patients with severe heart failure and cardiac dyssynchrony. The STAF trial casts further doubt on the wisdom of cardioversion as a routine strategy for the management of chronic atrial fibrillation. The RITZ-2 trial suggests that an intravenous, non-selective endothelin antagonist is effective in improving haemodynamics and symptoms and possibly in reducing morbidity in severe heart failure. Observational studies in heart failure suggest that a moderate excess of body fat and elevated blood cholesterol may be desirable in patients with heart failure, challenging the current non-evidenced-based vogue for cholesterol lowering therapy in heart failure. The RENAISSANCE and RECOVER outcome studies of etanercept, a tumour necrosis factor (TNF) receptor analogue that blocks the effect of TNF, were stopped because of lack of evidence of benefit shortly after the ACC.

Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007-2010.

PubMed

Kent, Shia T; Shimbo, Daichi; Huang, Lei; Diaz, Keith M; Kilgore, Meredith L; Oparil, Suzanne; Muntner, Paul

2014-01-01

After the 2003 publication of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines, there was a 5-10% increase in patients initiating antihypertensive medication with a thiazide-type diuretic, but most patients still did not initiate treatment with this class. There are few contemporary published data on antihypertensive medication classes filled by patients initiating treatment. We used the 5% random Medicare sample to study the initiation of antihypertensive medication between 2007 and 2010. Initiation was defined by the first antihypertensive medication fill preceded by 365 days with no antihypertensive medication fills. We restricted our analysis to beneficiaries ≥ 65 years who had two or more outpatient visits with a hypertension diagnosis and full Medicare fee-for-service coverage for the 365 days prior to initiation of antihypertensive medication. Between 2007 and 2010, 32,142 beneficiaries in the 5% Medicare sample initiated antihypertensive medication. Initiation with a thiazide-type diuretic decreased from 19.2% in 2007 to 17.9% in 2010. No other changes in medication classes initiated occurred over this period. Among those initiating antihypertensive medication in 2010, 31.3% filled angiotensin-converting enzyme inhibitors (ACE-Is), 26.9% filled beta blockers, 17.2% filled calcium channel blockers, and 14.4% filled angiotensin receptor blockers (ARBs). Initiation with >1 antihypertensive medication class decreased from 25.6% in 2007 to 24.1% in 2010. Patients initiated >1 antihypertensive medication class most commonly with a thiazide-type diuretic and either an ACE-I or ARB. These results suggest that JNC 7 had a limited long-term impact on the choice of antihypertensive medication class and provide baseline data prior to the publication of the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8).

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey).

PubMed

Bress, Adam P; Kramer, Holly; Khatib, Rasha; Beddhu, Srinivasan; Cheung, Alfred K; Hess, Rachel; Bansal, Vinod K; Cao, Guichan; Yee, Jerry; Moran, Andrew E; Durazo-Arvizu, Ramon; Muntner, Paul; Cooper, Richard S

2017-04-25

SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of <120 versus <140 mm Hg among US adults at high cardiovascular disease risk but without diabetes mellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate <20 mL·min -1 ·1.73 m -2 , or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events. © 2017 American Heart Association, Inc.

A Randomized Trial of Heart Failure Disease Management in Skilled Nursing Facilities: Design and Rationale

PubMed Central

Boxer, Rebecca S.; Dolansky, Mary A.; Bodnar, Christine A.; Singer, Mendel E.; Albert, Jeffery M.; Gravenstein, Stefan

2013-01-01

Background Heart failure disease management can improve health outcomes for older community dwelling patients with heart failure. Heart failure disease management has not been studied in skilled nursing facilities, a major site of transitional care for older adults. Methods and Anticipated Results The objective of this trial is to investigate if a heart failure disease management program (HF-DMP) in skilled nursing facilities (SNF) will decrease all-cause rehospitalizations for the first 60 days post SNF admission. The trial is a randomized cluster trial to be conducted in 12 for-profit SNF in the greater Cleveland area. The study population is inclusive of patients with heart failure regardless of ejection fraction but excludes those patients on dialysis and with a life expectancy of 6 months or less. The HF-DMP includes 7 elements considered standard of care for patients with heart failure: documentation of left ventricular function, tracking of weight and symptoms, medication titration, discharge instructions, 7 day follow up appointment post SNF discharge, patient education. The HF-DMP is conducted by a research nurse tasked with adhering to each element of the program and regularly audited to maintain fidelity of the program. Additional outcomes include health status, self-care management, and discharge destination. Conclusion The SNF-Connect Trial is the first trial of its kind to assess if a HF-DMP will improve outcomes for patients in SNFs. This trial will provide evidence on the effectiveness of HF-DMP to improve outcomes for older frail heart failure patients undergoing post-acute rehabilitation. PMID:23871475

Azilsartan medoxomil: a review of its use in hypertension.

PubMed

Perry, Caroline M

2012-09-01

Azilsartan medoxomil (Edarbi®; Ipreziv™) is an orally administered angiotensin II receptor type 1 antagonist (blocker) used in the treatment of adults with essential hypertension. This article reviews data on the clinical efficacy and tolerability of azilsartan medoxomil in adults with essential hypertension and provides a summary of its pharmacological properties. Azilsartan medoxomil is a prodrug that undergoes rapid hydrolysis in the gastrointestinal tract after oral administration to the bioactive moiety azilsartan, before systemic absorption. Azilsartan medoxomil produces antihypertensive effects by selectively blocking the binding of angiotensin II to the angiotensin type 1 (AT(1)) receptor, thereby antagonizing the pressor response activity of angiotensin II. In vitro, azilsartan produced greater and more sustained AT(1) receptor binding/blockade activity than several comparator angiotensin II receptor antagonists. Azilsartan medoxomil reduces blood pressure (BP) in hypertensive adults. In addition, the drug has been shown to have pleiotropic effects (i.e. effects beyond AT(1) receptor blockade). In adults with essential hypertension, azilsartan medoxomil 20, 40 or 80 mg effectively reduced BP over a 24-hour period with once-daily administration in three major, randomized, controlled trials in which the primary endpoints were changes from baseline in 24-hour mean systolic BP (SBP) at week 6 (two trials) or week 24, assessed by ambulatory BP monitoring (ABPM). In the two 6-week trials, azilsartan medoxomil showed dose-dependent efficacy over all evaluated dosages and was more effective than placebo in lowering SBP. At the maximum approved dosage of 80 mg once daily, azilsartan medoxomil was significantly more effective than maximum dosages of olmesartan medoxomil (40 mg once daily) or valsartan (320 mg once daily), based on primary endpoint assessments. Mean reductions in clinic measurements of SBP and diastolic BP (DBP) measurements were also generally greater with azilsartan medoxomil 80 mg once daily than with the comparator drugs in these 6-week studies. Over a longer treatment period of 24 weeks, azilsartan medoxomil showed sustained BP-lowering efficacy, with the reduction in 24-hour mean SBP at week 24 significantly greater with azilsartan medoxomil 40 or 80 mg once daily than with valsartan 320 mg once daily. Mean reductions from baseline in mean clinic SBP and DBP as well as DBP by ABPM were also significantly greater with azilsartan medoxomil 40 or 80 mg once daily than with valsartan. Azilsartan medoxomil was generally well tolerated, with a tolerability profile similar to that of placebo in the 6-week trials. Across the three major trials, headache and dizziness were among the most common adverse events. Overall, rates of treatment discontinuation as a result of adverse events were low in the 6-week and 24-week trials. In conclusion, once-daily azilsartan medoxomil effectively lowers BP in adults with essential hypertension and has shown better antihypertensive efficacy than maximum therapeutic dosages of olmesartan medoxomil or valsartan in major trials of up to 24 weeks' duration. Azilsartan medoxomil is generally well tolerated and the low rates of discontinuation due to adverse events suggest that patients are likely to persist with long-term treatment. Azilsartan medoxomil is therefore a useful and attractive new option for lowering BP in patients with essential hypertension, particularly for those not able to tolerate other antihypertensive drugs. Further studies are required to evaluate the effects of azilsartan medoxomil on cardiovascular morbidity and mortality.

Long-term renal and cardiovascular outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants by baseline estimated GFR.

PubMed

Rahman, Mahboob; Ford, Charles E; Cutler, Jeffrey A; Davis, Barry R; Piller, Linda B; Whelton, Paul K; Wright, Jackson T; Barzilay, Joshua I; Brown, Clinton D; Colon, Pedro J; Fine, Lawrence J; Grimm, Richard H; Gupta, Alok K; Baimbridge, Charles; Haywood, L Julian; Henriquez, Mario A; Ilamaythi, Ekambaram; Oparil, Suzanne; Preston, Richard

2012-06-01

CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone. This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged ≥55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4-8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m(2)) as follows: normal/increased (≥90; n=8027), mild reduction (60-89; n=17,778), and moderate/severe reduction (<60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD. After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P<0.001). In participants with an eGFR <60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD. CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.

Interventional Therapies for Resistant Hypertension: A Brief Update

PubMed Central

Brandon, Lisa

2016-01-01

Resistant hypertension remains a clinical challenge with few management options beyond maximisation of medications. Catheter- based renal artery denervation (RDN) was proposed in 2009 as a possible therapy for resistant hypertension and early feasibility trials caused excitement among cardiologists and antihypertensive specialists, showing remarkable and sustained blood pressure reductions. In 2014, enthusiasm for RDN dampened following the SYMPLICITY 3 trial results, which showed no statistically significant difference in blood pressure between the intervention and control arms. However, hope remains for the improved management of resistant hypertension; procedural understanding, technological advancements and alternative targets – such as baroreceptor activation therapy and arteriovenous shunts – may aid the identification of those patients for whom specific interventional therapies will be effective. PMID:29588709

Relationship between sponsorship and failure rate of dental implants: a systematic approach.

PubMed

Popelut, Antoine; Valet, Fabien; Fromentin, Olivier; Thomas, Aurélie; Bouchard, Philippe

2010-04-21

The number of dental implant treatments increases annually. Dental implants are manufactured by competing companies. Systematic reviews and meta-analysis have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. So far, the impact of industry sponsorship on the outcomes and conclusions of dental implant clinical trials has never been explored. The aim of the present study was to examine financial sponsorship of dental implant trials, and to evaluate whether research funding sources may affect the annual failure rate. A systematic approach was used to identify systematic reviews published between January 1993 and December 2008 that specifically deal with the length of survival of dental implants. Primary articles were extracted from these reviews. The failure rate of the dental implants included in the trials was calculated. Data on publication year, Impact Factor, prosthetic design, periodontal status reporting, number of dental implants included in the trials, methodological quality of the studies, presence of a statistical advisor, and financial sponsorship were extracted by two independent reviewers (kappa = 0.90; CI(95%) [0.77-1.00]). Univariate quasi-Poisson regression models and multivariate analysis were used to identify variables that were significantly associated with failure rates. Five systematic reviews were identified from which 41 analyzable trials were extracted. The mean annual failure rate estimate was 1.09%.(CI(95%) [0.84-1.42]). The funding source was not reported in 63% of the trials (26/41). Sixty-six percent of the trials were considered as having a risk of bias (27/41). Given study age, both industry associated (OR = 0.21; CI(95%) [0.12-0.38]) and unknown funding source trials (OR = 0.33; (CI(95%) [0.21-0.51]) had a lower annual failure rates compared with non-industry associated trials. A conflict of interest statement was disclosed in 2 trials. When controlling for other factors, the probability of annual failure for industry associated trials is significantly lower compared with non-industry associated trials. This bias may have significant implications on tooth extraction decision making, research on tooth preservation, and governmental health care policies.

The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

PubMed

Eichhorn, Eric J; Bristow, Michael R

2001-01-01

Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of beta-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of beta-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction.

The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial

PubMed Central

Eichhorn, Eric J; Bristow, Michael R

2001-01-01

Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of β-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of β-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction. PMID:11806769

Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus - Mechanisms, Management, and Clinical Considerations.

PubMed

Low Wang, Cecilia C; Hess, Connie N; Hiatt, William R; Goldfine, Allison B

2016-06-14

Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes mellitus exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multifactorial risk reduction with statins and other lipid-lowering agents, antihypertensive therapies, and antihyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes mellitus than for those without. This review considers the mechanisms, history, controversies, new pharmacological agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes mellitus and heart disease outside of the acute care setting. © 2016 American Heart Association, Inc.

Gender differences in hypertension awareness, antihypertensive use and blood pressure control in Bangladeshi adults: findings from a national cross-sectional survey.

PubMed

Rahman, Muntasirur; Williams, Gail; Al Mamun, Abdullah

2017-05-25

Bangladesh is facing an epidemiological transition with a growing burden of non-communicable diseases. Traditionally, hypertension and associated complications in women receive less recognition, and there is a dearth of related publications. The study aims to explore gender differences in high blood pressure awareness and antihypertensive use in Bangladeshi adults at the community level. Another objective is to identify factors associated with uncontrolled hypertension among antihypertensive users. Data from the Bangladesh Demographic and Health Survey (BDHS 2011) was analysed. From a nationally representative sample of 3870 males and 3955 females, aged ≥35 years, blood pressure and related information were collected following WHO guidelines. Logistic regression models were used to estimate adjusted odds ratio (AOR) for factors affecting blood pressure awareness, antihypertensive use and uncontrolled hypertension among males and females taking antihypertensive medications. All analyses were weighted according to the complex survey design. Women were more likely to have their blood pressure measured (76% vs. males 71%, p < 0.001) and to be 'aware' about their own high BP (55% vs. males 43%, p < 0.001). No gender difference was observed in antihypertensive medication use among those who were aware of their own high BP (females 67%, males 65%, p = 0.39). Non-working females were less likely to use antihypertensive (67% vs. non-working males 77%, p < 0.05). Poor women were worse off compared with poor males in antihypertensive medication use. One-in-three antihypertensive medication users had stage 2 hypertension (SBP ≥160/DBP ≥100 mmHg). Female sex, older age, increased wealth, higher BMI and certain geographical regions were associated with poor blood pressure control among antihypertensive medication users. BP check-ups and hypertension awareness were higher among women than men but did not translate into better antihypertensive medication practice. Gender disadvantage and inequity were observed in antihypertensive medication use. Our findings reiterate the importance of sex-disaggregated analysis and reporting. Policy makers should explore the uncontrolled hypertension burden and geographical variations in Bangladesh.

The effects of blood pressure reduction in older patients: an overview of five randomized controlled trials in elderly hypertensives.

PubMed

MacMahon, S; Rodgers, A

1993-11-01

Direct evidence about the effects of antihypertensive treatment on vascular disease in older patients is available from five randomized trials conducted exclusively in patients over the age of 60 years. These trials involved a total of 12,483 individuals with systolic or diastolic hypertension (mean age = 72 years, mean entry blood pressure = 181/88 mmHg). Over an average follow-up period of 4.7 years, a 15/6 mmHg difference in blood pressure between study and control groups was achieved. Among those patients assigned active treatment, stroke incidence was reduced by 34% SD6 and coronary heart disease incidence was reduced by 19% SD7. These proportional reductions were of similar size to those observed in trials in predominantly younger patients. However, the absolute benefits observed in older patients were more than twice as great as those observed in younger patients. The results suggest that over 10 years, treatment would prevent at least one major vascular event among every 10 elderly patients at similar risk to those enrolled in the trials.

Anti-hypertensive treatment prolongs tPA door-to-treatment time: Secondary analysis of the INSTINCT trial.

PubMed Central

Skolarus, Lesli E.; Scott, Phillip A.; Burke, James F.; Adelman, Eric E.; Frederiksen, Shirley M.; Kade, Allison M.; Kalbfleisch, Jack D.; Ford, Andria L.; Meurer, William J.

2012-01-01

Background/Purpose Identifying modifiable tPA treatment delays may improve stroke outcomes. We hypothesized that pre-thrombolytic anti-hypertensive treatment (AHT) may prolong door-to-treatment time (DTT). Methods Analysis of consecutive tPA-treated patients at 24 randomly selected community hospitals in the INSTINCT trial between 2007-2010. DTTs among stroke patients who received pre-thrombolytic AHT were compared to those that did not receive pre-thrombolytic AHT. We then calculated a propensity score for the probability of receiving pre-thrombolytic AHT using logistic regression with demographics, stroke risk factors, home medications, stroke severity (NIHSS), onset-to-door time, admission glucose, pretreatment blood pressure, EMS transport and location at time of stroke as independent variables. A paired t-test was performed to compare the DTTs between the propensity matched groups. Results Of 534 tPA treated stroke patients analyzed, 95 received pre-thrombolytic AHT. In the unmatched cohort, patients who received pre-thrombolytic AHT had a longer DTT (mean increase 9 minutes; 95% confidence interval (CI) 2-16 minutes) than patients who did not. After propensity matching, patients who received pre-thrombolytic AHT had a longer DTT (mean increase 10.4 minutes, 95% CI 1.9 - 18.8) than patients who did not receive pre-thrombolytic AHT. Conclusion Pre-thrombolytic AHT is associated with modest delays in DTT. This represents a potential target for quality improvement initiatives. Further research evaluating optimum pre-thrombolytic hypertension management is warranted. PMID:23033348

Antihypertensive treatment prolongs tissue plasminogen activator door-to-treatment time: secondary analysis of the INSTINCT trial.

PubMed

Skolarus, Lesli E; Scott, Phillip A; Burke, James F; Adelman, Eric E; Frederiksen, Shirley M; Kade, Allison M; Kalbfleisch, Jack D; Ford, Andria L; Meurer, William J

2012-12-01

Identifying modifiable tissue plasminogen activator treatment delays may improve stroke outcomes. We hypothesized that prethrombolytic antihypertensive treatment (AHT) may prolong door-to-treatment time (DTT). We performed an analysis of consecutive tissue plasminogen activator-treated patients at 24 randomly selected community hospitals in the Increasing Stroke Treatment through Interventional Behavior Change Tactics (INSTINCT) trial between 2007 and 2010. DTT among stroke patients who received prethrombolytic AHT were compared with those who did not receive prethrombolytic AHT. We then calculated a propensity score for the probability of receiving prethrombolytic AHT using logistic regression with demographics, stroke risk factors, home medications, stroke severity (National Institutes of Health Stroke Scale), onset-to-door time, admission glucose, pretreatment blood pressure, emergency medical service transport, and location at time of stroke as independent variables. A paired t test was performed to compare the DTT between the propensity-matched groups. Of 534 tissue plasminogen activator-treated stroke patients analyzed, 95 received prethrombolytic AHT. In the unmatched cohort, patients who received prethrombolytic AHT had a longer DTT (mean increase, 9 minutes; 95% confidence interval, 2-16 minutes) than patients who did not. After propensity matching, patients who received prethrombolytic AHT had a longer DTT (mean increase, 10.4 minutes; 95% confidence interval, 1.9-18.8) than patients who did not receive prethrombolytic AHT. Prethrombolytic AHT is associated with modest delays in DTT. This represents a potential target for quality-improvement initiatives. Further research evaluating optimum prethrombolytic hypertension management is warranted.

EARLY Treatment with azilsartan compared to ACE-inhibitors in anti-hypertensive therapy – rationale and design of the EARLY hypertension registry

PubMed Central

2013-01-01

Background Arterial hypertension is highly prevalent but poorly controlled. Blood pressure (BP) reduction substantially reduces cardiovascular morbidity and mortality. Recent randomized, double-blind clinical trials demonstrated that azilsartan medoxomil (AZM) is more effective in reducing BP than the ubiquitary ACE inhibitor ramipril. Therefore, we aimed to test whether these can be verified under clinical practice conditions. Methods/Design The “Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy” (EARLY) registry is a prospective, observational, national, multicenter registry with a follow-up of up to 12 months. It will include up to 5000 patients on AZM or ACE-inhibitor monotherapy in a ratio of 7 to 3. A subgroup of patients will undergo 24-hour BP monitoring. EARLY has two co-primary objectives: 1) Description of the safety profile of azilsartan and 2) achievement of BP targets based on recent national and international guidelines for patients treated with azilsartan in comparison to those treated with ACE-inhibitors. The most important secondary endpoints are the determination of persistence with treatment and the documentation of cardiovascular and renal events. Recruitment commenced in January 2012 and will be completed by February 2013. Conclusions The data obtained will supplement previous results from randomized controlled trials to document the potential value of utilizing azilsartan medoxomil in comparison to ACE-inhibitor treatment for target BP achievement in clinical practice. PMID:23819631

[Prevalence of hypertension in elderly long-term care residents in Spain. The Geriatric HTA study].

PubMed

Martín-Baranera, Montserrat; Sánchez Ferrín, Pau; Armario, Pedro

2006-11-11

This study aimed to estimate the prevalence of hypertension in elderly long-term care residents in Spain and to describe such population in terms of comorbidity and hypertension treatment and control. A countrywide cross-sectional study was conducted in May 2003 among long-term care residents aged 65 or more. Patients in palliative care units were excluded. Hypertension was defined in patients who fulfilled at least one of the following criteria: diagnosis of hypertension on the medical record, antihypertensive medication and/or highest blood pressure values during the previous year > or = 140/90 mmHg. Overall, 13,272 subjects - mean age (standard deviation) 82.9 (7.5) years (range: 65-106 years) - were included from 223 centres; 70.6% were women. Almost 2 thirds of patients met at least one hypertension criterion (8,242 patients, 62.1%; 95% confidence interval, 61.3-62.9%). In those patients, other frequent cardiovascular risk factors were obesity (26.3%), diabetes (25.7%) and dislipemia (23.8%). A concomitant diagnosis of dementia, peripheral vascular disease, stroke or congestive heart failure was present in 37.1%, 28.3%, 26.0% and 25.1%, respectively. The proportion of hypertensive patients receiving at least one antihypertensive drug was 69.7%. Diuretics were the most commonly used agents (46.3%), followed by angiotensine converting enzyme inhibitors (34.6%). The latest blood pressure measurement was < 140/90 mmHg in 60.4% of the hypertensive patients. Elderly long-term care residents in Spain showed a high prevalence of hypertension and other cardiovascular risk factors, and a substantial degree of associated clinical conditions. The proportion of antihypertensive drug therapy was comparable to those reported in similar studies.

The antihypertensive drug hydralazine activates the intrinsic pathway of apoptosis and causes DNA damage in leukemic T cells

PubMed Central

Ruiz-Magaña, María J.; Martínez-Aguilar, Rocío; Lucendo, Estefanía; Campillo-Davo, Diana; Schulze-Osthoff, Klaus; Ruiz-Ruiz, Carmen

2016-01-01

Epigenetic therapies have emerged as promising anticancer approaches, since epigenetic modifications play a major role in tumor initiation and progression. Hydralazine, an approved vasodilator and antihypertensive drug, has been recently shown to act as a DNA methylation inhibitor. Even though hydralazine is already tested in clinical cancer trials, its mechanism of antitumor action remains undefined. Here, we show that hydralazine induced caspase-dependent apoptotic cell death in human p53-mutant leukemic T cells. Moreover, we demonstrate that hydralazine triggered the mitochondrial pathway of apoptosis by inducing Bak activation and loss of the mitochondrial membrane potential. Hydralazine treatment further resulted in the accumulation of reactive oxygen species, whereas a superoxide dismutase mimetic inhibited hydralazine-induced cell death. Interestingly, caspase-9-deficient Jurkat cells or Bcl-2- and Bcl-xL-overexpressing cells were strongly resistant to hydralazine treatment, thereby demonstrating the dependence of hydralazine-induced apoptosis on the mitochondrial death pathway. Furthermore, we demonstrate that hydralazine treatment triggered DNA damage which might contribute to its antitumor effect. PMID:26942461

Drugs affecting blood pressure variability: an update.

PubMed

Hocht, Christian; Del Mauro, Julieta Sofia; Bertera, Facundo Martín; Taira, Carlos Alberto

2015-01-01

Blood pressure variability (BPV) is considered nowadays a novel risk factor for cardiovascular disease. Clinical evidences support that short-term and long-term BPV independently contribute to target organ damage, cardiovascular events and mortality in patients with hypertension or diabetes. Attenuation of excessive fluctuations of systolic and diastolic BPV has been suggested as an additional therapeutic target in cardiovascular prevention. A growing number of preclinical and clinical studies have focused in the assessment of drug effects or other interventions on the different types of BPV and their contribution in the prevention of cardiovascular events. Prospective clinical trials have shown that antihypertensive classes differ in their ability to control excessive BP fluctuations with an impact in clinical outcomes. Current evidences suggest that calcium channel blockers are more effective than other blood pressure lowering drugs for the reduction of short-term, mid-term and long-term BPV. In order to increase actual knowledge regarding the therapeutic significance of BPV in cardiovascular disease, there is a need for additional clinical studies specifically designed for the study of the relevance of short-term and long-term BPV control by antihypertensive drugs.

Left ventricular hypertrophy does not prevent heart failure in experimental hypertension.

PubMed

Hernán Gómez Llambí, H; Cao, G; Donato, M; Suárez, D; Ottaviano, G; Müller, A; Buchholz, B; Gelpi, R; Otero-Losada, M; Milei, J

2017-07-01

Left ventricular hypertrophy (LVH) secondary to hypertension has been accepted to prevent heart failure (HF) while paradoxically increasing cardiovascular morbi-mortality. To evaluate whether antihypertensive treatment inhibits LVH, restores beta-adrenergic response and affects myocardial oxidative metabolism. Ninety spontaneously hypertensive rats (SHR) were distributed into groups and treated (mg/kg, p.o.) with: losartan 30 (L), hydralazine 11 (H), rosuvastatin 10 (R), carvedilol 20 (C). Hypertension control group comprised 18 normotensive rats (Wistar-Kyoto, WKY). Following euthanasia at 16months, contractility was measured in 50% of rats (Langendorff system) before and after isoproterenol (Iso) 10 -9 M, 10 -7 M and 10 -5 M stimulation. Left ventricular weight (LVW) was measured in the remaining hearts, and normalized by BW. Expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2), glutaredoxin 3 (Grx-3), caspase-3 and brain natriuretic peptide (BNP) was determined. Systolic blood pressure (mmHg): 154±3 (L), 137±1 (H), 190±3 (R)*, 206±3 (SHR)*, 183±1 (C)**, and 141±1 (WKY) (*p<0.05 vs. L, H, WKY, **p<0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p<0.05). Groups SHR, R and C evidenced baseline contractile depression. Response to Iso 10 -5 M was similar in WKY and L. Expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (p<0.01). Present findings argue against the traditional idea and support that LVH might not be required to prevent HF. Increased expression of thioredoxins by antihypertensive treatment might be involved in protection from HF. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus: The Anglo Scandinavian Cardiac Outcomes Trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Collaborative Atorvastatin Diabetes Study.

PubMed

Kaasenbrood, Lotte; Poulter, Neil R; Sever, Peter S; Colhoun, Helen M; Livingstone, Shona J; Boekholdt, S Matthijs; Pressel, Sara L; Davis, Barry R; van der Graaf, Yolanda; Visseren, Frank L J

2016-05-01

In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events. Data of 2725 patients with type 2 diabetes mellitus from the Lipid Lowering Arm of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) study (atorvastatin 10 mg versus placebo) were used for model derivation. The model was based on 8 clinical predictors including treatment allocation (statin/placebo). Ten-year individualized ARR on major cardiovascular events by statin therapy were calculated for each patient by subtracting the estimated on-treatment risk from the estimated off-treatment risk. Predicted 10-year ARR by statin therapy was <2% for 13% of the patients. About 30% had an ARR of >4% (median ARR, 3.2%; interquartile range, 2.5%-4.3%; 95% confidence interval for 3.2% ARR, -1.4% to 6.8%). Addition of treatment interactions did not improve model performance. Therefore, the wide distribution in ARR was a consequence of the underlying distribution in cardiovascular risk enrolled in these trials. External validation of the model was performed in data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT; pravastatin 40 mg versus usual care) and Collaborative Atorvastatin Diabetes Study (CARDS; atorvastatin 10 mg versus placebo) of 3878 and 2838 patients with type 2 diabetes mellitus, respectively. Model calibration was adequate in both external data sets, discrimination was moderate (ALLHAT-LLT: c-statistics, 0.64 [95% confidence interval, 0.61-0.67] and CARDS: 0.68 [95% confidence interval, 0.64-0.72]). ARRs of major cardiovascular events by statin therapy can be accurately estimated for individual patients with type 2 diabetes mellitus using a model based on routinely available patient characteristics. There is a wide distribution in ARR that may complement informed decision making. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00327418 (CARDS) and NCT00000542 (ALLHAT). © 2016 American Heart Association, Inc.

Translation failure and medical reversal: Two sides to the same coin.

PubMed

Prasad, Vinay

2016-01-01

Translation failure occurs when the results of preclinical, observational and/or early phase studies fail to predict the results of well done (i.e. appropriately controlled, adequately powered, and properly conducted) phase III or randomised clinical trials. Some failures occur when promising basic science findings fail to replicate in human studies, while others happen when promising uncontrolled trial data show an exaggerated effect that vanishes in the setting of a randomised trial. Medical reversals occur when the results of preclinical, observational and/or early phase studies fail to predict the results of subsequent randomized clinical trials, but the practice has already gained widespread acceptance. Oncologic examples include bevacizumab and the use of autologous stem cell transplant in metastatic breast cancer. In a well-intentioned effort to reduce the rate of translation failure, oncologists must be careful that changes to regulatory processes and clinical trial design do not actually work to increase the approval of ineffective compounds. By trying to cure translation failure, we should be careful to avoid medical reversal. The rise of surrogate end-points and role of hard-wired bias in oncology trials suggest that we may be currently ignoring the simple fact that translation failure and medical reversal are two sides to the same coin. Published by Elsevier Ltd.

Eplerenone for hypertension.

PubMed

Tam, Tina Sc; Wu, May Hy; Masson, Sarah C; Tsang, Matthew P; Stabler, Sarah N; Kinkade, Angus; Tung, Anthony; Tejani, Aaron M

2017-02-28

Eplerenone is an aldosterone receptor blocker that is chemically derived from spironolactone. In Canada, it is indicated for use as adjunctive therapy to reduce mortality for heart failure patients with New York Heart Association (NYHA) class II systolic chronic heart failure and left ventricular systolic dysfunction. It is also used as adjunctive therapy for patients with heart failure following myocardial infarction. Additionally, it is indicated for the treatment of mild and moderate essential hypertension for patients who cannot be treated adequately with other agents. It is important to determine the clinical impact of all antihypertensive medications, including aldosterone antagonists, to support their continued use in essential hypertension. No previous systematic reviews have evaluated the effect of eplerenone on cardiovascular morbidity, mortality, and magnitude of blood pressure lowering in patients with hypertension. To assess the effects of eplerenone monotherapy versus placebo for primary hypertension in adults. Outcomes of interest were all-cause mortality, cardiovascular events (fatal or non-fatal myocardial infarction), cerebrovascular events (fatal or non fatal strokes), adverse events or withdrawals due to adverse events, and systolic and diastolic blood pressure. We searched the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registers up to 3 March 2016. We handsearched references from retrieved studies to identify any studies missed in the initial search. We also searched for unpublished data by contacting the corresponding authors of the included studies and pharmaceutical companies involved in conducting studies on eplerenone monotherapy in primary hypertension. The search had no language restrictions. We selected randomized placebo-controlled trials studying adult patients with primary hypertension. We excluded studies in people with secondary or gestational hypertension and studies where participants were receiving multiple antihypertensives. Three review authors independently reviewed the search results for studies meeting our criteria. Three review authors independently extracted data and assessed trial quality using a standardized data extraction form. A fourth independent review author resolved discrepancies or disagreements. We performed data extraction and synthesis using a standardized format on Covidence. We conducted data analysis using Review Manager 5. A total of 1437 adult patients participated in the five randomized parallel group studies, with treatment durations ranging from 8 to 16 weeks. The daily doses of eplerenone ranged from 25 mg to 400 mg daily. Meta-analysis of these studies showed a reduction in systolic blood pressure of 9.21 mmHg (95% CI -11.08 to -7.34; I 2 = 58%) and a reduction of diastolic pressure of 4.18 mmHg (95% CI -5.03 to -3.33; I 2 = 0%) (moderate quality evidence).There may be a dose response effect for eplerenone in the reduction in systolic blood pressure at doses of 400 mg/day. However, this finding is uncertain, as it is based on a single included study with low quality evidence. Overall there does not appear to be a clinically important dose response in lowering systolic or diastolic blood pressure at eplerenone doses of 50 mg to 400 mg daily. There did not appear to be any differences in the number of patients who withdrew due to adverse events or the number of patients with at least one adverse event in the eplerenone group compared to placebo. However, only three of the five included studies reported adverse events. Most of the included studies were of moderate quality, as we judged multiple domains as being at unclear risk in the 'Risk of bias' assessment. Eplerenone 50 to 200 mg/day lowers blood pressure in people with primary hypertension by 9.21 mmHg systolic and 4.18 mmHg diastolic compared to placebo, with no difference of effect between doses of 50 mg/day to 200 mg/day. A dose of 25 mg/day did not produce a statistically significant reduction in systolic or diastolic blood pressure and there is insufficient evidence for doses above 200 mg/day. There is currently no available evidence to determine the effect of eplerenone on clinically meaningful outcomes such as mortality or morbidity in hypertensive patients. The evidence available on side effects is insufficient and of low quality, which makes it impossible to draw conclusions about potential harm associated with eplerenone treatment in hypertensive patients.

Hypertension and vascular dementia in the elderly: the potential role of anti-hypertensive agents.

PubMed

Coca, Antonio

2013-09-01

Vascular dementia (VaD) - a severe form of vascular cognitive impairment - and cognitive decline are associated with hypertension and therefore it seems logical to consider that reducing BP with anti-hypertensive therapy may protect against the development/onset of cognitive function impairment or dementia. This narrative, non-systematic review discusses the available evidence on the potential correlation between the use of anti-hypertensive agents and the risk of VaD and cognitive decline. MEDLINE was searched for inclusion of relevant studies. No limitations in time were considered. A consensus on the potential effects of anti-hypertensive treatment in the reduction of VaD and associated cognitive decline has not been reached. A protective effect of anti-hypertensive agents has been observed in a number of studies although it is still unclear whether different classes of anti-hypertensive agents have a different effect on the development of VaD. The protective effect of anti-hypertensive agents appears to depend on the specific drug used - positive effects have been observed with calcium channel blockers (CCBs), such as lercanidipine and nitrendipine, the combination perindopril-indapamide and telmisartan.

Renal sympathetic denervation in the treatment of resistant hypertension.

PubMed

Sánchez-Álvarez, Catalina; González-Vélez, Miguel; Stilp, Erik; Ward, Charisse; Mena-Hurtado, Carlos

2014-12-01

Arterial hypertension (HTN) is a major health problem worldwide. Treatment-resistant hypertension (trHTN) is defined as the failure to achieve target blood pressure despite the concomitant use of maximally tolerated doses of three different antihypertensive medications, including a diuretic. trHTN is associated with considerable morbidity and mortality. Renal sympathetic denervation (RDn) is available and implemented abroad as a strategy for the treatment of trHTN and is currently under clinical investigation in the United States. Selective renal sympathectomy via an endovascular approach effectively decreases renal sympathetic nerve hyperactivity leading to a decrease in blood pressure. The Symplicity catheter, currently under investigation in the United States, is a 6-French compatible system advanced under fluoroscopic guidance via percutaneous access of the common femoral artery to the distal lumen of each of the main renal arteries. Radiofrequency (RF) energy is then applied to the endoluminal surface of the renal arteries via an electrode located at the tip of the catheter. Two clinical trials (Symplicity HTN 1 and Symplicity HTN 2) have shown the efficacy of RDn with a post-procedure decline of 27/17 mmHg at 12 months and 32/12 mmHg at 6 months, respectively, with few minor adverse events. Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study currently under way and will provide further insights about the safety and efficacy of renal denervation in patients with trHTN.

The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes.

PubMed

Mozaffari-Khosravi, H; Jalali-Khanabadi, B-A; Afkhami-Ardekani, M; Fatehi, F; Noori-Shadkam, M

2009-01-01

To compare the antihypertensive effectiveness of sour tea (ST; Hibiscus sabdariffa) with black tea (BT) infusion in diabetic patients, this double-blind randomized controlled trial was carried out. Sixty diabetic patients with mild hypertension, without taking antihypertensive or antihyperlipidaemic medicines, were recruited in the study. The patients were randomly allocated to the ST and BT groups and instructed to drink ST and BT infusions two times a day for 1 month. Their blood pressure (BP) was measured on days 0, 15 and 30 of the study. The mean of systolic BP (SBP) in the ST group decreased from 134.4+/-11.8 mm Hg at the beginning of the study to 112.7+/-5.7 mm Hg after 1 month (P-value <0.001), whereas this measure changed from 118.6+/-14.9 to 127.3+/-8.7 mm Hg (P-value=0.002) in the BT group during the same period. The intervention had no statistically significant effect on the mean of diastolic BP (DBP) in either the ST or BT group. The mean pulse pressure (PP) of the patients in the ST group decreased from 52.2+/-12.2 to 34.5+/-9.3 mm Hg (P-value <0.001) during the study, whereas in the BT group, it increased from 41.9+/-11.7 to 47.3+/-9.6 mm Hg (P-value=0.01). In conclusion, consuming ST infusion had positive effects on BP in type II diabetic patients with mild hypertension. This study supports the results of similar studies in which antihypertensive effects have been shown for ST.

Selective imidazoline agonist moxonidine plus the ACE inhibitor ramipril in hypertensive patients with impaired insulin sensitivity: partners in a successful MARRIAGE?

PubMed

Rayner, Brian

2004-03-01

Hypertension in combination with clinically overt diabetes mellitus is recognized as a particularly powerful combination of risk factors that greatly increases cardiovascular vulnerability. There is also evidence that presumed pre-diabetic conditions such as insulin resistance, hyperinsulinaemia and compensatory hyperglycaemia may amplify overall cardiovascular risk in patients with hypertension, especially when encountered as part of the condition known as metabolic syndrome X (Reaven's syndrome). The long-term benefits of antihypertensive therapy may be compromised if these drugs exert adverse effects on metabolic parameters such as insulin sensitivity, or if they promote a transition from pre-diabetes to overt diabetes. Class differences in the effects of antihypertensives on metabolic indices may therefore be an important consideration when choosing treatment for patients who exhibit these characteristics. Experience from clinical trials suggests that drugs that target the renin-angiotensin system may have metabolic advantages over drugs such as beta-blockers and diuretics, but this conclusion has not been proved definitively. Moxonidine, which selectively targets imidazoline type-1 receptors in the sympathetic vasomotor centres of the rostral-ventrolateral medulla, is an effective antihypertensive and has been reported to exert favourable metabolic effects in preclinical and clinical studies. The MARRIAGE study (Moxonidine And Ramipril Regarding Insulin And Glucose Evaluation) will extend these preliminary observations by comparing the effects of moxonidine and the ACE inhibitor ramipril--and the combination of both drugs--on metabolic and haemodynamic parameters in patients with hypertension and impaired fasting glycaemia. A description is provided of the design and conduct of MARRIAGE.

[Try to achieve quickly the blood pressure target in newly diagnosed hypertensive patients is safe and effective].

PubMed

Kichou, B; Henine, N; Kichou, L; Boubchir, M A; Ait Said, M A; Zatout, M; Hammouche, A; Mazeghrane, A; Madiou, A; Benbouabdellah, M

2018-06-01

To compare a so-called an "accelerated" antihypertensive strategy to a "standard" strategy, in terms of blood pressure control rates and adverse events. Prospective open-label randomized controlled trial, which included consecutive hypertensive patients, newly diagnosed, 40 to 70 years old, with no prior antihypertensive treatment. Hypertension was diagnosed if office blood pressure was≥140/90mmHg, confirmed by an increase of Home or a daytime ambulatory blood pressure. The patients were randomly assigned according to 1:1 ratio to an "accelerated" strategy or to a "standard" strategy. The primary end-point was the rate of blood pressure control at 12weeks. The secondary end-point was the rate of adverse events (a safety end-point). We recruited 268 patients (132 in the "accelerated" strategy group), with a mean age of 55 years and 62% of men. The mean office blood pressure at baseline was 168/95mmHg. The clinical characteristics were on average similar between the 2 treatment groups. At 12 weeks, the rates of blood pressure control were 63.6% in the "accelerated" strategy and 38.2% in the "standard" strategy (P<0.001). There was no significantly difference between the rates of adverse events in the 2 strategies (6.06% versus 5.14%; P=0.8). The "accelerated" antihypertensive strategy was more effective than a standard one, in terms of blood pressure control, without an increase in adverse events rate. This could translate into a future cardiovascular events reduction. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Class III antiarrhythmic agents in cardiac failure: lessons from clinical trials with a focus on the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA).

PubMed

Doval, H C

1999-11-04

The results of previous clinical trials, in a variety of clinical settings, showed that class I agents may consistently increase mortality in sharp contrast to the effects of beta blockers. Attention has therefore shifted to class III compounds for potential beneficial effects on long-term mortality among patients with underlying cardiac disease. Clinical trials with d-sotalol, the dextro isomer (devoid of beta blockade) of sotalol, showed increased mortality in patients with low ejection fraction after myocardial infarction and in those with heart failure; whereas in the case of dofetilide, the impact on mortality was neutral. Because of the complex effects of its actions as an alpha-adrenergic blocker and a class III agent, the impact on mortality of amiodarone in patients with heart failure is of particular interest. A meta-analysis of 13 clinical trials revealed significant reductions in all-cause and cardiac mortality among patients with heart failure or previous myocardial infarction. Among these were 5 controlled clinical trials that investigated the effects of amiodarone on mortality among patients with heart failure. None of these trials was large relative to the beta-blocker trials in the postinfarction patients. However, the larger 2 of the 5 amiodarone trials produced discordant effects on mortality, neutral in one and significantly positive in the other. Some of the differences may be accounted for by the differences in eligibility criteria and baseline characteristics. Future trials that may be undertaken to resolve the discrepancies may need to allow for the newer findings on the effects of concomitant beta blockers, implantable devices, and possibly, spironolactone. All these modalities of treatment have been shown in controlled clinical trials to augment survival in patients with impaired ventricular function or manifest heart failure. Additional trials, some of which are currently in progress, compare amiodarone with implantable devices and other therapeutic interventions, and should help to clarify the optimal management strategy for patients with underlying heart failure.

Characteristics and Factors Associated With Antihypertensive Medication Use in Patients Attending Peruvian Health Facilities

PubMed Central

Mejia, Christian R; Failoc-Rojas, Virgilio E; Cervantes, Carmen; Aspajo, Antonio J; Leandro, Jesus Galileo; Cordova-De La Cruz, Jhomar; Charri, Julio C; García-Auqui, Kevin E; Coronel-Chucos, Lelis Gabriela; Justo-Pinto, Luz Delia; Mamani-Apaza, Marisol Stefanie; Paz-Campos, Neil Arón; Correa, Ricardo

2017-01-01

Introduction  Hypertension is a very common disease worldwide, and medication is needed to prevent its short-term and long-term complications. Our objective was to determine the characteristics and factors associated with antihypertensive medication use in patients attending Peruvian health facilities. Materials & Methods We performed a multicenter, cross-sectional study with secondary data. We obtained self-reported antihypertensive medication from patients attending health facilities in 10 departments of Peru. We looked for associations of the antihypertensive treatment according to sociopathological factors and obtained p values using generalized linear models. Results Of the 894 patients with hypertension, 61% (547) were women and 60% (503) were on antihypertensive treatment, of which 82% (389) had monotherapy and 52% (258) had recently taken their medication. Antihypertensive treatment was positively correlated with the patient's age (adjusted prevalence ratio [aPR]: 1.01; 95% confidence interval [CI]: 1.007 to 1.017; p value < 0.001), diabetes (aPR: 1.31; 95% CI: 1.11 to 1.55; p value = 0.001) and cardiovascular disease (aPR: 1.38; 95% CI: 1.26 to 1.51; p value < 0.001). Conversely, the frequency of antihypertensive treatment decreases with physical activity (aPR: 0.80; 95% CI: 0.70 to 0.92; p value = 0.001). Conclusion Patients who have comorbidities and advanced age are more likely to be on antihypertensive treatment. In contrast, patients with increased physical activity have a lower frequency of antihypertensive treatment. It is important to consider these factors for future preventive programs and to improve therapeutic compliance. PMID:28331773

Use of antihypertensive medications and diagnostic tests among privately insured adolescents and young adults with primary versus secondary hypertension.

PubMed

Yoon, Esther Y; Cohn, Lisa; Freed, Gary; Rocchini, Albert; Kershaw, David; Ascione, Frank; Clark, Sarah

2014-07-01

To compare the use of antihypertensive medications and diagnostic tests among adolescents and young adults with primary versus secondary hypertension. We conducted retrospective cohort analysis of claims data for adolescents and young adults (12-21 years of age) with ≥3 years of insurance coverage (≥11 months/year) in a large private managed care plan during 2003-2009 with diagnosis of primary hypertension or secondary hypertension. We examined their use of antihypertensive medications and identified demographic characteristics and the presence of obesity-related comorbidities. For the subset receiving antihypertensive medications, we examined their diagnostic test use (echocardiograms, renal ultrasounds, and electrocardiograms). The study sample included 1,232 adolescents and young adults; 84% had primary hypertension and 16% had secondary hypertension. The overall prevalence rate of hypertension was 2.6%. One quarter (28%) with primary hypertension had one or more antihypertensive medications, whereas 65% with secondary hypertension had one or more antihypertensive medications. Leading prescribers of antihypertensives for subjects with primary hypertension were primary care physicians (80%), whereas antihypertensive medications were equally prescribed by primary care physicians (43%) and sub-specialists (37%) for subjects with secondary hypertension. The predominant hypertension diagnosis among adolescents and young adults is primary hypertension. Antihypertensive medication use was higher among those with secondary hypertension compared with those with primary hypertension. Further study is needed to determine treatment effectiveness and patient outcomes associated with differential treatment patterns used for adolescents and young adults with primary versus secondary hypertension. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Characteristics and Factors Associated With Antihypertensive Medication Use in Patients Attending Peruvian Health Facilities.

PubMed

Mejia, Christian R; Failoc-Rojas, Virgilio E; So, Edison; Cervantes, Carmen; Aspajo, Antonio J; Leandro, Jesus Galileo; Cordova-De La Cruz, Jhomar; Charri, Julio C; García-Auqui, Kevin E; Coronel-Chucos, Lelis Gabriela; Justo-Pinto, Luz Delia; Mamani-Apaza, Marisol Stefanie; Paz-Campos, Neil Arón; Correa, Ricardo

2017-02-03

Hypertension is a very common disease worldwide, and medication is needed to prevent its short-term and long-term complications. Our objective was to determine the characteristics and factors associated with antihypertensive medication use in patients attending Peruvian health facilities. We performed a multicenter, cross-sectional study with secondary data. We obtained self-reported antihypertensive medication from patients attending health facilities in 10 departments of Peru. We looked for associations of the antihypertensive treatment according to sociopathological factors and obtained p values using generalized linear models. Of the 894 patients with hypertension, 61% (547) were women and 60% (503) were on antihypertensive treatment, of which 82% (389) had monotherapy and 52% (258) had recently taken their medication. Antihypertensive treatment was positively correlated with the patient's age (adjusted prevalence ratio [aPR]: 1.01; 95% confidence interval [CI]: 1.007 to 1.017; p value < 0.001), diabetes (aPR: 1.31; 95% CI: 1.11 to 1.55; p value = 0.001) and cardiovascular disease (aPR: 1.38; 95% CI: 1.26 to 1.51; p value < 0.001). Conversely, the frequency of antihypertensive treatment decreases with physical activity (aPR: 0.80; 95% CI: 0.70 to 0.92; p value = 0.001). Patients who have comorbidities and advanced age are more likely to be on antihypertensive treatment. In contrast, patients with increased physical activity have a lower frequency of antihypertensive treatment. It is important to consider these factors for future preventive programs and to improve therapeutic compliance.

Relationship between Sponsorship and Failure Rate of Dental Implants: A Systematic Approach

PubMed Central

Popelut, Antoine; Valet, Fabien; Fromentin, Olivier; Thomas, Aurélie; Bouchard, Philippe

2010-01-01

Background The number of dental implant treatments increases annually. Dental implants are manufactured by competing companies. Systematic reviews and meta-analysis have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. So far, the impact of industry sponsorship on the outcomes and conclusions of dental implant clinical trials has never been explored. The aim of the present study was to examine financial sponsorship of dental implant trials, and to evaluate whether research funding sources may affect the annual failure rate. Methods and Findings A systematic approach was used to identify systematic reviews published between January 1993 and December 2008 that specifically deal with the length of survival of dental implants. Primary articles were extracted from these reviews. The failure rate of the dental implants included in the trials was calculated. Data on publication year, Impact Factor, prosthetic design, periodontal status reporting, number of dental implants included in the trials, methodological quality of the studies, presence of a statistical advisor, and financial sponsorship were extracted by two independent reviewers (kappa  = 0.90; CI95% [0.77–1.00]). Univariate quasi-Poisson regression models and multivariate analysis were used to identify variables that were significantly associated with failure rates. Five systematic reviews were identified from which 41 analyzable trials were extracted. The mean annual failure rate estimate was 1.09%.(CI95% [0.84–1.42]). The funding source was not reported in 63% of the trials (26/41). Sixty-six percent of the trials were considered as having a risk of bias (27/41). Given study age, both industry associated (OR = 0.21; CI95% [0.12–0.38]) and unknown funding source trials (OR = 0.33; (CI95% [0.21–0.51]) had a lower annual failure rates compared with non-industry associated trials. A conflict of interest statement was disclosed in 2 trials. Conclusions When controlling for other factors, the probability of annual failure for industry associated trials is significantly lower compared with non-industry associated trials. This bias may have significant implications on tooth extraction decision making, research on tooth preservation, and governmental health care policies. PMID:20422000

Reassessing Phase II Heart Failure Clinical Trials: Consensus Recommendations

PubMed Central

Butler, Javed; Hamo, Carine E.; Udelson, James E.; O’Connor, Christopher; Sabbah, Hani N.; Metra, Marco; Shah, Sanjiv J.; Kitzman, Dalane W.; Teerlink, John; Bernstein, Harold S.; Brooks, Gabriel; Depre, Christophe; DeSouza, Mary M.; Dinh, Wilfried; Donovan, Mark; Frische-Danielson, Regina; Frost, Robert J.; Garza, Dahlia; Gohring, Udo-Michael; Hellawell, Jennifer; Hsia, Judith; Ishihara, Shiro; Kay-Mugford, Patricia; Koglin, Joerg; Kozinn, Marc; Larson, Christopher J.; Mayo, Martha; Gan, Li-Ming; Mugnier, Pierrre; Mushonga, Sekayi; Roessig, Lothar; Russo, Cesare; Salsali, Afshin; Satler, Carol; Shi, Victor; Ticho, Barry; van der Laan, Michael; Yancy, Clyde; Stockbridge, Norman; Gheorghiade, Mihai

2017-01-01

The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue regarding the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17th 2016 represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions. PMID:28356300

Contralateral Delay Activity Tracks Fluctuations in Working Memory Performance.

PubMed

Adam, Kirsten C S; Robison, Matthew K; Vogel, Edward K

2018-01-08

Neural measures of working memory storage, such as the contralateral delay activity (CDA), are powerful tools in working memory research. CDA amplitude is sensitive to working memory load, reaches an asymptote at known behavioral limits, and predicts individual differences in capacity. An open question, however, is whether neural measures of load also track trial-by-trial fluctuations in performance. Here, we used a whole-report working memory task to test the relationship between CDA amplitude and working memory performance. If working memory failures are due to decision-based errors and retrieval failures, CDA amplitude would not differentiate good and poor performance trials when load is held constant. If failures arise during storage, then CDA amplitude should track both working memory load and trial-by-trial performance. As expected, CDA amplitude tracked load (Experiment 1), reaching an asymptote at three items. In Experiment 2, we tracked fluctuations in trial-by-trial performance. CDA amplitude was larger (more negative) for high-performance trials compared with low-performance trials, suggesting that fluctuations in performance were related to the successful storage of items. During working memory failures, participants oriented their attention to the correct side of the screen (lateralized P1) and maintained covert attention to the correct side during the delay period (lateralized alpha power suppression). Despite the preservation of attentional orienting, we found impairments consistent with an executive attention theory of individual differences in working memory capacity; fluctuations in executive control (indexed by pretrial frontal theta power) may be to blame for storage failures.

Inpatient falls in older adults: a cohort study of antihypertensive prescribing pre- and post-fall.

PubMed

Omer, H M R B; Hodson, J; Pontefract, S K; Martin, U

2018-02-23

Falls are common during hospital admissions and may occur more frequently in patients who are taking antihypertensive medications, particularly in the context of normal to low blood pressure. The review and adjustment of these medications is an essential aspect of the post-fall assessment and should take place as soon as possible after the fall. Our aim was to investigate whether appropriate post-fall adjustments of antihypertensive medications are routinely made in a large National Health Service (NHS) Trust. Inpatient records over an eight-month period were captured from an electronic prescribing system to identify older adults (≥80 years old) with normal/low blood pressures (< 140 mmHg systolic) who had a documented inpatient fall as these patients were considered to be at high risk of further falls. Prescribed antihypertensive medication on admission was then compared with the post-fall (within 24 h after the fall) and discharge prescriptions. A total of 146 patients were included in the analysis. Of those, 120 patients (82%) were taking the same number of antihypertensive medications in the 24 h after the fall as they were before; only 19 patients (13%) had a reduction in the number of medications and seven patients (5%) had an increase in medications during that period. Only 9% of the antihypertensive classes assessed were either stopped or reduced in dose immediately post-fall. In addition, 11 new antihypertensives were prescribed at this time. At discharge, half of the patients (n = 73) remained on the same number of antihypertensive medication as on admission, 51 patients (35%) were on fewer antihypertensives and 22 (15%) were on more. Additionally, no changes were made to individual antihypertensives in 49% of prescriptions; 34% were stopped or reduced in dose but 38 new agents were started by the time of discharge. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers (ACEi/ARB) were the class of medications most commonly stopped or reduced (51%). Antihypertensive prescriptions are frequently unchanged after an inpatient fall. Routine medication review needs to be part of post-fall assessments in hospital to reduce the risk of further falls.

Modelling of Safety Instrumented Systems by using Bernoulli trials: towards the notion of odds on for SIS failures analysis

NASA Astrophysics Data System (ADS)

Cauffriez, Laurent

2017-01-01

This paper deals with the modeling of a random failures process of a Safety Instrumented System (SIS). It aims to identify the expected number of failures for a SIS during its lifecycle. Indeed, the fact that the SIS is a system being tested periodically gives the idea to apply Bernoulli trials to characterize the random failure process of a SIS and thus to verify if the PFD (Probability of Failing Dangerously) experimentally obtained agrees with the theoretical one. Moreover, the notion of "odds on" found in Bernoulli theory allows engineers and scientists determining easily the ratio between “outcomes with success: failure of SIS” and “outcomes with unsuccess: no failure of SIS” and to confirm that SIS failures occur sporadically. A Stochastic P-temporised Petri net is proposed and serves as a reference model for describing the failure process of a 1oo1 SIS architecture. Simulations of this stochastic Petri net demonstrate that, during its lifecycle, the SIS is rarely in a state in which it cannot perform its mission. Experimental results are compared to Bernoulli trials in order to validate the powerfulness of Bernoulli trials for the modeling of the failures process of a SIS. The determination of the expected number of failures for a SIS during its lifecycle opens interesting research perspectives for engineers and scientists by completing the notion of PFD.

Choice of generic antihypertensive drugs for the primary prevention of cardiovascular disease--a cost-effectiveness analysis.

PubMed

Wisløff, Torbjørn; Selmer, Randi M; Halvorsen, Sigrun; Fretheim, Atle; Norheim, Ole F; Kristiansen, Ivar Sønbø

2012-04-04

Hypertension is one of the leading causes of cardiovascular disease (CVD). A range of antihypertensive drugs exists, and their prices vary widely mainly due to patent rights. The objective of this study was to explore the cost-effectiveness of different generic antihypertensive drugs as first, second and third choice for primary prevention of cardiovascular disease. We used the Norwegian Cardiovascular Disease model (NorCaD) to simulate the cardiovascular life of patients from hypertension without symptoms until they were all dead or 100 years old. The risk of CVD events and costs were based on recent Norwegian sources. In single-drug treatment, all antihypertensives are cost-effective compared to no drug treatment. In the base-case analysis, the first, second and third choice of antihypertensive were calcium channel blocker, thiazide and angiotensin-converting enzyme inhibitor. However the sensitivity and scenario analyses indicated considerable uncertainty in that angiotensin receptor blockers as well as, angiotensin-converting enzyme inhibitors, beta blockers and thiazides could be the most cost-effective antihypertensive drugs. Generic antihypertensives are cost-effective in a wide range of risk groups. There is considerable uncertainty, however, regarding which drug is the most cost-effective.

Interactions between antihypertensive drugs and food.

PubMed

Jáuregui-Garrido, B; Jáuregui-Lobera, I

2012-01-01

A drug interaction is defined as any alteration, pharmacokinetics and/or pharmacodynamics, produced by different substances, other drug treatments, dietary factors and habits such as drinking and smoking. These interactions can affect the antihypertensive drugs, altering their therapeutic efficacy and causing toxic effects. The aim of this study was to conduct a review of available data about interactions between antihypertensive agents and food. The purpose of this review was to report an update of main findings with respect to the interactions between food and antihypertensive drugs by way of a search conducted in PubMed, which yielded a total of 236 articles initially. After excluding different articles, which were not focusing on the specific objective, the main results refer to interactions between antihypertensive drugs and food (in general) as well as between antihypertensive agents and grapefruit juice. Food may affect the bioavailability of antihypertensive drugs and this should be carefully considered. Advising patients to remove the grapefruit juice from their diet when treatment with these drugs seems to be the best recommendation. Given these interactions and the associated potential adverse effects the anamnesis must include detailed information about the specific eating habits of the patients.

Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial.

PubMed

Bakris, George L; Sarafidis, Pantelis A; Weir, Matthew R; Dahlöf, Björn; Pitt, Bertram; Jamerson, Kenneth; Velazquez, Eric J; Staikos-Byrne, Linda; Kelly, Roxzana Y; Shi, Victor; Chiang, Yann-Tong; Weber, Michael A

2010-04-03

The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease. ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1.73 m(2) or need for dialysis). Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00170950. The trial was terminated early (mean follow-up 2.9 years [SD 0.4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. At trial completion, vital status was not known for 143 (1%) patients who were lost to follow-up (benazepril plus amlodipine, n=70; benazepril plus hydrochlorothiazide, n=73). All randomised patients were included in the ITT analysis. There were 113 (2.0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3.7%) in the benazepril plus hydrochlorothiazide group (HR 0.52, 0.41-0.65, p<0.0001). The most frequent adverse event in patients with chronic kidney disease was peripheral oedema (benazepril plus amlodipine, 189 of 561, 33.7%; benazepril plus hydrochlorothiazide, 85 of 532, 16.0%). In patients with chronic kidney disease, angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalaemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group. Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent. Novartis. Copyright 2010 Elsevier Ltd. All rights reserved.

Clinical trials update from the European Society of Cardiology meeting 2014: PARADIGM-HF, CONFIRM-HF, SIGNIFY, atrial fibrillation, beta-blockers and heart failure, and vagal stimulation in heart failure.

PubMed

Clark, Andrew L; Pellicori, Pierpaolo

2014-12-01

This article provides an overview of trials relevant to the pathophysiology, prevention, and treatment of heart failure, presented at the European Society of Cardiology meeting held in Barcelona in autumn 2014. Trials reported here include PARADIGM-HF (LCZ696 versus enalapril in heart failure), CONFIRM-HF (treatment of iron deficiency in heart failure), and SIGNIFY (ivabradine in patients with stable coronary artery disease). In addition, we discuss recent developments in the treatment of atrial fibrillation and the lack of benefit with the use of beta-blockers in these patients. Finally, the article describes recent advances in the use of vagal stimulation in patients with heart failure. © 2014 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. © 2014 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Short-term Risk of Serious Fall Injuries in Older Adults Initiating and Intensifying Treatment with Antihypertensive Medication

PubMed Central

Shimbo, Daichi; Bowling, C. Barrett; Levitan, Emily B.; Deng, Luqin; Sim, John J.; Huang, Lei; Reynolds, Kristi; Muntner, Paul

2016-01-01

Background Antihypertensive medication use has been associated with an increased risk of falls in some but not all studies. Few data are available on the short-term risk of falls following antihypertensive medication initiation and intensification. Methods and Results We examined the association between initiating and intensifying antihypertensive medication and serious fall injuries in a case-crossover study of 90,127 Medicare beneficiaries who were ≥65 years old and had a serious fall injury between July 1, 2007 and December 31, 2012, based on emergency department and inpatient claims. Antihypertensive medication initiation was defined by a prescription fill with no fills in the prior year. Intensification was defined by the addition of a new antihypertensive class, and, separately, titration by the addition of a new class or increase in dosage of a current class. Exposures were ascertained for the 15 days before the fall (case period) and six 15-day earlier periods (control periods). Overall, 272, 1508, and 3113 Medicare beneficiaries initiated, added a new class of antihypertensive medication or titrated therapy, respectively, within 15 days of their serious fall injury. The odds for a serious fall injury was increased during the 15 days following antihypertensive medication initiation [odds ratio, OR, 1.36 (95% CI 1.19, 1.55)], adding a new class [OR 1.16 (95% CI 1.10, 1.23)], and titration [OR 1.13 (95% CI 1.08, 1.18)]. These associations were attenuated beyond 15 days. Conclusions Antihypertensive medication initiation and intensification was associated with a short-term, but not long-term, increased risk of serious fall injuries among older adults. PMID:27166208

Short-Term Risk of Serious Fall Injuries in Older Adults Initiating and Intensifying Treatment With Antihypertensive Medication.

PubMed

Shimbo, Daichi; Barrett Bowling, C; Levitan, Emily B; Deng, Luqin; Sim, John J; Huang, Lei; Reynolds, Kristi; Muntner, Paul

2016-05-01

Antihypertensive medication use has been associated with an increased risk of falls in some but not all studies. Few data are available on the short-term risk of falls after antihypertensive medication initiation and intensification. We examined the association between initiating and intensifying antihypertensive medication and serious fall injuries in a case-crossover study of 90 127 Medicare beneficiaries who were ≥65 years old and had a serious fall injury between July 1, 2007, and December 31, 2012, based on emergency department and inpatient claims. Antihypertensive medication initiation was defined by a prescription fill with no fills in the previous year. Intensification was defined by the addition of a new antihypertensive class, and separately, titration by the addition of a new class or increase in dosage of a current class. Exposures were ascertained for the 15 days before the fall (case period) and six 15-day earlier periods (control periods). Overall, 272, 1508, and 3113 Medicare beneficiaries initiated, added a new class of antihypertensive medication or titrated therapy within 15 days of their serious fall injury. The odds for a serious fall injury was increased during the 15 days after antihypertensive medication initiation (odds ratio, 1.36 [95% confidence interval, 1.19-1.55]), adding a new class (odds ratio, 1.16 [95% confidence interval, 1.10-1.23]), and titration [odds ratio, 1.13 [95% confidence interval, 1.08-1.18]). These associations were attenuated beyond 15 days. Antihypertensive medication initiation and intensification was associated with a short-term, but not long-term, increased risk of serious fall injuries among older adults. © 2016 American Heart Association, Inc.

Persistence with Antihypertensive Drugs in Patients with Hypertension and Dementia in Germany.

PubMed

Jacob, Louis; Adam-Schnepf, Leonie; Kostev, Karel

2017-01-01

Hypertension, a chronic disease resulting from aging and its related physiopathological dysregulations, is often associated with dementia. The goal was to analyze the persistence with antihypertensive drugs in patients affected by both hypertension and dementia in Germany. This study included hypertension patients who were initially treated with antihypertensive drugs in 1,262 general practices in Germany between January 2013 and December 2015 (index date). Patients with hypertension and comorbid dementia were matched (1 : 1) to patients without dementia by age, gender, type of residence (nursing home versus home-care setting), physician, and initial antihypertensive therapy, using a propensity score method. The primary outcome was the rate of patients without treatment discontinuation with antihypertensive drugs in cases and controls in the 12 months following the index date. Cox regressions were used to determine the impact of dementia on persistence with antihypertensive treatment. This study included 2,191 patients with hypertension and comorbid dementia and 2,191 patients with hypertension but without dementia. The mean age was 79.3 years (SD = 10.3 years) in both groups. Twelve months after initiation of antihypertensive therapy, 73.5% of cases and 69.5% of controls were persistent (p < 0.001). Dementia was associated with a significant decrease in the risk of non-persistence with antihypertensive drugs in the entire population (HR = 0.86, 95% CI: 0.79-0.93). This finding was corroborated in five different subgroups (age ≤60 years, age 61-70 years, men, women, and patients living in home-care settings). Dementia was found to be a protective factor for persistence with antihypertensive drugs in Germany.

Maternal Antihypertensive Medication Use and Congenital Heart Defects: Updated Results From the National Birth Defects Prevention Study.

PubMed

Fisher, Sarah C; Van Zutphen, Alissa R; Werler, Martha M; Lin, Angela E; Romitti, Paul A; Druschel, Charlotte M; Browne, Marilyn L

2017-05-01

Previous NBDPS (National Birth Defects Prevention Study) findings from 1997 to 2003 suggested that maternal antihypertensive use was associated with congenital heart defects (CHDs). We re-examined associations between specific antihypertensive medication classes and specific CHDs with additional NBDPS data from 2004 to 2011. After excluding mothers missing hypertension information or who reported pregestational diabetes mellitus, a multiple birth, or antihypertensive use but no hypertension, we compared self-reported maternal exposure data on 10 625 CHD cases and 11 137 nonmalformed controls. We calculated adjusted odds ratios [95% confidence intervals] to estimate the risk of specific CHDs associated with antihypertensive use during the month before conception through the third month of pregnancy, controlling for maternal age, race/ethnicity, body mass index, first trimester cigarette smoking, and NBDPS site. Overall, 164 (1.5%) case mothers and 102 (0.9%) control mothers reported early pregnancy antihypertensive use for their hypertension. We observed increased risk of 4 CHD phenotypes, regardless of antihypertensive medication class reported: coarctation of the aorta (2.50 [1.52-4.11]), pulmonary valve stenosis (2.19 [1.44-3.34]), perimembranous ventricular septal defect (1.90 [1.09-3.31]), and secundum atrial septal defect (1.94 [1.36-2.79]). The associations for these phenotypes were statistically significant for mothers who reported β-blocker use or renin-angiotensin system blocker use; estimates for other antihypertensive medication classes were generally based on fewer exposed cases and were less stable but remained elevated. Our results support and expand on earlier NBDPS findings that antihypertensive medication use may be associated with increased risk of specific CHDs, although we cannot completely rule out confounding by underlying disease characteristics. © 2017 American Heart Association, Inc.

Assessing the Eligibility Criteria in Phase III Randomized Controlled Trials of Drug Therapy in Heart Failure With Preserved Ejection Fraction: The Critical Play-Off Between a "Pure" Patient Phenotype and the Generalizability of Trial Findings.

PubMed

Patel, Hitesh C; Hayward, Carl; Dungu, Jason N; Papadopoulou, Sofia; Saidmeerasah, Abdel; Ray, Robin; Di Mario, Carlo; Shanmugam, Nesan; Cowie, Martin R; Anderson, Lisa J

2017-07-01

To investigate the effect of the different eligibility criteria used by phase III clinical studies in heart failure with preserved ejection fraction (HFpEF) on patient selection, phenotype, and survival. We applied the key eligibility criteria of 7 phase III HFpEF studies (Digitalis Investigation Group Ancillary, Candesartan in Patients With Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction, Perindopril in Elderly People With Chronic Heart Failure, Irbesartan in Heart Failure With Preserved Systolic Function, Japanese Diastolic Heart Failure, Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist, and Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF; ongoing]) to a typical and well-characterized HFpEF population (n = 557) seen in modern European cardiological practice. Follow-up was available for a minimum of 24 months in each patient. Increasing the number of study eligibility criteria identifies a progressively smaller group of patients from real-life practice suitable for recruitment into clinical trials; using the J-DHF criteria, 81% of our clinic patients would have been eligible, whereas the PARAGON-HF criteria significantly reduced this proportion to 32%. The patients identified from our clinical population had similar mortality rates using the different criteria, which were consistently higher than those reported in the actual clinic trials. Trial eligibility criteria have become stricter with time, which reduces the number of eligible patients, affecting both generalizability of any findings and feasibility of completing an adequately powered trial. We could not find evidence that the additional criteria used in more recent randomized trials in HFpEF have identified patients at higher risk of all-cause mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of beta-blocker therapy on mortality in patients with heart failure. A systematic overview of randomized controlled trials.

PubMed

Doughty, R N; Rodgers, A; Sharpe, N; MacMahon, S

1997-04-01

Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects. Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2P = 0.0035), representing an absolute reduction in mean annual mortality from 9.7% to 7.5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were non-significantly greater (2P = 0.09) than those of standard agents (18% reduction SD 15), principally metoprolol. Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.

Effect of Preoperative Low Maximal Flow Rate on Postoperative Voiding Trials after the Midurethral Sling Procedure in Women with Stress Urinary Incontinence.

PubMed

Chae, Ji Y; Bae, Jae H; Lee, Jeong G; Park, Hong S; Moon, Du G; Oh, Mi M

2017-06-02

To evaluate the effects of preoperative low maximal flow rate (Qmax) on voiding trials after the midurethral sling (MUS) procedure in women with stress urinary incontinence (SUI). One hundred and sixty-eight women who underwent MUS procedure were enrolled. Preoperative free uroflowmetry was performed and patients were divided by Qmax. Low Qmax was defined as a Qmax under 15 mL/sec with voided volume at least 150 mL. Surgical results, failure of voiding trial, and postoperative uroflowmetry parameters were compared between the groups. Failure of voiding trial was defined by a PVR more than 100 mL on postoperative uroflowmetry. At the discharge day, there were 42 cases showing failure of voiding trial and 33 cases requiring CIC, but only one patient showed failure of voiding trial at 12 months postoperatively. Overall, 48 patients had preoperative low Qmax. Low Qmax group showed lower Qmax in all of postoperative uroflowmetry, but there were no significant differences in the rate of postoperative voiding trial failure or CIC. The low Qmax group was then divided into two groups according to the preoperative detrusor pressure at Qmax over and under 20 cmH 2 O in pressure flow study. Comparing the two groups, no significant differences were observed in the cure rate, voiding trial failure or CIC. Our results suggest that women with preoperative low Qmax experienced no definite unfavorable voiding problem from the MUS procedure compared to those with normal voiding function. MUS procedure may be regarded as a safe and successful procedure in SUI women with low Qmax. © 2017 John Wiley & Sons Australia, Ltd.

Association of Severe Obstructive Sleep Apnea and Elevated Blood Pressure Despite Antihypertensive Medication Use

PubMed Central

Walia, Harneet K.; Li, Hong; Rueschman, Michael; Bhatt, Deepak L.; Patel, Sanjay R.; Quan, Stuart F.; Gottlieb, Daniel J.; Punjabi, Naresh M.; Redline, Susan; Mehra, Reena

2014-01-01

Rationale: We hypothesized that untreated severe obstructive sleep apnea (OSA) is associated with elevated ambulatory blood pressure (BP) in subjects with high cardiovascular disease (CVD) risk despite medical management. Methods: Data from the baseline examination of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a 4-site randomized controlled trial were analyzed. Individuals with moderate-severe OSA (apnea hypopnea index, AHI = 15-50) and cardiovascular risk were recruited from cardiology practices. Those with hypertension were included. Intensive antihypertensive regimen (IAR) was defined as ≥ 3 antihypertensives including a diuretic. Definitions were: controlled BP (BP < 130/80), uncontrolled elevated BP (BP ≥ 130/80 not on IAR) and resistant elevated BP (BP ≥ 130/80 mm Hg despite IAR). Associations of untreated severe OSA (AHI ≥ 30) and uncontrolled and resistant elevated BP were evaluated using logistic regression analyses adjusted for age, sex, race, body mass index, smoking status, diabetes, and CVD. Results: Among the 284 participants (mean age 63.1 ± 7.2 years, 23.6% with severe OSA), 61.6% had controlled BP, 28.5% had uncontrolled elevated BP, and 9.9% had resistant elevated BP. Among participants prescribed IAR, resistant elevated BP was more prevalent in those with severe compared to moderate OSA (58.3% vs. 28.6%, p = 0.01). Participants with severe OSA had a 4-fold higher adjusted odds of resistant elevated BP (OR 4.1, 95% CI: 1.7-10.2), a finding not reproduced in the absence of IAR use. Conclusions: Among patients with increased cardiovascular risk and moderate to severe OSA, untreated severe compared to moderate OSA was associated with elevated BP despite IAR suggesting untreated severe OSA contributes to poor BP control despite aggressive medication use. Commentary: A commentary on this article appears in this issue on page 845. Citation: Walia HK, Li H, Rueschman M, Bhatt DL, Patel SR, Quan SF, Gottlieb DJ, Punjabi NM, Redline S, Mehra R. Association of severe obstructive sleep apnea and elevated blood pressure despite antihypertensive medication use. J Clin Sleep Med 2014;10(8):835-843. PMID:25126027

More hypotension in patients taking antihypertensives preoperatively during shoulder surgery in the beach chair position.

PubMed

Trentman, Terrence L; Fassett, Sharon L; Thomas, Justin K; Noble, Brie N; Renfree, Kevin J; Hattrup, Steven J

2011-11-01

Hypotension is common in patients undergoing surgery in the sitting position under general anesthesia, and the risk may be exacerbated by the use of antihypertensive drugs taken preoperatively. The purpose of this study was to compare hypotensive episodes in patients taking antihypertensive medications with normotensive patients during shoulder surgery in the beach chair position. Medical records of all patients undergoing shoulder arthroscopy during a 44-month period were reviewed retrospectively. The primary endpoint was the number of moderate hypotensive episodes (systolic blood pressure ≤ 85 mmHg) during the intraoperative period. Secondary endpoints included the frequency of vasopressor administration, total dose of vasopressors, and fluid administered. Values are expressed as mean (standard deviation). Of 384 patients who underwent shoulder surgery, 185 patients were taking no antihypertensive medication, and 199 were on at least one antihypertensive drug. The antihypertensive medication group had more intraoperative hypotensive episodes [1.7 (2.2) vs 1.2 (1.8); P = 0.01] and vasopressor administrations. Total dose of vasopressors and volume of fluids administered were similar between groups. The timing of the administration of angiotensin-converting enzyme inhibitors and of angiotensin receptor antagonists (≤ 10 hr vs > 10 hr before surgery) had no impact on intraoperative hypotension. Preoperative use of antihypertensive medication was associated with an increased incidence of intraoperative hypotension. Compared with normotensive patients, patients taking antihypertensive drugs preoperatively are expected to require vasopressors more often to maintain normal blood pressure.

The Prevalence of Japanese Outpatients with Hypertension Who Meet the Definition of Treatment Resistant Hypertension and Are Eligible for Enrolment in Clinical Trials of Endovascular Ultrasound Renal Denervation.

PubMed

Okamura, Keisuke; Shirai, Kazuyuki; Okuda, Tetsu; Urata, Hidenori

2018-01-01

Objective A clinical trial (REQUIRE) was started to investigate the use of an ultrasound renal denervation system in the treatment of resistant hypertension (RHT). We analyzed the prevalence of patients who were eligible for inclusion in this cross-sectional study at the time of screening. Methods Nine-hundred ninety-nine consecutive hypertension (HT) patients who were treated in our hospital as outpatients were classified into the following categories: patients treated with at least 3 types of antihypertensive drugs including diuretic agents who were eligible for enrolment in SYMPLICITY HTN-Japan (SH-J) with an office systolic blood pressure (SBP) of ≥160 mmHg, who were ≤80 years of age, and an estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73 m 2 (RHT-S); and patients who were treated similar medications and who were eligible for enrolment in REQUIRE, with an SBP of ≥150 mmHg, ≤75 years of age, and an eGFR of ≥40 mL/min/1.73 m 2 (RHT-R). We investigated the proportion of patients in each category. We also investigated HT patients (1,423 cases) who were enrolled in the Chikushi Anti-Hypertension Trial (CHAT), a research network that includes general practitioners. Results Eleven patients (1.1%) with RHT-S and 18 patients (1.8%) with RHT-R were identified. After the exclusion of patients with secondary HT and a diastolic blood pressure (DBP) of <90 mmHg (applied in REQUIRE), 5 patients (0.5%) with RHT-S and 4 patients (0.4%) with RHT-R remained. In the analysis of the CHAT study, only 2 (0.1%) patients with RHT-R remained. Conclusion The number of eligible patients in the REQUIRE trial was decreased, largely due to the strict age restriction and the new DBP limitation. The prevalence of eligible patients in REQUIRE was estimated to be approximately 0.5 to 0.8 times that in SH-J. Since patient enrollment will be difficult, drastic measures may be required to recruit eligible patients.

Automatic Tube Compensation versus Pressure Support Ventilation and Extubation Outcome in Children: A Randomized Controlled Study

PubMed Central

El-beleidy, Ahmed Saad El-din; Khattab, Asser Abd EL-Hamied; El-Sherbini, Seham Awad; Al-gebaly, Hebatalla Fadel

2013-01-01

Background. Automatic tube compensation (ATC) has been developed to overcome the imposed work of breathing due to artificial airways during spontaneous breathing trials (SBTs). Objectives. This study aimed to assess extubation outcome after an SBT (spontaneous breathing trial) with ATC compared with pressure support ventilation (PSV) and to determine the risk factors for extubation failure. Methods. Patients ready for extubation were randomly assigned to two-hour spontaneous breathing trial with either ATC or pressure support ventilation. Results. In the ATC group (n = 17), 11 (65%) patients passed the SBT with subsequent extubation failure (9%). While in PSV group (n = 19), 10 (53%) patients passed the SBT with subsequent extubation failure (10%). This represented a positive predictive value for ATC of 91% and PSV of 90% (P = 0.52). Five (83%) of the patients who failed the SBT in ATC group were reintubated. This represented a higher negative predictive value for ATC of 83% than for PSV which was 56%. None of the assessed risk factors were independently associated with extubation failure including failed trial. Conclusion. ATC was equivalent to PSV in predicting patients with successful extubation. A trial failure in ATC group is associated with but does not definitely predict extubation failure. PMID:23533800

NHLBI's program for VAD therapy for moderately advanced heart failure: the REVIVE-IT pilot trial.

PubMed

Baldwin, J Timothy; Mann, Douglas L

2010-11-01

Ventricular assist devices (VADs) are used to bridge heart failure patients to transplantation, to allow their own hearts to recover, or as permanent ("destination") therapy. To date, the use of VADs has been limited to late-stage heart failure patients because of the associated device risks. In 2008, a National Heart, Lung, and Blood Institute (NHLBI) working group met to evaluate the treatment of heart failure using VADs and to advise the institute on how therapy for heart failure may be best advanced by clinical trials involving the devices. Recognizing the improvements in VAD technology and in patient care and selection over the past decade, the working group recommended that a trial be performed to assess the use of chronic VAD therapy in patients who are less ill than those currently eligible for destination therapy. The hypothesis proposed for the trial is that VAD therapy may improve both survival and quality of life in moderately advanced heart failure patients who are neither inotrope-dependent nor exercise-intolerant and have not yet developed serious consequences such as malnourishment, end-organ damage, and immobility. Based on the group's recommendations, NHLBI issued an RFP in 2009 for the REVIVE-IT Pilot Trail, which will serve to test the hypothesis and inform the pivotal trial. Published by Elsevier Inc.

NHLBI’s Program for VAD Therapy for Moderately Advanced Heart Failure: The REVIVE-IT Pilot Trial

PubMed Central

Baldwin, J. Timothy; Mann, Douglas L.

2010-01-01

Background VADs are used to bridge heart failure patients to transplantation, to allow their own hearts to recover, or as permanent (“destination”) therapy. To date, the use of VADs has been limited to late-stage heart failure patients because of the associated device risks. In 2008, an NHLBI working group met to evaluate the treatment of heart failure using VADs and to advise the institute on how therapy for heart failure may be best advanced by clinical trials involving the devices. Discussion and Recommendations Recognizing the improvements in VAD technology and in patient care and selection over the past decade, the working group recommended that a trial be performed to assess the use of chronic VAD therapy in patients who are less ill than those currently eligible for destination therapy. The hypothesis proposed for the trial is that VAD therapy may improve both survival and quality of life in moderately advanced heart failure patients who are neither inotrope-dependent nor exercise-intolerant and have not yet developed serious consequences such as malnourishment, end-organ damage, and immobility. Based on the group’s recommendations, NHLBI issued an RFP in 2009 for the REVIVE-IT Pilot Trail which will serve to test the hypothesis and inform the pivotal trial. PMID:21055648

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies.

PubMed

Li, Ling; Li, Sheyu; Deng, Ke; Liu, Jiali; Vandvik, Per Olav; Zhao, Pujing; Zhang, Longhao; Shen, Jiantong; Bala, Malgorzata M; Sohani, Zahra N; Wong, Evelyn; Busse, Jason W; Ebrahim, Shanil; Malaga, German; Rios, Lorena P; Wang, Yingqiang; Chen, Qunfei; Guyatt, Gordon H; Sun, Xin

2016-02-17

To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes. Systematic review and meta-analysis of randomised and observational studies. Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts. Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure. Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach. Eligible studies included 43 trials (n=68,775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1,777,358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15,701 v 33/12,591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18,554 v 552/18,474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use. The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use. 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.

Comprehensive approach for hypertension control in low-income populations: rationale and study design for the hypertension control program in Argentina.

PubMed

Mills, Katherine T; Rubinstein, Adolfo; Irazola, Vilma; Chen, Jing; Beratarrechea, Andrea; Poggio, Rosana; Dolan, Jacquelyn; Augustovski, Federico; Shi, Lizheng; Krousel-Wood, Marie; Bazzano, Lydia A; He, Jiang

2014-08-01

Although the efficacy and effectiveness of lifestyle modifications and antihypertensive pharmaceutical treatment for the prevention and control of hypertension and concomitant cardiovascular disease have been demonstrated in randomized controlled trials, this scientific knowledge has not been fully applied in the general population, especially in low-income communities. This article summarizes interventions to improve hypertension management and describes the rationale and study design for a cluster randomized trial testing whether a comprehensive intervention program within a national public primary care system will improve hypertension control among uninsured hypertensive men and women and their families. We will recruit 1,890 adults from 18 clinics within a public primary care network in Argentina. Clinic patients with uncontrolled hypertension, their spouses and hypertensive family members will be enrolled. The comprehensive intervention program targets the primary care system through health care provider education, a home-based intervention among patients and their families (home delivery of antihypertensive medication, self-monitoring of blood pressure [BP], health education for medication adherence and lifestyle modification) conducted by community health workers and a mobile health intervention. The primary outcome is net change in systolic BP from baseline to month 18 between intervention and control groups among hypertensive study participants. The secondary outcomes are net change in diastolic BP, BP control and cost-effectiveness of the intervention. This study will generate urgently needed data on effective, practical and sustainable intervention programs aimed at controlling hypertension and concomitant cardiovascular disease in underserved populations in low- and middle-income countries.

Comprehensive Approach for Hypertension Control in Low-income Populations: Rationale and Study Design for the Hypertension Control Program in Argentina (HCPIA)

PubMed Central

Mills, Katherine T.; Rubinstein, Adolfo; Irazola, Vilma; Chen, Jing; Beratarrechea, Andrea; Poggio, Rosana; Dolan, Jacquelyn; Augustovski, Federico; Shi, Lizheng; Krousel-Wood, Marie; Bazzano, Lydia A.; He, Jiang

2014-01-01

Although the efficacy and effectiveness of lifestyle modifications and antihypertensive pharmaceutical treatment for the prevention and control of hypertension and concomitant cardiovascular disease have been demonstrated in randomized controlled trials, this scientific knowledge has not been fully applied in the general population, especially in low-income communities. This paper summarizes interventions to improve hypertension management and describes the rationale and study design for a cluster randomized trial testing whether a comprehensive intervention program within a national public primary care system will improve hypertension control among uninsured hypertensive men and women and their families. We will recruit 1,890 adults from 18 clinics within a public primary care network in Argentina. Clinic patients with uncontrolled hypertension, their spouses and hypertensive family members will be enrolled. The comprehensive intervention program targets the primary care system through health care provider education, a home-based intervention among patients and their families (home delivery of antihypertensive medication, self-monitoring of blood pressure, health education for medication adherence and lifestyle modification) conducted by community health workers, and a mobile health intervention. The primary outcome is net change in systolic blood pressure from baseline to month 18 between intervention and control groups among hypertensive study participants. The secondary outcomes are net change in diastolic blood pressure, blood pressure control, and cost-effectiveness of the intervention. This study will generate urgently needed data on effective, practical, and sustainable intervention programs aimed at controlling hypertension and concomitant cardiovascular disease in underserved populations in low- and middle-income countries. PMID:24978148

Machine learning of big data in gaining insight into successful treatment of hypertension.

PubMed

Koren, Gideon; Nordon, Galia; Radinsky, Kira; Shalev, Varda

2018-06-01

Despite effective medications, rates of uncontrolled hypertension remain high. Treatment protocols are largely based on randomized trials and meta-analyses of these studies. The objective of this study was to test the utility of machine learning of big data in gaining insight into the treatment of hypertension. We applied machine learning techniques such as decision trees and neural networks, to identify determinants that contribute to the success of hypertension drug treatment on a large set of patients. We also identified concomitant drugs not considered to have antihypertensive activity, which may contribute to lowering blood pressure (BP) control. Higher initial BP predicts lower success rates. Among the medication options and their combinations, treatment with beta blockers appears to be more commonly effective, which is not reflected in contemporary guidelines. Among numerous concomitant drugs taken by hypertensive patients, proton pump inhibitors (PPIs), and HMG CO-A reductase inhibitors (statins) significantly improved the success rate of hypertension. In conclusions, machine learning of big data is a novel method to identify effective antihypertensive therapy and for repurposing medications already on the market for new indications. Our results related to beta blockers, stemming from machine learning of a large and diverse set of big data, in contrast to the much narrower criteria for randomized clinic trials (RCTs), should be corroborated and affirmed by other methods, as they hold potential promise for an old class of drugs which may be presently underutilized. These previously unrecognized effects of PPIs and statins have been very recently identified as effective in lowering BP in preliminary clinical observations, lending credibility to our big data results.

Cardiovascular events in subgroups of patients during primary treatment of hypertension with candesartan or losartan.

PubMed

Russell, David; Stålhammar, Jan; Bodegard, Johan; Hasvold, Pål; Thuresson, Marcus; Kjeldsen, Sverre E

2011-03-01

Merging data from existing electronic patient records, and electronic hospital discharge and cause of death registers, is a fast and relatively inexpensive method for comparing different treatments with regard to clinical outcome. This study compared the effects of antihypertensive treatment with candesartan or losartan on cardiovascular disease (CVD) using Swedish registers. Patients without previous CVD who were prescribed candesartan (n=7329) or losartan (n=6771) for hypertension during 1999-2007 at 72 Swedish primary care centers were followed for up to 9 years. Both medications were given according to current recommendations, and there was no difference observed in achieved blood pressures. The authors have previously shown that candesartan lowered the risk of all CVD (primary composite end point) more so than losartan (adjusted hazard ratio, 0.86; 95% confidence interval, 0.77-0.96). Candesartan also had a significantly better effect with regards to reducing the development of heart failure, cardiac arrhythmias, and peripheral arterial disease. In the present analysis, the authors found that candesartan, compared with losartan, reduced the risk of all CVD, irrespective of sex, age, previous antihypertensive treatment, baseline blood pressure, and presence of diabetes. These clinical findings may reflect differences between candesartan and losartan in their binding characteristics to the angiotensin type 1 receptor. © 2010 Wiley Periodicals, Inc.

Evaluation and management of the patient with difficult-to-control or resistant hypertension.

PubMed

Viera, Anthony J; Hinderliter, Alan L

2009-05-15

High blood pressure is often difficult to control. Resistant hypertension is blood pressure above goal despite adherence to a combination of at least three antihypertensive medications of different classes, optimally dosed and usually including a diuretic. The approach to blood pressure that is apparently difficult to control begins with an assessment of the patient's adherence to the management plan, including lifestyle modifications and medications. White-coat hypertension may need to be ruled out. Suboptimal therapy is the most common reason for failure to reach the blood pressure goal. Once-daily fixed-dose combination pills may improve control through the synergism of antihypertensive agents from different classes and improved adherence. Truly drug-resistant hypertension is commonly caused by chronic kidney disease, obstructive sleep apnea, or hyperaldosteronism, all of which can lead to fluid retention. Higher doses of diuretics (or a change to a loop diuretic) are usually needed. Other strategies include adding an alpha blocker, alpha-beta blocker, clonidine, or an aldosterone antagonist (e.g., spironolactone). Particularly in patients with diabetes or renal disease, combining a long-acting nondihydropyridine with a dihydropyridine calcium channel . blocker can also be considered. Obesity, heavy alcohol intake, high levels of dietary sodium, and interfering substances (especially nonsteroidal anti-inflammatory drugs) contribute to hypertension that is resistant or difficult to control.

Antihypertensive potential of bioactive hydrolysate from edible bird's nest

NASA Astrophysics Data System (ADS)

Ramachandran, Ravisangkar; Babji, Abdul Salam; Sani, Norrakiah Abdullah

2018-04-01

The aim of this study is to determine and compare the proximate composition, the degree of hydrolysis (DH) and the antihypertensive activity of edible bird's nest (EBN) hydrolysates of two different drying methods. Four types of enzymes (alcalase, bromelain, pancreatin and papain) were used in this study and with different hydrolysis time (30, 60, 90, 120, 180 and 240 min). The highest DH for alcalase (79.48 - 84.09%), pancreatine (77.10 - 80.45%) and papain (82.33%) for EBN hydrolysates was produced with alcalase treatment at 60 - 90 min, pancreatine treatment at 30 - 90 min and papain treatment at 90 min. Bromelain generated hydrolysates showed low DH. EBN hydrolysed using alcalase, pancreatin and papain have significantly higher protein content compared to raw EBN and the moisture content of all hydrolysates treatments was significantly lower compared to raw EBN. For antihypertensive assay, freeze dried EBN hydrolysates have higher antihypertensive activity compared to spray dried hydrolysates. The highest antihypertensive activity for freeze dried samples was produced by alcalase, bromelain and pancreatin and in the range of 80.22 - 86.97%. Meanwhile, papain proved to be less effective in producing hydrolysate with antihypertensive ability. In conclusion, EBN hydrolysate prepared by alcalase, bromelain and pancreatin could be classified as a functional food as it showed significant antihypertensive activity.

Antihypertensive agents and risk of Parkinson's disease, essential tremor and dementia: a population-based prospective study (NEDICES).

PubMed

Louis, Elan D; Benito-León, Julián; Bermejo-Pareja, Félix

2009-01-01

Recent interest in antihypertensive agents, especially calcium channel blockers, has been sparked by the notion that these medications may be neuroprotective. A modest literature, with mixed results, has examined whether these medications might lower the odds or risk of Parkinson's disease (PD) or dementia. There are no data for essential tremor (ET). To examine the association between antihypertensive use (defined broadly and by individual subclasses) and ET, PD and dementia. For each disorder, we used cross-sectional data (association with prevalent disease) and prospective data (association with incident disease). Prospective population-based study in Spain enrolling 5,278 participants at baseline. Use of antihypertensive medications (aside from beta-blockers) was similar in prevalent ET cases and controls. Baseline use of antihypertensive agents was not associated with reduced risk of incident ET. Antihypertensive medication use was not associated with prevalent or incident PD. Calcium channel blocker use was marginally reduced in prevalent dementia cases (OR(adjusted) = 0.63, p = 0.06) but was not associated with reduced risk of incident dementia (RR(adjusted) = 1.02, p = 0.95). We did not find evidence of a protective effect of antihypertensive medications in these three neurodegenerative disorders. Copyright 2009 S. Karger AG, Basel.

LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial.

PubMed

Masmiquel, L; Leiter, L A; Vidal, J; Bain, S; Petrie, J; Franek, E; Raz, I; Comlekci, A; Jacob, S; van Gaal, L; Baeres, F M M; Marso, S P; Eriksson, M

2016-02-10

Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). Mean BMI was 32.5 ± 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints.

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

PubMed

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

2017-01-01

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

Progression of kidney disease in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin versus usual care: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

PubMed

Rahman, Mahboob; Baimbridge, Charles; Davis, Barry R; Barzilay, Joshua; Basile, Jan N; Henriquez, Mario A; Huml, Anne; Kopyt, Nelson; Louis, Gail T; Pressel, Sara L; Rosendorff, Clive; Sastrasinh, Sithiporn; Stanford, Carol

2008-09-01

Dyslipidemia is common in patients with chronic kidney disease. The role of statin therapy in the progression of kidney disease is unclear. Prospective randomized clinical trial, post hoc analyses. 10,060 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) stratified by baseline estimated glomerular filtration rate (eGFR): less than 60, 60 to 89, and 90 or greater mL/min/1.73 m(2). Mean follow-up was 4.8 years. Randomized; pravastatin, 40 mg/d, or usual care. Total, high-density lipoprotein, and low-density lipoprotein cholesterol; end-stage renal disease (ESRD), eGFR. Through year 6, total cholesterol levels decreased in the pravastatin (-20.7%) and usual-care groups (-11.2%). No significant differences were seen between groups for rates of ESRD (1.36 v 1.45/100 patient-years; P = 0.9), composite end points of ESRD and 50% or 25% decrease in eGFR, or rate of change in eGFR. Findings were consistent across eGFR strata. In patients with eGFR of 90 mL/min/1.73 m(2) or greater, the pravastatin arm tended to have a higher eGFR. Proteinuria data unavailable, post hoc analyses, unconfirmed validity of the Modification of Diet in Renal Disease Study equation in normal eGFR range, statin drop-in rate in usual-care group with small cholesterol differential between groups. In hypertensive patients with moderate dyslipidemia and decreased eGFR, pravastatin was not superior to usual care in preventing clinical renal outcomes. This was consistent across the strata of baseline eGFR. However, benefit from statin therapy may depend on the degree of the cholesterol level decrease achieved.

Progression of Kidney Disease in Moderately Hypercholesterolemic, Hypertensive Patients Randomized to Pravastatin Versus Usual Care: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

PubMed Central

Rahman, Mahboob; Baimbridge, Charles; Davis, Barry R.; Barzilay, Joshua; Basile, Jan N.; Henriquez, Mario A.; Huml, Anne; Kopyt, Nelson; Louis, Gail T.; Pressel, Sara L.; Rosendorff, Clive; Sastrasinh, Sithiporn; Stanford, Carol

2009-01-01

Background Dyslipidemia is common in patients with chronic kidney disease. The role of statin therapy on the progression of kidney disease is unclear. Study Design Prospective randomized clinical trial, post hoc analyses. Setting and participants 10,060 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (lipid-lowering component) stratified by baseline eGFR: <60, 60–89, ≥90 mL/min/1.73 m2. Mean follow-up was 4.8 years. Intervention Randomized, pravastatin 40 mg/day or usual care. Outcomes and measurements Total cholesterol, HDL- and LDL-cholesterol; end stage renal disease (ESRD), estimated glomerular filtration rate (eGFR). Results Through year six, total cholesterol declined in the pravastatin (−20.7%) and usual care groups (−11.2%). No significant differences were seen between the groups for rates of ESRD (1.36 vs 1.45/100 patient years, P=0.9), composite endpoints of ESRD and 50% or 25% decline in eGFR, or rate of change of eGFR. Findings were consistent across eGFR strata. In patients with eGFR≥90 mL/min/1.73 m2, the pravastatin arm tended to have a higher eGFR. Limitations Proteinuria data unavailable, post hoc analyses, unconfirmed validity of the Modification of Diet in Renal Disease Study equation in normal eGFR range, statin drop-in rate in usual care group with small cholesterol differential between groups. Conclusions In hypertensive patients with moderate dyslipidemia and reduced eGFR, pravastatin was not superior to usual care in preventing clinical renal outcomes. This was consistent across the strata of baseline eGFR. However, benefit from statin therapy may depend on degree of cholesterol reduction achieved. PMID:18676075

Predicting subsequent task performance from goal motivation and goal failure.

PubMed

Healy, Laura C; Ntoumanis, Nikos; Stewart, Brandon D; Duda, Joan L

2015-01-01

Recent research has demonstrated that the cognitive processes associated with goal pursuit can continue to interfere with unrelated tasks when a goal is unfulfilled. Drawing from the self-regulation and goal-striving literatures, the present study explored the impact of goal failure on subsequent cognitive and physical task performance. Furthermore, we examined if the autonomous or controlled motivation underpinning goal striving moderates the responses to goal failure. Athletes (75 male, 59 female, Mage = 19.90 years, SDage = 3.50) completed a cycling trial with the goal of covering a given distance in 8 min. Prior to the trial, their motivation was primed using a video. During the trial they were provided with manipulated performance feedback, thus creating conditions of goal success or failure. No differences emerged in the responses to goal failure between the primed motivation or performance feedback conditions. We make recommendations for future research into how individuals can deal with failure in goal striving.

Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation.

PubMed

Duffy, Jmn; Hirsch, M; Pealing, L; Showell, M; Khan, K S; Ziebland, S; McManus, R J

2018-06-01

Randomised trials and their syntheses in meta-analyses offer a unique opportunity to assess the frequency and severity of adverse reactions. To assess safety reporting in pre-eclampsia trials. Systematic search using bibliographic databases, including Cochrane Central Register of Controlled Trials, Embase, and MEDLINE, from inception to August 2017. Randomised trials evaluating anticonvulsant or antihypertensive medication for pre-eclampsia. Descriptive statistics appraising the adequacy of adverse reaction and toxicity reporting. We included 60 randomised trials. Six trials (10%) were registered with the International Clinical Trials Registry Platform, two registry records referred to adverse reactions, stating 'safety and toleration' and 'possible side effects' would be collected. Twenty-six trials (43%) stated the frequency of withdrawals within each study arm, and five trials (8%) adequately reported these withdrawals. Adverse reactions were inconsistently reported across eligible trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no mild adverse reactions. The methods of definition or measurement of adverse reactions were infrequently reported within published trial reports. Pre-eclampsia trials regularly omit critical information related to safety. Despite the paucity of reporting, randomised trials collect an enormous amount of safety data. Developing and implementing a minimum data set could help to improve safety reporting, permitting a more balanced assessment of interventions by considering the trade-off between the benefits and harms. National Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal Society of Medicine, UK. Developing @coreoutcomes could help to improve safety reporting in #preeclampsia trials. @NIHR_DC. © 2017 Royal College of Obstetricians and Gynaecologists.

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

PubMed

Townsend, Raymond R; Mahfoud, Felix; Kandzari, David E; Kario, Kazuomi; Pocock, Stuart; Weber, Michael A; Ewen, Sebastian; Tsioufis, Konstantinos; Tousoulis, Dimitrios; Sharp, Andrew S P; Watkinson, Anthony F; Schmieder, Roland E; Schmid, Axel; Choi, James W; East, Cara; Walton, Anthony; Hopper, Ingrid; Cohen, Debbie L; Wilensky, Robert; Lee, David P; Ma, Adrian; Devireddy, Chandan M; Lea, Janice P; Lurz, Philipp C; Fengler, Karl; Davies, Justin; Chapman, Neil; Cohen, Sidney A; DeBruin, Vanessa; Fahy, Martin; Jones, Denise E; Rothman, Martin; Böhm, Michael

2017-11-11

Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. Medtronic. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Clonidine versus captopril for treatment of postpartum very high blood pressure: study protocol for a randomized controlled trial (CLONCAP)

PubMed Central

2013-01-01

Background The behavior of arterial blood pressure in postpartum of women with hypertension and pregnancy and the best treatment for very high blood pressure in this period still need evidence. The Cochrane systematic review assessing prevention and treatment of postpartum hypertension found only two trials (120 patients) comparing hydralazine with nifedipine and labetalol for the treatment of severe hypertension and did not find enough evidence to know how best to treat women with hypertension after birth. Although studies have demonstrated the effectiveness of treatment with captopril, side effects were reported. Because of these findings, new classes of antihypertensive drugs began to be administered as an alternative therapy. Data on the role of clonidine in this particular group of patients, its effects in the short and long term are still scarce in the literature. Objectives To determine the effectiveness of clonidine, compared to captopril, for the treatment of postpartum very high blood pressure in women with hypertension in pregnancy. Methods/design The study is a triple blind randomized controlled trial including postpartum women with diagnosis of hypertension in pregnancy presenting very high blood pressure, and exclusion criteria will be presence of heart disease, smoking, use of illicit drugs, any contraindication to the use of captopril or clonidine and inability to receive oral medications. Eligible patients will be invited to participate and those who agree will be included in the study and receive captopril or clonidine according to a random list of numbers. The subjects will receive the study medication every 20 minutes until blood pressure is over 170 mmHg of systolic blood pressure and 110 mmHg diastolic blood pressure. A maximum of six pills a day for very high blood pressure will be administered. In case of persistent high blood pressure levels, other antihypertensive agents will be used. During the study the women will be subject to strict control of blood pressure and urine output. This proposal has already obtained approval of the local Institutional Review Board of the coordinating center (IMIP, Recife, Brazil) and of the National Council for Ethics in Research (CONEP) of the Brazilian Ministry of Health. Trial registration Clinical Trials Register under the number NCT01761916. PMID:23899372

Rationale and design of the Aquapheresis Versus Intravenous Diuretics and Hospitalization for Heart Failure (AVOID-HF) trial.

PubMed

Costanzo, Maria Rosa; Negoianu, Daniel; Fonarow, Gregg C; Jaski, Brian E; Bart, Bradley A; Heywood, J Thomas; Nabut, Jose L; Schollmeyer, Michael P

2015-09-01

In patients hospitalized with acutely decompensated heart failure, unresolved signs and symptoms of fluid overload have been consistently associated with poor outcomes. Regardless of dosing and type of administration, intravenous loop diuretics have not reduced heart failure events or mortality in patients with acutely decompensated heart failure. The results of trials comparing intravenous loop diuretics to mechanical fluid removal by isolated venovenous ultrafiltration have yielded conflicting results. Studies evaluating early decongestive strategies have shown that ultrafiltration removed more fluid and was associated with fewer heart failure-related rehospitalization than intravenous loop diuretics. In contrast, when used in the setting of worsening renal function, ultrafiltration was associated with poorer renal outcomes and no reduction in heart failure events. The AVOID-HF trial seeks to determine if an early strategy of ultrafiltration in patients with acutely decompensated heart failure is associated with fewer heart failure events at 90 days compared with a strategy based on intravenous loop diuretics. Study subjects from 40 highly experienced institutions are randomized to either early ultrafiltration or intravenous loop diuretics. In both treatment arms, fluid removal therapies are adjusted according to the patients' hemodynamic condition and renal function. The study was unilaterally terminated by the sponsor in the absence of futility and safety concerns after the enrollment of 221 subjects, or 27% of the originally planned sample size of 810 patients. The AVOID-HF trial's principal aim is to compare the safety and efficacy of ultrafiltration vs that of intravenous loop diuretics in patients hospitalized with acutely decompensated heart failure. Because stepped treatment approaches are applied in both ultrafiltration and intravenous loop diuretics groups and the primary end point is time to first heart failure event within 90 days, it is hoped that the AVOID-HF trial, despite its untimely termination by the sponsor, will provide further insight on how to optimally decongest patients with fluid-overloaded heart failure. Copyright © 2015. Published by Elsevier Inc.

Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent, and difficult.

PubMed

Rosenblum, William I

2014-05-01

Before amyloid formation, peptides cleaved from the amyloid precursor protein (APP) exist as soluble oligomers. These are extremely neurotoxic. Their concentration is strongly correlated with synaptic impairment in animals and parallel cognitive decline in animals and humans. Clinical trials have largely been aimed at removing insoluble beta amyloid in senile plaques and have not reduced soluble load. Even treatment that should remove soluble oligomers has not consistently reduced the load. Failure to significantly improve cognition has frequently been attributed to failure of the amyloid hypothesis or to irreversible alteration in the brain. Instead, trial failures may be because of failure to significantly reduce load of toxic Aβ oligomers. Moreover, targeting only synthesis of Aβ peptides, only the oligomers themselves, or only the final insoluble amyloid may fail to significantly reduce soluble load because of the interrelationship between these 3 points in the amyloid cascade. Thus, treatments may fail unless trials target simultaneously all 3 points in the equation-"triple therapy". Cerebrospinal fluid analysis and other monitoring tools may in the future provide reliable measurement of soluble load. But currently, only analysis of autopsied brains can provide this data and thus enable proper evaluation and explanation of the outcome of clinical trials. These data are essential before attributing trial failures to the advanced nature of the disease or asserting that failures prove that the theory linking Alzheimer's disease to products of amyloid precursor protein is incorrect. Copyright © 2014 Elsevier Inc. All rights reserved.

Overview of clinical use and side effect profile of valsartan in Chinese hypertensive patients

PubMed Central

Huang, Qi-Fang; Li, Yan; Wang, Ji-Guang

2014-01-01

We reviewed the Chinese and English literature for the efficacy and safety data of valsartan monotherapy or combination therapy in Chinese hypertensive patients. According to the data of ten randomized controlled trials, valsartan monotherapy was as efficacious as another angiotensin receptor blocker or other classes of antihypertensive drugs, excepting the slightly inferior diastolic blood pressure-lowering effect in comparison with calcium channel blockers. According to the data of six randomized controlled trials, valsartan combination, with hydrochlorothiazide, amlodipine, or nifedipine gastrointestinal therapeutic system, was more efficacious than monotherapy of valsartan, amlodipine, or nifedipine gastrointestinal therapeutic system. According to these trials, valsartan had an acceptable tolerability, regardless of whether it was used as monotherapy or in combination therapy. Nonetheless, several rare side effects have been reported, indicating that it should still be used with caution. This is of particular importance given that there are millions of hypertensive patients, worldwide, currently exposed to the drug. PMID:24403822

Advances in gene therapy for heart failure.

PubMed

Fish, Kenneth M; Ishikawa, Kiyotake

2015-04-01

Chronic heart failure is expected to increase its social and economic burden as a consequence of improved survival in patients with acute cardiac events. Cardiac gene therapy holds significant promise in heart failure treatment for patients with currently very limited or no treatment options. The introduction of adeno-associated virus (AAV) gene vector changed the paradigm of cardiac gene therapy, and now it is the primary vector of choice for chronic heart failure gene therapy in clinical and preclinical studies. Recently, there has been significant progress towards clinical translation in this field spearheaded by AAV-1 mediated sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) gene therapy targeting chronic advanced heart failure patients. Meanwhile, several independent laboratories are reporting successful gene therapy approaches in clinically relevant large animal models of heart failure and some of these approaches are expected to enter clinical trials in the near future. This review will focus on gene therapy approaches targeting heart failure that is in clinical trials and those close to its initial clinical trial application.

Patient Selection in Heart Failure With Preserved Ejection Fraction Clinical Trials

PubMed Central

Kelly, Jacob P.; Mentz, Robert J.; Mebazaa, Alexandre; Voors, Adriaan A.; Butler, Javed; Roessig, Lothar; Fiuzat, Mona; Zannad, Faiez; Pitt, Bertram; O’Connor, Christopher M.; Lam, Carolyn S.P.

2015-01-01

Recent clinical trials in patients with heart failure with preserved ejection fraction (HFpEF) have provided important insights into participant selection strategies. Historically, HFpEF trials have included patients with relatively preserved left ventricular ejection fraction ranging from 40% to 55% and a clinical history of heart failure. Contemporary HFpEF trials have also incorporated inclusion criteria such as hospitalization for HFpEF, altered functional capacity, cardiac structural and functional abnormalities, and abnormalities in neurohormonal status (e.g., elevated natriuretic peptide levels). Careful analyses of the impact of these patient selection criteria on outcomes in prior trials provide valuable lessons for future trial design. We review recent and ongoing HFpEF clinical trials from a patient selection perspective and appraise trial patient selection methodologies in relation to outcomes. This review reflects discussions between clinicians, scientists, trialists, regulators, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum in Paris, France on December 6, 2013. PMID:25908073

Antihypertensive efficacy of the losartan/hydrochlorothiazide combination and its effect on plasma B-type natriuretic peptide in hypertensive patients uncontrolled by angiotensin II type 1 receptor antagonist-based therapy: a multicentre prospective observational study.

PubMed

Meno, Hiroshi; Inou, Tetsuji; Tanaka, Michiko; Tsuchiya, Yoshihiro; Shiga, Yuhei; Kobayashi, Kenji; Nakamura, Yuichiro; Ota, Takeaki; Kubara, Ichiro

2012-03-01

Although strict blood pressure (BP) control is effective in the prevention of cardiovascular events, it is often insufficient in many hypertensive patients. B-type natriuretic peptide (BNP) has been shown to be associated with cardiovascular events. We investigated the effects of the losartan/hydrochlorothiazide combination on BP and plasma BNP in hypertensive patients uncontrolled by an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB])-based therapy. In a multicentre prospective observational study, we enrolled 185 patients aged 36-79 years (mean age 63.8 years) with essential hypertension but without symptoms of heart failure who received an ARB-based therapy for ≥3 months but failed to achieve a target BP recommended by the Japanese Society of Hypertension (JSH). ARBs were switched to losartan (LOS) 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg. The antihypertensive efficacy, safety, and effects of this combination on blood biochemical parameters and plasma BNP were evaluated for 12 months. Mean ± SD systolic and diastolic BP decreased from 152 ± 13/87 ± 10 mmHg to 128 ± 14/74 ± 10 mmHg, respectively, after 12 months (p < 0.001). Mean ± SD plasma BNP levels decreased significantly from 46.0 ± 83.0 pg/mL to 40.8 ± 68.0 pg/mL (p < 0.05). The percentage of patients who achieved the JSH 2004 target BP was 51% after 12 months; the percentage was 63% in elderly patients aged ≥65 years without complications, and 43% in patients with concomitant diabetes mellitus or chronic kidney disease. No association was found between a decrease in plasma BNP levels and BP, age, body mass index or estimated glomerular filtration rate. There was a significant increase in serum uric acid and a decrease in serum potassium, but both were within the range of normal values. Adverse events were observed in 8.6% of the patients. Antihypertensive treatment using two types of drugs (LOS/HCTZ) with different mechanisms yielded potent antihypertensive efficacy with safety and decreased plasma BNP levels.

Hypertension: adherence to treatment in rural Bangladesh – findings from a population-based study

PubMed Central

Khanam, Masuma Akter; Lindeboom, Wietze; Koehlmoos, Tracey Lynn Perez; Alam, Dewan Shamsul; Niessen, Louis; Milton, Abul Hasnat

2014-01-01

Background Poor adherence has been identified as the main cause of failure to control hypertension. Poor adherence to antihypertensive treatment is a significant cardiovascular risk factor, which often remains unrecognized. There are no previous studies that examined adherence with antihypertensive medication or the characteristics of the non-adherent patients in Bangladesh. Objective This paper aims to describe hypertension and factors affecting adherence to treatment among hypertensive persons in rural Bangladesh. Design The study population included 29,960 men and women aged 25 years and older from three rural demographic surveillance sites of the International Center for Diarrheal Disease Research, Bangladesh (icddr,b): Matlab, Abhoynagar, and Mirsarai. Data was collected by a cross-sectional design on diagnostic provider, initial, and current treatment. Discontinuation of medication at the time of interview was defined as non-adherence to treatment. Results The prevalence of hypertension was 13.67%. Qualified providers diagnosed only 53.5% of the hypertension (MBBS doctors 46.1 and specialized doctors 7.4%). Among the unqualified providers, village doctors diagnosed 40.7%, and others (nurse, health worker, paramedic, homeopath, spiritual healer, and pharmacy man) each diagnosed less than 5%. Of those who started treatment upon being diagnosed with hypertension, 26% discontinued the use of medication. Age, sex, education, wealth, and type of provider were independently associated with non-adherence to medication. More men discontinued the treatment than women (odds ratio [OR] 1.74, confidence interval [CI] 1.48–2.04). Non-adherence was greater when hypertension was diagnosed by unqualified providers (OR 1.52, CI 1.31–1.77). Hypertensive patients of older age, least poor quintile, and higher education were less likely to be non-adherent. Patients with cardiovascular comorbidity were also less likely to be non-adherent to antihypertensive medication (OR 0.79, CI 0.64–0.97). Conclusions Although village doctors diagnose 40% of hypertension, their treatments are associated with a higher rate of non-adherence to medication. The hypertension care practices of the village doctors should be explored by additional research. More emphasis should be placed on men, young people, and people with low education. Health programs focused on education regarding the importance of taking continuous antihypertensive medication is now of utmost importance. PMID:25361723

Recruitment failure and futility were the most common reasons for discontinuation of clinical drug trials. Results of a nationwide inception cohort study in the Netherlands.

PubMed

van den Bogert, Cornelis A; Souverein, Patrick C; Brekelmans, Cecile T M; Janssen, Susan W J; Koëter, Gerard H; Leufkens, Hubert G M; Bouter, Lex M

2017-08-01

The objective of the study was to identify the reasons for discontinuation of clinical drug trials and to evaluate whether efficacy-related discontinuations were adequately planned in the trial protocol. All clinical drug trials in the Netherlands, reviewed by institutional review boards in 2007, were followed until December 2015. Data were obtained through the database of the Dutch competent authority (Central Committee on Research Involving Human Subjects [CCMO]) and a questionnaire to the principal investigators. Reasons for trial discontinuation were the primary outcome of the study. Three reasons for discontinuation were analyzed separately: all cause, recruitment failure, and efficacy related (when an interim analysis had demonstrated futility or superiority). Among the efficacy-related discontinuations, we examined whether the data monitoring committee, the stopping rule, and the moment of the interim analysis in the trial progress were specified in the trial protocol. Of the 574 trials, 102 (17.8%) were discontinued. The most common reasons were recruitment failure (33 of 574; 5.7%) and solely efficacy related (30 of 574; 5.2%). Of the efficacy-related discontinuations, 10 of 30 (33.3%) of the trial protocols reported all three aspects in the trial protocol, and 20 of 30 (66.7%) reported at least one aspect in the trial protocol. One out of five clinical drug trials is discontinued before the planned trial end, with recruitment failure and futility as the most common reasons. The target sample size of trials should be feasible, and interim analyses should be adequately described in trial protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study.

PubMed

Avanzini, F; Palumbo, G; Alli, C; Roncaglioni, M C; Ronchi, E; Cristofari, M; Capra, A; Rossi, S; Nosotti, L; Costantini, C; Pietrofeso, R

2000-06-01

Nonsteroidal antiinflammatory drugs may affect blood pressure (BP) control in hypertensive patients receiving drug treatment, but data on the effects of low-dose aspirin are scanty. This study assessed the effects of chronic treatment with low doses of aspirin (100 mg/day) on clinic and ambulatory systolic (SBP) and diastolic (DBP) BP in hypertensives on chronic, stable antihypertensive therapy. The study was conducted in the framework of the Primary Prevention Project (PPP), a randomized, controlled factorial trial on the preventive effect of aspirin or vitamin E in people with one or more cardiovascular risk factors. Fifteen Italian hypertension units studied 142 hypertensive patients (76 men, 66 women; mean age 59 +/- 5.9 years) treated with different antihypertensive drugs: 71 patients were randomized to aspirin and 71 served as controls. All patients underwent a clinic BP evaluation with an automatic sphygmomanometer and a 24-h ambulatory BP monitoring, at baseline and after 3 months of aspirin treatment. At the end of the study the changes in clinic SBP and DBP were not statistically different in treated and untreated subjects. Ambulatory SBP and DBP after 3 months of aspirin treatment were similar to baseline: deltaSBP -0.5 mmHg (95% confidence intervals [CI] from -1.9 to +2.9 mm Hg) and deltaDBP -1.1 mm Hg (95% CI from -2.5 to +0.3 mm Hg). The pattern was similar in the control group. No interaction was found between aspirin and the most used antihypertensive drug classes (angiotensin converting enzyme inhibitors and calcium antagonists). Despite the relatively small sample size our results seem to exclude any significant influence of low-dose aspirin on BP control in hypertensives under treatment.

The Hypertension Optimal Treatment (HOT) Study--patient characteristics: randomization, risk profiles, and early blood pressure results.

PubMed

Hansson, L; Zanchetti, A

1994-09-01

The Hypertension Optimal Treatment (HOT) Study is a prospective, randomized, multicenter trial being conducted in 26 countries. Its main aim is to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and cardiovascular morbidity and mortality in hypertensive patients. In addition, the study will examine the effects on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) or placebo. In the HOT Study, basic antihypertensive treatment is initiated with the calcium antagonist felodipine at a dose of 5 mg daily. If target blood pressure is not reached, additional antihypertensive therapy with either an angiotensin converting enzyme (ACE) inhibitor or a beta-adrenoceptor blocking agent is given. Further dosage adjustments are made in accordance with a set protocol. As a fifth and final step, a diuretic may be added. Inclusion of patients was stopped on April 30, 1994. At that time 19,196 patients had been randomized. There were 9,055 (47%) women and 10,141 (53%) men with an average age of 61.5 +/- 7.5 (SD) years. At enrollment, 52% of patients were receiving antihypertensive treatment. These patients entered a wash-out period of at least 2 weeks before randomization. The average randomization blood pressure in untreated patients was 169 +/- 14/106 +/- 3 mmHg and in the treated patients 170 +/- 14/105 +/- 3 mmHg. On August 15, 1994, blood pressure data were available for 14,710 and 10,275 patients, who had completed 3 and 6 months treatment, respectively. The average reduction in diastolic blood pressure was 22 mmHg after 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary flavonoids added to pharmacological antihypertensive therapy are effective in improving blood pressure.

PubMed

de Jesús Romero-Prado, Marina María; Curiel-Beltrán, Jesús Aarón; Miramontes-Espino, María Viviana; Cardona-Muñoz, Ernesto Germán; Rios-Arellano, Angeles; Balam-Salazar, Lol-Be

2015-07-01

Epidemiological studies have suggested that the daily intake of flavonoids is associated with a decreased risk of developing cardiovascular disease. Our purpose was to evaluate the effect of the addition of dietary flavonoids (DF) to antihypertensive treatment (AHT), based on telmisartan (Tms) or captopril (Cpr), on blood pressure (BP), body mass index (BMI), waist/hip ratio, leptin, lipid profile and inflammation in hypertensive young patients. An open-label, randomized, controlled trial was performed among 79 patients aged 20-55 years with grade I or grade II systemic arterial hypertension. The subjects were assigned to one of four groups for AHT plus DF during 6 months: Cpr (n = 14), Cpr + DF (n = 19), Tms (n = 25) and Tms + DF (n = 21). DF consisted of dark chocolate, dehydrated red apple and green tea in an infusion to obtain a daily dose of 425.8 ± 13.9 mg epicatechin equivalents. The BP and anthropometric parameters were measured every 2 weeks. Lipid profile, leptin and hsCRP were determined by standard methods. The combination AHT-DF produced an additional and significant reduction in (i) SBP/DBP of -5/-4 mmHg, being -7/-5 for Cpr + DF and -4/-3 for Tms + DF; (ii) triglyceride levels (-30.6%) versus AHT alone (-9.6%); and (iii) leptin: Cpr + DF versus Tms + DF (p < 0.005). Finally, C-reactive protein plasma levels were reduced significantly in all groups independently of the applied treatment. We conclude that the addition of flavonoids to pharmacological antihypertensive therapy shows additional benefits on BP, lipid profile, leptin, obesity and inflammation. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Population impact of the 2017 ACC/AHA guidelines compared with the 2013 ESH/ESC guidelines for hypertension management.

PubMed

Vaucher, Julien; Marques-Vidal, Pedro; Waeber, Gérard; Vollenweider, Peter

2018-01-01

Background The 2017 ACC/AHA guidelines on hypertension management recommend the introduction of antihypertensive treatment for patients with new stage 1 hypertension thresholds (130-139/80-89 mm Hg) and with a cardiovascular disease or related condition. We compared the Swiss population and economic impact of antihypertensive treatment of the 2017 ACC/AHA guidelines with the 2013 European guidelines. Methods Analyses were based on 4438 participants (aged 45-85 years; 2448 women) of the CoLaus|PsyCoLaus study recruited between 2014-2017. Participants eligible for antihypertensive treatment according to the 2017 ACC/AHA and 2013 European guidelines were sex and age standardised using the Swiss population for 2016. In addition, we estimated the population-wide annual costs of antihypertensive treatment. Results Individuals eligible for antihypertensive treatment were 40.3% (95% confidence interval 38.5-42.1) and 31.3% (29.7-32.9) according to the 2017 ACC/AHA and 2013 European guidelines, respectively. That difference would translate into approximately 250,000 additional individuals eligible for antihypertensive treatment, corresponding to an additional annual cost of 72.5 million CHF (63.0 million EUR). Conclusion The 2017 ACC/AHA guidelines on the management of hypertension substantially increase the number of individuals eligible for antihypertensive treatment compared to the 2013 European guidelines. While implementation of the 2017 ACC/AHA guidelines is expected to lead to cost reduction by preventing cardiovascular diseases, that reduction might be mitigated by the costs incurred by antihypertensive treatments in a larger proportion of the population.

How Ghanaian, African-Surinamese and Dutch patients perceive and manage antihypertensive drug treatment: a qualitative study.

PubMed

Beune, Erik J A J; Haafkens, Joke A; Agyemang, Charles; Schuster, John S; Willems, Dick L

2008-04-01

To explore and compare how Ghanaian, African-Surinamese (Surinamese), and White-Dutch patients perceive and manage antihypertensive drug treatment in Amsterdam, the Netherlands. Qualitative study was conducted using detailed interviews with a purposive sample of 46 hypertensive patients without comorbidity who were prescribed antihypertensives. Patients in all the ethnic groups actively decided how to manage their prescribed antihypertensive regimens. In all the groups, confidence in the doctor and beneficial effects of medication were reasons for taking prescribed antihypertensive dosage. Particularly, ethnic-minority patients reported lowering or leaving off the prescribed medication dosage. Explanations for altering prescribed dosage comprised disliking chemical medications, fear of side effects and preference for alternative treatment. Surinamese and Ghanaian men also worried about the negative effects of antihypertensives on their sexual performance. Some Ghanaians mentioned fear of addiction or lack of money as explanations for altering prescribed dosage. Surinamese and Ghanaians often discontinued medication when visiting their homeland. Some respondents from all ethnic groups preferred natural treatments although treatment type varied. Patients' explanations for their decisions regarding the use of antihypertensives are often influenced by sociocultural issues and in ethnic-minority groups also by migration-related issues. Self-alteration of prescribed medication among Surinamese and Ghanaians may contribute to the low blood pressure (BP) control rate and high rate of malignant hypertension reported among these populations in the Netherlands. This study provides new information, which can help clinicians to understand how patients of diverse ethnic populations think about managing antihypertensive drug treatment and to address ethnic disparities in medication adherence and BP control.

Assessment and Management of Hypertension in Transplant Patients

PubMed Central

Burgess, Ellen D.; Cooper, James E.; Fenves, Andrew Z.; Goldsmith, David; McKay, Dianne; Mehrotra, Anita; Mitsnefes, Mark M.; Sica, Domenic A.; Taler, Sandra J.

2015-01-01

Hypertension in renal transplant recipients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular morbidity and mortality and shortened allograft survival are important consequences of inadequate control of hypertension. In this review, we examine the epidemiology, pathophysiology, and management considerations of post-transplant hypertension. Donor and recipient factors, acute and chronic allograft injury, and immunosuppressive medications may each explain some of the pathophysiology of post-transplant hypertension. As observed in other patient cohorts, renal artery stenosis and adrenal causes of hypertension may be important contributing factors. Notably, BP treatment goals for renal transplant recipients remain an enigma because there are no adequate randomized controlled trials to support a benefit from targeting lower BP levels on graft and patient survival. The potential for drug-drug interactions and altered pharmacokinetics and pharmacodynamics of the different antihypertensive medications need to be carefully considered. To date, no specific antihypertensive medications have been shown to be more effective than others at improving either patient or graft survival. Identifying the underlying pathophysiology and subsequent individualization of treatment goals are important for improving long-term patient and graft outcomes in these patients. PMID:25653099

Potential medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review

PubMed Central

Cheng, Shi-Hui; Barakatun-Nisak, Mohd Yusof; Anthony, Joseph; Ismail, Amin

2015-01-01

Cosmos caudatus is widely used as a traditional medicine in Southeast Asia. C. caudatus has been reported as a rich source of bioactive compounds such as ascorbic acid, quercetin, and chlorogenic acid. Studies have shown that C. caudatus exhibits high anti-oxidant capacity and various medicinal properties, including anti-diabetic activity, anti-hypertensive properties, anti-inflammatory responses, bone-protective effect, and anti-microbial activity. This review aims to present the potential medicinal benefits of C. caudatus from the available scientific literature. We searched PubMed and ScienceDirect database for articles published from 1995 to January 2015. Overall, 15 articles related to C. caudatus and its medicinal benefits are reviewed. All these studies demonstrated that C. caudatus is effective, having demonstrated its anti-diabetic, anti-hypertensive, anti-inflammatory, bone-protective, anti-microbial, and anti-fungal activity in both in vitro and animal studies. None of the studies showed any negative effect of C. caudatus related to medicinal use. Currently available evidence suggests that C. caudatus has beneficial effects such as reducing blood glucose, reducing blood pressure, promoting healthy bone formation, and demonstrating anti-inflammatory and anti-microbial properties. However, human clinical trial is warranted. PMID:26929767

Potential medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review.

PubMed

Cheng, Shi-Hui; Barakatun-Nisak, Mohd Yusof; Anthony, Joseph; Ismail, Amin

2015-10-01

Cosmos caudatus is widely used as a traditional medicine in Southeast Asia. C. caudatus has been reported as a rich source of bioactive compounds such as ascorbic acid, quercetin, and chlorogenic acid. Studies have shown that C. caudatus exhibits high anti-oxidant capacity and various medicinal properties, including anti-diabetic activity, anti-hypertensive properties, anti-inflammatory responses, bone-protective effect, and anti-microbial activity. This review aims to present the potential medicinal benefits of C. caudatus from the available scientific literature. We searched PubMed and ScienceDirect database for articles published from 1995 to January 2015. Overall, 15 articles related to C. caudatus and its medicinal benefits are reviewed. All these studies demonstrated that C. caudatus is effective, having demonstrated its anti-diabetic, anti-hypertensive, anti-inflammatory, bone-protective, anti-microbial, and anti-fungal activity in both in vitro and animal studies. None of the studies showed any negative effect of C. caudatus related to medicinal use. Currently available evidence suggests that C. caudatus has beneficial effects such as reducing blood glucose, reducing blood pressure, promoting healthy bone formation, and demonstrating anti-inflammatory and anti-microbial properties. However, human clinical trial is warranted.

Declining Risk of Sudden Death in Heart Failure.

PubMed

Shen, Li; Jhund, Pardeep S; Petrie, Mark C; Claggett, Brian L; Barlera, Simona; Cleland, John G F; Dargie, Henry J; Granger, Christopher B; Kjekshus, John; Køber, Lars; Latini, Roberto; Maggioni, Aldo P; Packer, Milton; Pitt, Bertram; Solomon, Scott D; Swedberg, Karl; Tavazzi, Luigi; Wikstrand, John; Zannad, Faiez; Zile, Michael R; McMurray, John J V

2017-07-06

The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail. We analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014. Patients who had an implantable cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization. Sudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause of heart failure and worse cardiac function, than those in whom sudden death did not occur. There was a 44% decline in the rate of sudden death across the trials (P=0.03). The cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in the most recent trial. The rate of sudden death was not higher among patients with a recent diagnosis of heart failure than among those with a longer-standing diagnosis. Rates of sudden death declined substantially over time among ambulatory patients with heart failure with reduced ejection fraction who were enrolled in clinical trials, a finding that is consistent with a cumulative benefit of evidence-based medications on this cause of death. (Funded by the China Scholarship Council and the University of Glasgow.).

Hypertensive Emergencies in Pregnancy.

PubMed

Olson-Chen, Courtney; Seligman, Neil S

2016-01-01

The prevalence of hypertensive disorders in pregnancy is increasing. The etiology and pathophysiology of hypertensive disorders in pregnancy remain poorly understood. Hypertensive disorders are a major cause of maternal and perinatal morbidity and mortality. Treatment of hypertension decreases the incidence of severe hypertension, but it does not impact rates of preeclampsia or other pregnancy complications. Several antihypertensive medications are commonly used in pregnancy, although there is a lack of randomized controlled trials. Severe hypertension should be treated immediately to prevent maternal end-organ damage. Appropriate antepartum, intrapartum, and postpartum management is important in caring for patients with hypertensive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

HYPERTENSION’S 3 DILEMMAS & 3 SOLUTIONS Pharmacology of the Kidney in Hypertension

PubMed Central

Pettinger, William

2017-01-01

SUMMARY The Hypertension Community has three conflicting dilemmas, a goal systolic pressure of 120 mmHg or less (The SPRINT Trials), 40% of our 60,000,000 hypertensives still sustain blood pressures above 140/90 mmHg and our most potent antihypertensive drug minoxidil sits on the side-lines, imprisoned in the FDA’s Black Box Designation. My solutions to these dilemmas are: #1. Review of the facts of our most potent antihypertensive drug minoxidil which is essentially free of toxicity, #2. Treatment focus on the fundamental cause of High Blood Pressure, excess dietary sodium and, #3. Prevention of, and/or reversal of, the fundamental mechanism of worsening hypertension, arteriolar hypertrophy. My focus at U.T. Southwestern in Dallas was on extremely severely hypertensive patients with a quantifiable, measurable complication of high blood pressure, progression of nephrosclerotic damage to kidneys. This model had the greatest likelihood of exposing fundamental dis-regulatory mechanisms in hypertensive patients (which it did) and the potential for study of the most relevant antihypertensive drug interactions to achieve optimal blood pressure control (which it did). By maintaining diastolic pressures at 80 mmHg or less in the first NIH supported, long term randomized clinical trial to save the kidneys, the bases for a fundamental blood pressure support mechanism (arteriolar hypertrophy) was illuminated but not fully described until now. This fundamental hypertensinogenic mechanism results from HBP but with time and severity, becomes its own raison d’être. I am now 84 years of age. As a result of a stroke 20 years ago which caused permanent double vision and because of poor blood pressure control with triple therapy I started using minoxidil 5 mg/day along with atenolol and occasional furosemide. Now, along with some dietary salt restriction, my resting blood pressure is 110/65–125/75 and, in spite of > 30 year history of HBP, I have no retinal arteriolar hypertrophy nor arcus senilis (Dr. Schwartz-U. of Miami) which is almost universally present at this age. YES, prevention of, or reversal of, arteriolar hypertrophy should be a central focus of HBP treatment. I simply wish to share a bit of accumulated wisdom that might be of use to others. PMID:28267687

Optimising the changing role of the community pharmacist: a randomised trial of the impact of audit and feedback

PubMed Central

Winslade, Nancy; Eguale, Tewodros; Tamblyn, Robyn

2016-01-01

Objective To evaluate the impact of comparative performance feedback to community pharmacists on provision of professional services and the quality of patients’ medication use. Design Randomised, controlled, single-blind trial. Setting All 1833 community pharmacies in the Quebec province, Canada. Participants 1814 pharmacies not opting out and with more than 5 dispensings of the target medications during the 6-month baseline were randomised by a 2×2 factorial design to feedback first for hypertension adherence (907 control, 907 intervention) followed by randomisation for asthma adherence (791 control, 807 intervention). 1422 of 1814 pharmacies had complete information available during the follow-up for hypertension intervention (706 intervention, 716 control), and 1301 of 1598 had the follow-up information for asthma (657 intervention, 644 control). Intervention Using provincial billing data to measure performance, mailed comparative feedback reported the pharmacy-level percentage of dispensings to patients non-adherent to antihypertensive medications or overusing asthma rescue inhalers. Primary and secondary outcome measures The number of hypertension/asthma services billed per pharmacy and percentage of dispensings to non-adherent patients over the 12 months post intervention. Results Feedback on the asthma measure led to increased provision of asthma services (control 0.2, intervention 0.4, RR 1.58, 95% CI 1.02 to 2.46). However, this did not translate into reductions in patients’ overuse of rescue inhalers (control 45.5%, intervention 44.6%, RR 0.99, 95% CI 0.98 to 1.01). For non-adherence to antihypertensive medications, feedback resulted in no difference in either provision of hypertension services (control 0.7, intervention 0.8, RR 1.25, 95% CI 0.86 to 1.82) or antihypertensive treatment adherence (control 27.9%, intervention 28.0%, RR 1.0, 95% CI 0.99 to 1.00). Baseline performance did not influence results, and there was no evidence of a cumulative effect with repeated feedback. Conclusions Comparative pharmacy performance feedback increased the provision of asthma pharmacists’ services but did not improve the performance on medication-use measures. Billing data can be used to evaluate the impact of billable services rendered by pharmacists on the quality of patients’ medication use. PMID:27207626

Bucindolol: A Pharmacogenomic Perspective on Its Use in Chronic Heart Failure

PubMed Central

Smart, Neil A.; Kwok, Nigel; Holland, David J.; Jayasighe, Rohan; Giallauria, Francesco

2011-01-01

Bucindolol is a non-selective β-adrenergic receptor blocker with α-1 blocker properties and mild intrinsic sympatholytic activity. The Beta-Blocker Evaluation of Survival Trial (BEST), which is the largest clinical trial of bucindolol in patients with heart failure, was terminated prematurely and failed to show an overall mortality benefit. However, benefits on cardiac mortality and re-hospitalization rates were observed in the BEST trial. Bucindolol has not shown benefits in African Americans, those with significantly low ejection fraction and those in NYHA class IV heart failure. These observations could be due to the exaggerated sympatholytic response to bucindolol in these sub-groups that may be mediated by genetic polymorphisms or changes in gene regulation due to advanced heart failure. This paper provides a timely clinical update on the use of bucindolol in chronic heart failure. PMID:21792345

Cost-Effectiveness of Implantable Pulmonary Artery Pressure Monitoring in Chronic Heart Failure.

PubMed

Sandhu, Alexander T; Goldhaber-Fiebert, Jeremy D; Owens, Douglas K; Turakhia, Mintu P; Kaiser, Daniel W; Heidenreich, Paul A

2016-05-01

This study aimed to evaluate the cost-effectiveness of the CardioMEMS (CardioMEMS Heart Failure System, St Jude Medical Inc, Atlanta, Georgia) device in patients with chronic heart failure. The CardioMEMS device, an implantable pulmonary artery pressure monitor, was shown to reduce hospitalizations for heart failure and improve quality of life in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial. We developed a Markov model to determine the hospitalization, survival, quality of life, cost, and incremental cost-effectiveness ratio of CardioMEMS implantation compared with usual care among a CHAMPION trial cohort of patients with heart failure. We obtained event rates and utilities from published trial data; we used costs from literature estimates and Medicare reimbursement data. We performed subgroup analyses of preserved and reduced ejection fraction and an exploratory analysis in a lower-risk cohort on the basis of the CHARM (Candesartan in Heart failure: Reduction in Mortality and Morbidity) trials. CardioMEMS reduced lifetime hospitalizations (2.18 vs. 3.12), increased quality-adjusted life-years (QALYs) (2.74 vs. 2.46), and increased costs ($176,648 vs. $156,569), thus yielding a cost of $71,462 per QALY gained and $48,054 per life-year gained. The cost per QALY gained was $82,301 in patients with reduced ejection fraction and $47,768 in those with preserved ejection fraction. In the lower-risk CHARM cohort, the device would need to reduce hospitalizations for heart failure by 41% to cost <$100,000 per QALY gained. The cost-effectiveness was most sensitive to the device's durability. In populations similar to that of the CHAMPION trial, the CardioMEMS device is cost-effective if the trial effectiveness is sustained over long periods. Post-marketing surveillance data on durability will further clarify its value. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Comparison of amlodipine versus other calcium channel blockers on blood pressure variability in hypertensive patients in China: a retrospective propensity score-matched analysis.

PubMed

Zhang, Lin; Yang, JinKui; Li, LanTing; Liu, DongDong; Xie, XiaoPing; Dong, Peng; Lin, Yong

2018-06-11

Reducing the fluctuation of blood pressure has recently been recognized as a potential target for improving management of hypertension to prevent cardiovascular events, particularly for strokes. Some randomized controlled trials demonstrated that amlodipine can effectively reduce blood pressure as a well-established, long-acting calcium channel blocker (CCB). However, few data are available for amlodipine on blood pressure variability (BPV) in China in a real-world setting. This study aimed to assess the effect of amlodipine versus other CCB antihypertensive agents on BPV. A retrospective propensity score-matched analysis was conducted, which retrieved the encounter data from 5582 hypertensive inpatients (with a median age of 69, female percentage of 48%, diastolic blood pressure ≥40 and <150 mmHg; systolic blood pressure (SBP) ≥70 mmHg and <260 mmHg), who had taken at least one antihypertensive agent and completed at least three SBP measurements during the visit. International Classification of Diseases was used to identify the hypertensive patients. BPV was calculated with standard deviation (SD) and coefficient of variation (CV) of SBP during a single inpatient visit. The Propensity Score Matching was used to balance the cohort of patients prescribed amlodipine or other CCBs. A series of appropriate statistical tests were applied to the propensity score-matched samples to examine the different effects on BPV. Additionally, the hypertensive patients with comorbidity such as coronary artery disease, diabetes mellitus, myocardial infarction, heart failure and chronic kidney disease were analyzed. For the hypertensive patients (n = 1756, for each cohort), patients prescribed amlodipine showed lower BPV than patients prescribed other CCBs (12.90 vs 13.76 mmHg, p < 0.05 [SD] and 9.47 vs 10.06, p < 0.05 [CV]). For the hypertensive patients with comorbidity (n = 1080, for each cohort), patients prescribed amlodipine had lower BPV than patients prescribed other CCBs as well (13.24 vs 14.23 mmHg, p < 0.05 [SD] and 9.66 vs 10.28, p < 0.05 [CV]). amlodipine was associated with lower BPV than other CCBs for both hypertensive patients and hypertensive patients with comorbidity.

Rate and predictors of treatment failure to all-oral HCV regimens outside clinical trials.

PubMed

Arias, Ana; Aguilera, Antonio; Soriano, Vicente; Benítez-Gutiérrez, Laura; Lledó, Gemma; Navarro, Daniel; Treviño, Ana; Otero, Esteban; Peña, José M; Cuervas-Mons, Valentín; de Mendoza, Carmen

2017-01-01

Cure rates above 90% have been reported in most Phase III clinical trials using distinct all-oral direct-acting antivirals (DAAs) in chronic hepatitis C patients. Preliminary results in real-world patients have confirmed this, although efficacy tends to be lower. All consecutive chronic hepatitis C patients treated with all-oral DAA regimens at three hepatitis clinics in Spain were retrospectively examined. Host and viral factors were tested as predictors of treatment failure. A total of 363 chronic hepatitis C patients had completed a course of all-oral DAA therapy outside clinical trials up to the end of 2015. All but 14 (4%) patients achieved sustained virological response. There were 10 failures that occurred after 12 weeks of sofosbuvir-ledipasvir, despite 5 of them being on ribavirin. All failures but one were relapses. The only patient with viral breakthrough selected NS5B L159F and NS5A Y93H. In multivariate analyses, only advanced liver fibrosis (Metavir F3-F4) and HIV coinfection were significantly associated with treatment failure. A trend towards lower response was seen for HCV genotype 4. Treatment failures outside clinical trials are roughly seen in 4% of chronic hepatitis C patients who complete a course of all-oral DAA therapy, resembling what is seen in registration trials. In our series, outcomes were not significantly influenced by ribavirin addition, IL28B polymorphisms, HCV genotype, high baseline HCV RNA or prior interferon failure. However, advanced liver fibrosis and HIV coinfection were significantly associated with treatment failure. Our findings support that there is still room for individualization of current DAA therapy.

Inovium Ovarian Rejuvenation Trials

ClinicalTrials.gov

2018-05-18

Perimenopausal Disorder; Menopause; Menopause, Premature; Menopause Related Conditions; Menopause Premature Symptomatic; Menopause Premature Asymptomatic; Premature Ovarian Failure; Premature Ovarian Failure, Familial; Premature Ovarian Failure 2A; Premature Ovarian Failure 3; Premature Ovarian Failure 4; Premature Ovarian Failure 1; Premature Ovarian Failure 5; Premature Ovarian Failure 6; Premature Ovarian Failure 7; Premature Ovarian Failure 9; Premature Ovarian Failure 8; Infertility; Infertility, Female; Infertility Unexplained

Postural Changes in Measures of Arterial Stiffness in Hypertensive Subjects on Antihypertensive Drug Therapy: A Prospective, Pilot Study.

PubMed

Sule, Ashish Anil; Jun, Du Qi; Cheong, Chin Yee

2017-06-01

Prospective study with a controlled arm to know if there are variations of measures of arterial stiffness with posture in subjects with hypertension on antihypertensive medications. We studied postural variations of measures of arterial stiffness in 21 subjects with diagnosed hypertension on antihypertensive medications and compared them with 21 normotensive subjects. All subjects underwent pulse-wave analysis on SphygmoCor in the morning between 8 am to 10 am initially in supine and then in sitting position after 3 minutes. Summary measures on demographics, and blood pressure characteristics at sitting and supine positions are obtained. Differences between characteristics at supine and sitting position are compared using nonparametric paired test of Wilcoxon signed-rank test. A value of p  < 0.05 was accepted as statistically significant. Antihypertensive medications decreased the supine aortic augmentation pressure (AAP) and augmentation index (AI) but not significantly. When subgroups of patients with antihypertensive treatment were analyzed, it was noted that angiotensin-converting enzyme inhibitor and angiotensin receptor blocker group (12) decreased AAP and AI significantly in supine position compared with patients on other antihypertensive medications (9) ( p -value 0.034 and 0.038, respectively). There was no significant difference in other groups of calcium channel blockers, β-blockers, or diuretics. However, in normotensive control arm, there was an increase in AAP and AI in the supine position. In hypertensive subjects, on antihypertensive, there was reduction in AAP and AI in supine position compared with those of normotensives. The significance of the decrease in AAP and AI in supine position on antihypertensive needs to be studied further.

Factors predicting incremental administration of antihypertensive boluses during deep brain stimulator placement for Parkinson's disease.

PubMed

Rajan, Shobana; Deogaonkar, Milind; Kaw, Roop; Nada, Eman Ms; Hernandez, Adrian V; Ebrahim, Zeyd; Avitsian, Rafi

2014-10-01

Hypertension is common in deep brain stimulator (DBS) placement predisposing to intracranial hemorrhage. This retrospective review evaluates factors predicting incremental antihypertensive use intraoperatively. Medical records of Parkinson's disease (PD) patients undergoing DBS procedure between 2008-2011 were reviewed after Institutional Review Board approval. Anesthesia medication, preoperative levodopa dose, age, preoperative use of antihypertensive medications, diabetes mellitus, anxiety, motor part of the Unified Parkinson's Disease Rating Scale score and PD duration were collected. Univariate and multivariate analysis was done between each patient characteristic and the number of antihypertensive boluses. From the 136 patients included 60 were hypertensive, of whom 32 were on angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), told to hold on the morning of surgery. Antihypertensive medications were given to 130 patients intraoperatively. Age (relative risk [RR] 1.01; 95% confidence interval [CI] 1.00-1.02; p=0.005), high Joint National Committee (JNC) class (p<0.0001), diabetes mellitus (RR 1.4; 95%CI 1.2-17; p<0.0001) and duration of PD >10 years (RR 1.2; 95%CI 1.1-1.3; p=0.001) were independent predictors for antihypertensive use. No difference was noted in the mean dose of levodopa (p=0.1) and levodopa equivalent dose (p=0.4) between the low (I/II) and high severity (III/IV) JNC groups. Addition of dexmedetomidine to propofol did not influence antihypertensive boluses required (p=0.38). Intraoperative hypertension during DBS surgery is associated with higher age group, hypertensive, diabetic patients and longer duration of PD. Withholding ACEI or ARB is an independent predictor of hypertension requiring more aggressive therapy. Levodopa withdrawal and choice of anesthetic agent is not associated with higher intraoperative antihypertensive medications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Imputing Observed Blood Pressure for Antihypertensive Treatment: Impact on Population and Genetic Analyses

PubMed Central

2014-01-01

BACKGROUND Elevated blood pressure (BP), a heritable risk factor for many age-related disorders, is commonly investigated in population and genetic studies, but antihypertensive use can confound study results. Routine methods to adjust for antihypertensives may not sufficiently account for newer treatment protocols (i.e., combination or multiple drug therapy) found in contemporary cohorts. METHODS We refined an existing method to impute unmedicated BP in individuals on antihypertensives by incorporating new treatment trends. We assessed BP and antihypertensive use in male twins (n = 1,237) from the Vietnam Era Twin Study of Aging: 36% reported antihypertensive use; 52% of those treated were on multiple drugs. RESULTS Estimated heritability was 0.43 (95% confidence interval (CI) = 0.20–0.50) and 0.44 (95% CI = 0.22–0.61) for measured systolic BP (SBP) and diastolic BP (DBP), respectively. We imputed BP for antihypertensives by 3 approaches: (i) addition of a fixed value of 10/5mm Hg to measured SBP/DBP; (ii) incremented addition of mm Hg to BP based on number of medications; and (iii) a refined approach adding mm Hg based on antihypertensive drug class and ethnicity. The imputations did not significantly affect estimated heritability of BP. However, use of our most refined imputation method and other methods resulted in significantly increased phenotypic correlations between BP and body mass index, a trait known to be correlated with BP. CONCLUSIONS This study highlights the potential usefulness of applying a representative adjustment for medication use, such as by considering drug class, ethnicity, and the combination of drugs when assessing the relationship between BP and risk factors. PMID:24532572

Blood Pressure, Antihypertensive Polypharmacy, Frailty, and Risk for Serious Fall Injuries Among Older Treated Adults With Hypertension.

PubMed

Bromfield, Samantha G; Ngameni, Cedric-Anthony; Colantonio, Lisandro D; Bowling, C Barrett; Shimbo, Daichi; Reynolds, Kristi; Safford, Monika M; Banach, Maciej; Toth, Peter P; Muntner, Paul

2017-08-01

Antihypertensive medication and low systolic blood pressure (BP) and diastolic BP have been associated with an increased falls risk in some studies. Many older adults have indicators of frailty, which may increase their risk for falls. We contrasted the association of systolic BP, diastolic BP, number of antihypertensive medication classes taken, and indicators of frailty with risk for serious fall injuries among 5236 REGARDS study (Reasons for Geographic and Racial Difference in Stroke) participants ≥65 years taking antihypertensive medication at baseline with Medicare fee-for-service coverage. Systolic BP and diastolic BP were measured, and antihypertensive medication classes being taken assessed through a pill bottle review during a study visit. Indicators of frailty included low body mass index, cognitive impairment, depressive symptoms, exhaustion, impaired mobility, and history of falls. Serious fall injuries were defined as fall-related fractures, brain injuries, or joint dislocations using Medicare claims through December 31, 2014. Over a median of 6.4 years, 802 (15.3%) participants had a serious fall injury. The multivariable-adjusted hazard ratio for a serious fall injury among participants with 1, 2, or ≥3 indicators of frailty versus no frailty indicators was 1.18 (95% confidence interval, 0.99-1.40), 1.49 (95% confidence interval, 1.19-1.87), and 2.04 (95% confidence interval, 1.56-2.67), respectively. Systolic BP, diastolic BP, and number of antihypertensive medication classes being taken at baseline were not associated with risk for serious fall injuries after multivariable adjustment. In conclusion, indicators of frailty, but not BP or number of antihypertensive medication classes, were associated with increased risk for serious fall injuries among older adults taking antihypertensive medication. © 2017 American Heart Association, Inc.

Biofilm inhibition of spoilage bacteria by Argentinean fruit juices with antihypertensive activity.

PubMed

Vallejo, Claudia V; Aredes-Fernández, Pedro A; Farías, Marta E; Rodríguez-Vaquero, María J

2013-01-01

Argentinean juices have been studied for their antihypertensive activity, the inhibition of bacteria biofilm formation and the effect on the viability of wine yeast. The influence of phenolic compounds on these activities was evaluated. These studies are the first step for the development of a new type of wine that includes grape must supplement with fruit juices with antihypertensive effect. All juices posses a high antihypertensive activity, higher than 50%. Strawberry juices and eureka lemon showed the highest activity, whereas clarified juices posses the lowest activity. All studied juices produce a high inhibition of bacteria biofilm formation, and the strawberry, orange and mandarin varieties not affect the growth or viability of yeast. Our results permit to conclude that it could be possible the use of these juices in a new type of wine or as a source of new antihypertensive agents for pharmaceutical industry.

Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial.

PubMed

Azizi, Michel; Sapoval, Marc; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Midulla, Marco; Mounier-Véhier, Claire; Courand, Pierre-Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Trillaud, Hervé; Pereira, Helena; Plouin, Pierre-François; Chatellier, Gilles

2015-05-16

Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups. In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation. French Ministry of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Issues in hypertension: drug tolerability and special populations.

PubMed

Gavras, H P

2001-07-01

Improvements in the death rate from coronary heart disease and in the control of hypertension have leveled off in recent years, reversing a trend toward steady improvement that began in 1972. Of the roughly 20% of Americans who suffer from hypertension, only 29% achieve adequate control (<140/90 mm Hg) with treatment and nearly half receive no treatment at all. Poor adherence to therapy doubtless plays a key role in this failure. As a major cause of poor adherence, tolerability becomes an extremely important element in any discussion of effective antihypertensive treatment. Despite their efficacy in treating hypertension, diuretics, beta-blockers, and calcium channel blockers have all been associated with numerous side effects, including increased serum lipid levels, insulin resistance, and edema. With the introduction of the angiotensin converting enzyme (ACE) inhibitors, patients were able to achieve blood pressure goals with fewer side effects. These agents, however, cause an irritating cough in up to 19% of patients. A newer class of drugs, the angiotensin receptor blockers (ARB), have similar effects to the ACE inhibitors, but their highly selective nature produces even fewer side effects. Eprosartan is a structurally unique ARB. Like the other ARB, this promising new agent has a side effect profile similar to placebo, and its response rate rivals or exceeds that of enalapril. Although it remains to be seen whether the ARB can significantly reduce morbidity and mortality from cardiovascular disease, preliminary data from the Evaluation of Losartan in the Elderly (ELITE) trial appear to be promising.

Renal Sympathetic Denervation in the Treatment of Resistant Hypertension

PubMed Central

Sánchez-Álvarez, Catalina; González-Vélez, Miguel; Stilp, Erik; Ward, Charisse; Mena-Hurtado, Carlos

2014-01-01

Arterial hypertension (HTN) is a major health problem worldwide. Treatment-resistant hypertension (trHTN) is defined as the failure to achieve target blood pressure despite the concomitant use of maximally tolerated doses of three different antihypertensive medications, including a diuretic. trHTN is associated with considerable morbidity and mortality. Renal sympathetic denervation (RDn) is available and implemented abroad as a strategy for the treatment of trHTN and is currently under clinical investigation in the United States. Selective renal sympathectomy via an endovascular approach effectively decreases renal sympathetic nerve hyperactivity leading to a decrease in blood pressure. The Symplicity catheter, currently under investigation in the United States, is a 6-French compatible system advanced under fluoroscopic guidance via percutaneous access of the common femoral artery to the distal lumen of each of the main renal arteries. Radiofrequency (RF) energy is then applied to the endoluminal surface of the renal arteries via an electrode located at the tip of the catheter. Two clinical trials (Symplicity HTN 1 and Symplicity HTN 2) have shown the efficacy of RDn with a post-procedure decline of 27/17mmHg at 12 months and 32/12 mmHg at 6 months, respectively, with few minor adverse events. Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study currently under way and will provide further insights about the safety and efficacy of renal denervation in patients with trHTN. PMID:25506285

Diuretics for heart failure.

PubMed

Faris, Rajaa F; Flather, Marcus; Purcell, Henry; Poole-Wilson, Philip A; Coats, Andrew J S

2012-02-15

Chronic heart failure is a major cause of morbidity and mortality worldwide. Diuretics are regarded as the first-line treatment for patients with congestive heart failure since they provide symptomatic relief. The effects of diuretics on disease progression and survival remain unclear. To assess the harms and benefits of diuretics for chronic heart failure Updated searches were run in the Cochrane Central Register of Controlled Trials in The Cochrane Library (CENTRAL Issue 1 of 4, 2011), MEDLINE (1966 to 22 February 2011), EMBASE (1980 to 2011 Week 07) and HERDIN database (1990 to February 2011). We hand searched pertinent journals and reference lists of papers were inspected. We also contacted manufacturers and researchers in the field. No language restrictions were applied. Double-blinded randomised controlled trials of diuretic therapy comparing one diuretic with placebo, or one diuretic with another active agent (e.g. ACE inhibitors, digoxin) in patients with chronic heart failure. Two authors independently abstracted the data and assessed the eligibility and methodological quality of each trial. Extracted data were analysed by determining the odds ratio for dichotomous data, and difference in means for continuous data, of the treated group compared with controls. The likelihood of heterogeneity of the study population was assessed by the Chi-square test. If there was no evidence of statistical heterogeneity and pooling of results was clinically appropriate, a combined estimate was obtained using the fixed-effects model. This update has not identified any new studies for inclusion. The review includes 14 trials (525 participants), 7 were placebo-controlled, and 7 compared diuretics against other agents such as ACE inhibitors or digoxin. We analysed the data for mortality and for worsening heart failure. Mortality data were available in 3 of the placebo-controlled trials (202 participants). Mortality was lower for participants treated with diuretics than for placebo, odds ratio (OR) for death 0.24, 95% confidence interval (CI) 0.07 to 0.83; P = 0.02. Admission for worsening heart failure was reduced in those taking diuretics in two trials (169 participants), OR 0.07 (95% CI 0.01 to 0.52; P = 0.01). In four trials comparing diuretics to active control (91 participants), diuretics improved exercise capacity in participants with CHF, difference in means WMD 0.72 , 95% CI 0.40 to 1.04; P < 0.0001. The available data from several small trials show that in patients with chronic heart failure, conventional diuretics appear to reduce the risk of death and worsening heart failure compared to placebo. Compared to active control, diuretics appear to improve exercise capacity.

Clinical trials update from the Heart Failure Society of America: EMOTE, HERB-CHF, BEST genetic sub-study and RHYTHM-ICD.

PubMed

Lalukota, Krishna; Cleland, John G F; Ingle, Lee; Clark, Andrew L; Coletta, Alison P

2004-12-01

This article summarises key presentations relevant to the pathophysiology, prevention or treatment of heart failure, from the Heart Failure Society of America annual meeting held in Toronto, Canada. Data from the EnoxiMone in intravenous inOTropE-dependent subjects (EMOTE) study suggest that the oral PDE-3 inhibitor enoximone may be effective for weaning severe heart failure patients from intravenous inotropic therapy. Hawthorn Extract Randomised Blinded Trial in CHF (HERB-CHF) failed to show a benefit of hawthorn extract added to conventional heart failure therapy. A genetic sub-group analysis of the Blocker Evaluation of Survival Trial (BEST) study showed that bucindolol reduced mortality and hospitalisations in patients who were homozygous for the Arg389 variant of the beta(1) adrenoceptor. In the Resynchronisation Hemodynamic Treatment for Heart Failure Management (RHYTHM-ICD) study, patients randomised to cardiac resynchronisation therapy (CRT) showed an improvement in symptoms and functional capacity compared to the control group.

The effect of different antihypertensive drugs on cavernous tissue in experimental chronic renal insufficiency.

PubMed

Toblli, Jorge E; Stella, Inés; Mazza, Osvaldo N; Ferder, León; Inserra, Felipe

2006-01-01

Male erectile dysfunction increases in prevalence in patients with severe chronic renal failure. Since arterial hypertension induces significant damage in cavernous tissue (CT), and considering that hypertension is extremely common in patients with end-stage renal disease (ESRD), the aim of this study was to evaluate the effect of the most conventionally employed antihypertensive drugs on CT in a rat model of renal insufficiency. Five groups of male rats with subtotal nephrectomy (STNx) and 1 with sham operations were studied over 6 months: STNx without treatment, STNx with benazepril (BZ), STNx with losartan (LS), STNx with amlodipine (AML) and STNx with atenolol (AT) plus the sham group. All rats were sacrificed at 6 months after STNx, and penises processed for LM and immunohistochemical studies. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries and the amount of collagen type III were evaluated. All groups with antihypertensive drugs showed similar control in blood pressure throughout the study. Un-treated STNx, STNx with AML and STNx with AT presented significant (p<0.01) hypertrophy in both VSM and CSM, together with an increased amount of collagen type III in CT. Conversely, STNx with either BZ or LS showed a substantial (p<0.01) reduction in all of these variables, with values not different from the sham group. There was a significant (p<0.01) negative correlation between creatinine clearance and the amount of VSM, CSM and collagen type III deposition in CT in untreated STNx, STNx with AML and STNx with AT, but not in STNx with BZ, STNx with LS and sham. These results suggest that the interactions against the renin-angiotensin system (RAS) either by ACE inhibitors or angiotensin AT1 receptor blockers produce considerable benefits regarding structural abnormalities in CT in this animal model of renal insufficiency beyond blood pressure control.

Hawthorn

MedlinePlus

... in patients with heart failure: the SPICE trial. European Journal of Heart Failure. 2008;10(12):1255-1263. ... with mild to moderate symptoms of heart failure . European Journal of Heart Failure. 2008;10(6):587-593. ...

A Markov chain model for reliability growth and decay

NASA Technical Reports Server (NTRS)

Siegrist, K.

1982-01-01

A mathematical model is developed to describe a complex system undergoing a sequence of trials in which there is interaction between the internal states of the system and the outcomes of the trials. For example, the model might describe a system undergoing testing that is redesigned after each failure. The basic assumptions for the model are that the state of the system after a trial depends probabilistically only on the state before the trial and on the outcome of the trial and that the outcome of a trial depends probabilistically only on the state of the system before the trial. It is shown that under these basic assumptions, the successive states form a Markov chain and the successive states and outcomes jointly form a Markov chain. General results are obtained for the transition probabilities, steady-state distributions, etc. A special case studied in detail describes a system that has two possible state ('repaired' and 'unrepaired') undergoing trials that have three possible outcomes ('inherent failure', 'assignable-cause' 'failure' and 'success'). For this model, the reliability function is computed explicitly and an optimal repair policy is obtained.

[Failure mode and effects analysis to improve quality in clinical trials].

PubMed

Mañes-Sevilla, M; Marzal-Alfaro, M B; Romero Jiménez, R; Herranz-Alonso, A; Sanchez Fresneda, M N; Benedi Gonzalez, J; Sanjurjo-Sáez, M

The failure mode and effects analysis (FMEA) has been used as a tool in risk management and quality improvement. The objective of this study is to identify the weaknesses in processes in the clinical trials area, of a Pharmacy Department (PD) with great research activity, in order to improve the safety of the usual procedures. A multidisciplinary team was created to analyse each of the critical points, identified as possible failure modes, in the development of clinical trial in the PD. For each failure mode, the possible cause and effect were identified, criticality was calculated using the risk priority number and the possible corrective actions were discussed. Six sub-processes were defined in the development of the clinical trials in PD. The FMEA identified 67 failure modes, being the dispensing and prescription/validation sub-processes the most likely to generate errors. All the improvement actions established in the AMFE were implemented in the Clinical Trials area. The FMEA is a useful tool in proactive risk management because it allows us to identify where we are making mistakes and analyze the causes that originate them, to prioritize and to adopt solutions to risk reduction. The FMEA improves process safety and quality in PD. Copyright © 2018 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial.

PubMed

Piccini, Jonathan P; Connolly, Stuart J; Abraham, William T; Healey, Jeff S; Steinberg, Benjamin A; Al-Khalidi, Hussein R; Dignacco, Patricia; van Veldhuisen, Dirk J; Sauer, William H; White, Michel; Wilton, Stephen B; Anand, Inder S; Dufton, Christopher; Marshall, Debra A; Aleong, Ryan G; Davis, Gordon W; Clark, Richard L; Emery, Laura L; Bristow, Michael R

2018-05-01

Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded "seamless" phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501). Copyright © 2017 Elsevier Inc. All rights reserved.

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

PubMed

Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

2016-07-01

Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

PubMed

Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

2016-04-01

Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

Access to antihypertensive agents in Brazil: evaluation of the "health has no price" program.

PubMed

Araujo, João Leopoldo Oliveira; Pereira, Mariana Donato; de Sá Del Fiol, Fernando; Barberato-Filho, Silvio

2014-08-01

This article aims to evaluate access to antihypertensive agents during the first year of the "Health Has No Price" Program (Saúde Não Tem Preço [SNTP]) in Brazil. A longitudinal and observational study was performed based on the number of antihypertensive medications supplied in 55,000 private pharmacies distributed throughout the Brazilian territory during the period February 1, 2010, through January 31, 2012. The number of antihypertensive pills supplied in the first 12 months of the SNTP Program was compared with the number of pills supplied in the 12 months before its implementation. Six antihypertensive medicines showed an increase between 32% and 120% in the number of pills supplied in the first year of the program. In this same period, the growth of the Brazilian pharmaceutical market was ~13%. Additionally, 11 medicines containing the same active ingredients as the antihypertensive agents in the SNTP Program, but at concentrations not available for free, were analyzed; it was found that none showed a change >8%, and 5 showed a reduction in the number of pills supplied after the implementation of the SNTP Program. The analysis of 7 fixed-dose combinations not available in the SNTP Program that were formulated with the same active ingredients showed a change below the annual percentage growth of the Brazilian pharmaceutical market. The SNTP Program may have contributed to increased access to antihypertensive medicines in Brazil. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Arterial hypertension after age 65: from epidemiology and pathophysiology to therapy Do we know where we stand?

PubMed

Gąsowski, Jerzy; Piotrowicz, Karolina; Messerli, Franz H

2018-01-01

Arterial hypertension is a prevalent disease with great harming potential. After the age of 55 years the remaining lifetime risk of hypertension amounts to 90%. Despite the constant advances some important issues such as the cut-off blood pressure for the initiation of antihypertensive therapy or the therapeutic goal are debated. In this review, we present - based on the available literature - the current concepts concerning the pathophysiology, epi-demiology and antihypertensive therapy in patients aged 65 years or older. The pathophysiology of hypertension in older patients in principle rests on stiffening of large conduit arteries, which leads to greater systolic and lower diastolic blood pressure. This in most older patients results in isolated systolic hypertension. Additionally most of these patients have low-renin hypertension. Data from large-scale clinical trials indicate that therapy of such individuals with thiazide-like diuretics and long-acting dihydropiridine calcium channel blockers as first-line medications reduces risk of complications. Based on results of recently published trials, meta-analyses, and prospective observations, the optimal on-treatment blood pressure values for most older hypertensive patients should be set within the 130-139 mmHg range. At present, lower values of standard office blood pressure in this group of patients have not been shown to be associ-ated with additional benefits, and may be associated with a greater risk of adverse events. In conclusion, we recommend that for most patients aged 65 years or more, standard office systolic blood pressure should be cautiously reduced to within 140 and 130 mmHg, preferably with a thiazide-like diuretic, long acting dihydropiridine calcium channel blocker or their combination.

Intensive systolic blood pressure control and incident chronic kidney disease in people with and without diabetes mellitus: secondary analyses of two randomised controlled trials.

PubMed

Beddhu, Srinivasan; Greene, Tom; Boucher, Robert; Cushman, William C; Wei, Guo; Stoddard, Gregory; Ix, Joachim H; Chonchol, Michel; Kramer, Holly; Cheung, Alfred K; Kimmel, Paul L; Whelton, Paul K; Chertow, Glenn M

2018-07-01

Guidelines, including the 2017 American College of Cardiology and American Heart Association blood pressure guideline, recommend tighter control of systolic blood pressure in people with type 2 diabetes. However, it is unclear whether intensive lowering of systolic blood pressure increases the incidence of chronic kidney disease in this population. We aimed to compare the effects of intensive systolic blood pressure control on incident chronic kidney disease in people with and without type 2 diabetes. The Systolic Blood Pressure Intervention Trial (SPRINT) tested the effects of a systolic blood pressure goal of less than 120 mm Hg (intensive intervention) versus a goal of less than 140 mm Hg (standard intervention) in people without diabetes. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial tested a similar systolic blood pressure intervention in people with type 2 diabetes. Our study is a secondary analysis of limited access datasets from SPRINT and the ACCORD trial obtained from the National Institutes of Health. In participants without chronic kidney disease at baseline (n=4311 in the ACCORD trial; n=6715 in SPRINT), we related systolic blood pressure interventions (intensive vs standard) to incident chronic kidney disease (defined as >30% decrease in estimated glomerular filtration rate [eGFR] to <60 mL/min per 1·73 m 2 ). These trials are registered with ClinicalTrials.gov, numbers NCT01206062 (SPRINT) and NCT00000620 (ACCORD trial). The average difference in systolic blood pressure between intensive and standard interventions was 13·9 mm Hg (95% CI 13·4-14·4) in the ACCORD trial and 15·2 mm Hg (14·8-15·6) in SPRINT. At 3 years, the cumulative incidence of chronic kidney disease in the ACCORD trial was 10·0% (95% CI 8·8-11·4) with the intensive intervention and 4·1% (3·3-5·1) with the standard intervention (absolute risk difference 5·9%, 95% CI 4·3-7·5). Corresponding values in SPRINT were 3·5% (95% CI 2·9-4·2) and 1·0% (0·7-1·4; absolute risk difference 2·5%, 95% CI 1·8-3·2). The absolute risk difference was significantly higher in the ACCORD trial than in SPRINT (p=0·0001 for interaction). Intensive lowering of systolic blood pressure increased the risk of incident chronic kidney disease in people with and without type 2 diabetes. However, the absolute risk of incident chronic kidney disease was higher in people with type 2 diabetes. Our findings suggest the need for vigilance in monitoring kidney function during intensive antihypertensive drug treatment, particularly in adults with diabetes. Long-term studies are needed to understand the clinical implications of antihypertensive treatment-related reductions in eGFR. National Institutes of Health. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed Central

2012-01-01

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

Systolic Blood Pressure and Incident Heart Failure in the Elderly

PubMed Central

Butler, Javed; Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Bibbins-Domingo, Kirsten; Najjar, Samer S.; Sutton-Tyrrell, Kim C.; Harris, Tamara B.; Kritchevsky, Stephen B.; Lloyd-Jones, Donald M.; Newman, Anne B.; Psaty, Bruce M.

2013-01-01

Objectives The exact form of the association between systolic blood pressure (SBP) and heart failure (HF) risk in the elderly remains incompletely defined, especially in individuals not receiving antihypertensive medications. Our aim was to examine the association between SBP and HF risk in the elderly. Design Competing-risks proportional hazards modeling of incident HF risk, utilizing 10-year follow-up data from two NIH-sponsored cohort studies; the Cardiovascular Health Study (inception: 1989-90 and 1992-93) and the Health ABC Study (inception: 1997-98). Setting Community-based cohorts. Participants 4408 participants (age, 72.8 [4.9] years; 53.1% women, 81.7% white; 18.3% black) without prevalent HF and not receiving antihypertensive medications at baseline. Main outcome measures Incident HF, defined as first adjudicated hospitalisation for HF. Results Over 10 years, 493 (11.1%) participants developed HF. Prehypertension (120-139 mmHg), stage 1 (140-159 mmHg), and stage 2 (≥160 mmHg) hypertension were associated with escalating HF risk; hazard ratios vs. optimal SBP (<120 mmHg) in competing-risks models controlling for clinical characteristics were 1.63 (95% CI, 1.23-2.16; P=0.001), 2.21 (95% CI, 1.65-2.96; P<0.001), and 2.60 (95% CI, 1.85-364; P<0.001), respectively. Overall 255 of 493 (51.7%) HF events occurred in participants with SBP <140 mm Hg at baseline. Increasing SBP was associated with higher HF risk in women than men; no race-SBP interaction was observed. In analyses with continuous SBP, HF risk had a continuous positive association with SBP to levels as low as 113 mmHg in men and 112 mmHg in women. Conclusions There is a continuous positive association between SBP and HF risk in the elderly for levels of SBP as low as <115 mmHg; over half of incident HF events occur in individuals with SBP <140 mmHg. PMID:21636845

The Impact of Worsening Heart Failure in the United States

PubMed Central

Cooper, Lauren B.; DeVore, Adam D.; Felker, G. Michael

2015-01-01

Synopsis In-hospital worsening heart failure represents a clinical scenario in which a patient hospitalized for treatment of acute heart failure experiences a worsening of their condition while in the hospital, requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and post-discharge outcomes. In-hospital worsening heart failure is increasingly being used as an endpoint, or as part of a combined endpoint, in many clinical trials in acute heart failure. This endpoint has advantages over other endpoints commonly used in acute and chronic heart failure trials, such as dyspnea relief and mortality or rehospitalization. Despite the extensive study of this condition, no treatment strategies have been approved for the prevention of this condition. However, several prediction models have been developed to identify worsening heart failure. Continued study in this area is warranted. PMID:26462100

When should we use nitrates in congestive heart failure?

PubMed

Vizzardi, Enrico; Bonadei, Ivano; Rovetta, Riccardo; D'Aloia, Antonio; Quinzani, Filippo; Curnis, Antonio; Dei Cas, Livio

2013-02-01

Organic nitrates remain among the oldest and most commonly employed drugs in cardiology. Although, in most cases, their use in acute and chronic heart failure is based on clinical practice, only a few clinical trials have been conducted to evaluate their use in acute and chronic heart failure, most of which compare them with other drugs to evaluate differing endpoints. The purpose of this review is to examine the various trials that have evaluated the use of nitrates in acute and chronic heart failure. © 2012 Blackwell Publishing Ltd.

Foundations of Pharmacotherapy for Heart Failure With Reduced Ejection Fraction: Evidence Meets Practice, Part II.

PubMed

McIlvennan, Colleen K; Page, Robert L

Pharmacologic treatment for systolic heart failure, otherwise known as heart failure with reduced ejection fraction, has been established through clinical trials and is formulated into guidelines to standardize the diagnosis and treatment. Since the introduction of angiotensin-converting enzyme inhibitors and vasodilators in the 1980s, many guideline-recommended therapies have emerged over the past 20 years targeting specific neurohormones, aldosterone, and catecholamines to treat heart failure. Part 2 of this series will describe β-blockers, digoxin, and aldosterone antagonists in the context of the mechanism of action in heart failure, investigational trials that showed beneficial effects, and the practical applications for clinical use.

Prediction of cardiovascular outcome by estimated glomerular filtration rate and estimated creatinine clearance in the high-risk hypertension population of the VALUE trial.

PubMed

Ruilope, Luis M; Zanchetti, Alberto; Julius, Stevo; McInnes, Gordon T; Segura, Julian; Stolt, Pelle; Hua, Tsushung A; Weber, Michael A; Jamerson, Ken

2007-07-01

Reduced renal function is predictive of poor cardiovascular outcomes but the predictive value of different measures of renal function is uncertain. We compared the value of estimated creatinine clearance, using the Cockcroft-Gault formula, with that of estimated glomerular filtration rate (GFR), using the Modification of Diet in Renal Disease (MDRD) formula, as predictors of cardiovascular outcome in 15 245 high-risk hypertensive participants in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. For the primary end-point, the three secondary end-points and for all-cause death, outcomes were compared for individuals with baseline estimated creatinine clearance and estimated GFR < 60 ml/min and > or = 60 ml/min using hazard ratios and 95% confidence intervals. Coronary heart disease, left ventricular hypertrophy, age, sex and treatment effects were included as covariates in the model. For each end-point considered, the risk in individuals with poor renal function at baseline was greater than in those with better renal function. Estimated creatinine clearance (Cockcroft-Gault) was significantly predictive only of all-cause death [hazard ratio = 1.223, 95% confidence interval (CI) = 1.076-1.390; P = 0.0021] whereas estimated GFR was predictive of all outcomes except stroke. Hazard ratios (95% CIs) for estimated GFR were: primary cardiac end-point, 1.497 (1.332-1.682), P < 0.0001; myocardial infarction, 1.501 (1.254-1.796), P < 0.0001; congestive heart failure, 1.699 (1.435-2.013), P < 0.0001; stroke, 1.152 (0.952-1.394) P = 0.1452; and all-cause death, 1.231 (1.098-1.380), P = 0.0004. These results indicate that estimated glomerular filtration rate calculated with the MDRD formula is more informative than estimated creatinine clearance (Cockcroft-Gault) in the prediction of cardiovascular outcomes.

Stenting and medical therapy for atherosclerotic renal-artery stenosis.

PubMed

Cooper, Christopher J; Murphy, Timothy P; Cutlip, Donald E; Jamerson, Kenneth; Henrich, William; Reid, Diane M; Cohen, David J; Matsumoto, Alan H; Steffes, Michael; Jaff, Michael R; Prince, Martin R; Lewis, Eldrin F; Tuttle, Katherine R; Shapiro, Joseph I; Rundback, John H; Massaro, Joseph M; D'Agostino, Ralph B; Dworkin, Lance D

2014-01-02

Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03). Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.).

Comparison of Measured GFR, Serum Creatinine, Cystatin C, and Beta-Trace Protein to Predict ESRD in African Americans With Hypertensive CKD

PubMed Central

Bhavsar, Nrupen A.; Appel, Lawrence J.; Kusek, John W.; Contreras, Gabriel; Bakris, George; Coresh, Josef; Astor, Brad C.

2011-01-01

Background Identification of persons with chronic kidney disease (CKD) who are at highest risk to progress to end stage renal disease (ESRD) is necessary to reduce the burden of kidney failure. The relative utility of traditional markers of kidney function, including estimated glomerular filtration rate (GFR) and serum creatinine, and emerging markers of kidney function, including cystatin C and beta-trace protein (BTP), to predict ESRD and mortality has yet to be established. Study Design Randomized clinical trial followed by an observational cohort study. Setting & Participants 865 African American individuals with hypertensive CKD enrolled in a clinical trial of two levels of blood pressure control and three different antihypertensive drugs as initial therapy and subsequently followed by an observational cohort study. Predictors Quintile of measured GFR (mGFR) by iothalamate clearance, serum creatinine, serum creatinine-based estimated GFR (eGFRSCr), cystatin C, and BTP. Outcomes and Measurements Incidence of ESRD and mortality. Results A total of 246 participants reached ESRD over a median follow-up of 102 months. The incidence rate of ESRD was higher with higher quintiles of each marker. The association between higher BTP and ESRD was stronger than those for the other markers, including mGFR. All the markers remained significantly associated with ESRD after adjustment for mGFR and relevant covariates (all p<0.05), with BTP retaining the strongest association (HR for highest versus lowest quintile, 5.7; 95% CI, 2.2-14.9). Associations with the combined endpoint of ESRD or mortality (n=390) were weaker, but remained significant for cystatin C (p=0.05) and BTP (p=0.004). Limitations The ability of these markers to predict ESRD and mortality in other racial and ethnic groups and among individuals with CKD due to other causes is unknown. Conclusions Plasma BTP and cystatin C may be useful adjuncts to serum creatinine and mGFR in evaluating risk for progression of kidney disease. PMID:21944667

Long-Term Renal and Cardiovascular Outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Participants by Baseline Estimated GFR

PubMed Central

Rahman, Mahboob; Cutler, Jeffrey A.; Davis, Barry R.; Piller, Linda B.; Whelton, Paul K.; Wright, Jackson T.; Barzilay, Joshua I.; Brown, Clinton D.; Colon, Pedro J.; Fine, Lawrence J.; Grimm, Richard H.; Gupta, Alok K.; Baimbridge, Charles; Haywood, L. Julian; Henriquez, Mario A.; Ilamaythi, Ekambaram; Oparil, Suzanne; Preston, Richard

2012-01-01

Summary Background and objectives CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone. Design, setting, participants, & measurements This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged ≥55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4–8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m2) as follows: normal/increased (≥90; n=8027), mild reduction (60–89; n=17,778), and moderate/severe reduction (<60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD. Results After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P<0.001). In participants with an eGFR <60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD. Conclusions CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD. PMID:22490878

Antihypertensive drug prescription trends at the primary health care centres in Bahrain.

PubMed

Jassim al Khaja, K A; Sequeira, R P; Wahab, A W; Mathur, V S

2001-05-01

To determine the antihypertensive drug prescribing pattern by primary care physicians in patients with uncomplicated essential hypertension; to identify whether such pattern of prescription is appropriate and in accordance with international guidelines for pharmacotherapy of hypertension; and to estimate the impact of such prescriptions on cost of treatment. A prescription-based survey among patients with uncomplicated essential hypertension was conducted in seven out of a total of 18 health centres in Bahrain. The relevant data for our study was collected using cards, designed for chronically-ill patients. A total of 1019 male and 1395 female (62.9%) out of 3838 of the study population were on monotherapy, whereas 596 male and 828 female (37.1%) were on antihypertensive combination therapy. Among the monotherapy category, the various antihypertensive drugs used were as follows: beta-blockers (58.8%), angiotensin converting enzyme (ACE) inhibitors (14.2%), calcium channel blockers (11.1%), diuretics (8.1%) and alpha-methyldopa (7.0%). With respect to overall utilization pattern, beta-blockers were the most frequently prescribed (65.5%), diuretics ranked second (27.4%), followed by ACE inhibitors (20.6%), calcium channel blockers (19.9%) and alpha-methyldopa (8.5%). Within each class of antihypertensives used, the most frequently used individual agents were as follows: (a) among beta-blockers 97.7% used atenolol; (b) among the diuretics, indapamide (35.4%), hydrochlorothiazide (HCTZ) (32.7%), HCTZ in combination with triamterene (25.7%), and chlorthalidone (4.6%); (c) among the ACE inhibitors, captopril (44.9%), enalapril (29.7%), and lisinopril (19.0%); (d) among the calcium channel blockers, nifedipine (98.2%). Significant age- and gender-related differences in prescribing patterns were seen. Short-acting nifedipine monotherapy was inappropriately prescribed in a significant number of patients above the age of 50 years. ACE inhibitors accounted for approximately two-thirds of the total antihypertensive drug expenditure, although these drugs represent only one-fifth of overall antihypertensives used. There is a trend towards excessive use of expensive thiazide-like diuretics such as indapamide which seems to be unjustifiable practice, particularly in a study population free from diabetic hypertensive patients. The general pattern of antihypertensive utilization appears to be in accordance with the guidelines of WHO and the Joint National Committee issued in the 1990s. The trends of prescribing of antihypertensives were in favour of conventional ones such as the beta blockers and diuretics, and the introduction of newer classes of antihypertensives had a generally minimal impact on the prescribing profile. Almost two-thirds of the patients were treated with monotherapy. A disproportionately large percentage of antihypertensive drug cost was due to overt use of ACE inhibitors, and indapamide, instead of thiazide diuretics. The use of short-acting calcium channel blockers especially in the elderly is unjustifiable.

Do Bayesian adaptive trials offer advantages for comparative effectiveness research? Protocol for the RE-ADAPT study

PubMed Central

Luce, Bryan R; Broglio, Kristine R; Ishak, K Jack; Mullins, C Daniel; Vanness, David J; Fleurence, Rachael; Saunders, Elijah; Davis, Barry R

2013-01-01

Background Randomized clinical trials, particularly for comparative effectiveness research (CER), are frequently criticized for being overly restrictive or untimely for health-care decision making. Purpose Our prospectively designed REsearch in ADAptive methods for Pragmatic Trials (RE-ADAPT) study is a ‘proof of concept’ to stimulate investment in Bayesian adaptive designs for future CER trials. Methods We will assess whether Bayesian adaptive designs offer potential efficiencies in CER by simulating a re-execution of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study using actual data from ALLHAT. Results We prospectively define seven alternate designs consisting of various combinations of arm dropping, adaptive randomization, and early stopping and describe how these designs will be compared to the original ALLHAT design. We identify the one particular design that would have been executed, which incorporates early stopping and information-based adaptive randomization. Limitations While the simulation realistically emulates patient enrollment, interim analyses, and adaptive changes to design, it cannot incorporate key features like the involvement of data monitoring committee in making decisions about adaptive changes. Conclusion This article describes our analytic approach for RE-ADAPT. The next stage of the project is to conduct the re-execution analyses using the seven prespecified designs and the original ALLHAT data. PMID:23983160

Renal denervation therapy for hypertension: pathways for moving development forward.

PubMed

White, William B; Galis, Zorina S; Henegar, Jeffrey; Kandzari, David E; Victor, Ronald; Sica, Domenic; Townsend, Raymond R; Turner, J Rick; Virmani, Renu; Mauri, Laura

2015-05-01

This scientific statement provides a summary of presentations and discussions at a cardiovascular Think Tank co-sponsored by the American Society of Hypertension (ASH), the United States Food and Drug Administration (FDA), and the National Heart, Lung, and Blood Institute (NHLBI) held in North Bethesda, Maryland, on June 26, 2014. Studies of device therapies for the treatment of hypertension are requested by regulators to evaluate their safety and efficacy during their development programs. Think Tank participants thought that important considerations in undertaking such studies were: (1) Preclinical assessment: how likely it is that both efficacy and safety data indicating benefit in humans will be obtained, and/or whether a plausible mechanism of action for efficacy can be identified; (2) Early human trial(s): the ability to determine that the device has an acceptable benefit-to-risk balance for its use in the intended patient population and without the influence of drug therapy during a short-term follow-up period; and (3) Pivotal Phase III trial(s): the ability to prove the effectiveness of the device in a broad population in which the trial can be made as non-confounded as possible while still allowing for the determination for benefits when added to antihypertensive therapies. Copyright © 2015 American Society of Hypertension. All rights reserved.

The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial): study protocol

PubMed Central

2014-01-01

Background Insertion of a ventriculoperitoneal shunt (VPS) for the treatment of hydrocephalus is one of the most common neurosurgical procedures in the UK, but failures caused by infection occur in approximately 8% of primary cases. VPS infection is associated with considerable morbidity and mortality and its management results in substantial cost to the health service. Antibiotic-impregnated (rifampicin and clindamycin) and silver-impregnated VPS have been developed to reduce infection rates. Whilst there is some evidence showing that such devices may lead to a reduction in VPS infection, there are no randomised controlled trials (RCTs) to support their routine use. Methods/design Overall, 1,200 patients will be recruited from 17 regional neurosurgical units in the UK and Ireland. Patients of any age undergoing insertion of their first VPS are eligible. Patients with previous indwelling VPS, active and on-going cerebrospinal fluid (CSF) or peritoneal infection, multiloculated hydrocephalus requiring multiple VPS or neuroendoscopy, and ventriculoatrial or ventriculopleural shunt planned will be excluded. Patients will be randomised 1:1:1 to either standard silicone (comparator), antibiotic-impregnated, or silver-impregnated VPS. The primary outcome measure is time to VPS infection. Secondary outcome measures include time to VPS failure of any cause, reason for VPS failure (infection, mechanical failure, or patient failure), types of bacterial VPS infection (organism type and antibiotic resistance), and incremental cost per VPS failure averted. Discussion The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial) is the first multi-centre RCT designed to determine whether antibiotic or silver-impregnated VPS reduce early shunt infection compared to standard silicone VPS. The results of this study will be used to inform current neurosurgical practice and may potentially benefit patients undergoing shunt surgery in the future. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN49474281. PMID:24383496

A comparative analysis of the results from 4 trials of beta-blocker therapy for heart failure: BEST, CIBIS-II, MERIT-HF, and COPERNICUS.

PubMed

Domanski, Michael J; Krause-Steinrauf, Heidi; Massie, Barry M; Deedwania, Prakash; Follmann, Dean; Kovar, David; Murray, David; Oren, Ron; Rosenberg, Yves; Young, James; Zile, Michael; Eichhorn, Eric

2003-10-01

Recent large randomized, controlled trials (BEST [Beta-blocker Evaluation of Survival Trial], CIBIS-II [Cardiac Insufficiency Bisoprolol Trial II], COPERNICUS [Carvedilol Prospective Randomized Cumulative Survival Study], and MERIT-HF [Metoprolol Randomized Intervention Trial in Congestive Heart Failure]) have addressed the usefulness of beta-blockade in the treatment of advanced heart failure. CIBIS-II, COPERNICUS, and MERIT-HF have shown that beta-blocker treatment with bisoprolol, carvedilol, and metoprolol XL, respectively, reduce mortality in advanced heart failure patients, whereas BEST found a statistically nonsignificant trend toward reduced mortality with bucindolol. We conducted a post hoc analysis to determine whether the response to beta-blockade in BEST could be related to differences in the clinical and demographic characteristics of the study populations. We generated a sample from BEST to resemble the patient cohorts studied in CIBIS-II and MERIT-HF to find out whether the response to beta-blocker therapy was similar to that reported in the other trials. These findings are further compared with COPERNICUS, which entered patients with more severe heart failure. To achieve conformity with the entry criteria for CIBIS-II and MERIT-HF, the BEST study population was adjusted to exclude patients with systolic blood pressure <100 mm Hg, heart rate <60 bpm, and age >80 years (exclusion criteria employed in those trials). The BEST comparison subgroup (BCG) was further modified to more closely reflect the racial demographics reported for patients enrolled in CIBIS-II and MERIT-HF. The association of beta-blocker therapy with overall survival and survival free of cardiac death, sudden cardiac death, and progressive pump failure in the BCG was assessed. In the BCG subgroup, bucindolol treatment was associated with significantly lower risk of death from all causes (hazard ratio (HR)=0.77 [95% CI=0.65, 0.92]), cardiovascular death (HR=0.71 [0.58, 0.86]), sudden death (HR=0.77 [0.59, 0.999]), and pump failure death (HR=0.64 [0.45, 0.91]). Although not excluding the possibility of differences resulting from chance alone or to different properties among beta-blockers, this study suggests the possibility that different heart failure population subgroups may have different responses to beta-blocker therapy.

Securing All intraVenous devices Effectively in hospitalised patients—the SAVE trial: study protocol for a multicentre randomised controlled trial

PubMed Central

Rickard, Claire M; Marsh, Nicole; Webster, Joan; Playford, E Geoffrey; McGrail, Matthew R; Larsen, Emily; Keogh, Samantha; McMillan, David; Whitty, Jennifer A; Choudhury, Md Abu; Dunster, Kimble R; Reynolds, Heather; Marshall, Andrea; Crilly, Julia; Young, Jeanine; Thom, Ogilvie; Gowardman, John; Corley, Amanda; Fraser, John F

2015-01-01

Introduction Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. Methods and analysis A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethics and dissemination Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Trial registration number Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. PMID:26399574

The association between market availability and adherence to antihypertensive medications: an observational study.

PubMed

Evans, Charity D; Eurich, Dean T; Lu, Xinya; Remillard, Alfred J; Shevchuk, Yvonne M; Blackburn, David

2013-02-01

High adherence to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reported in observational studies has frequently been attributed to improved tolerability. However, these agents are also relatively new to the market compared to other antihypertensive medications. We aimed to determine if an association exists between adherence and market availability of a specific antihypertensive agent. This retrospective cohort study used administrative data from Saskatchewan, Canada. Subjects were ≥40 years of age and received a new antihypertensive medication between 1994 and 2002. The primary outcome was the proportion of subjects achieving optimal adherence (≥80%) at 1 year, stratified by antihypertensive medication class and the year of availability. Adherence was measured using the cumulative mean gap ratio. A total of 36,214 subjects met the inclusion criteria. Optimal adherence was observed in 4987 of 8623 (57.8%) subjects receiving ACEIs and 1013 of 1600 (63.3%) subjects receiving ARBs, but adherence appeared inconsistent when examined within each antihypertensive class. A pattern of increasing mean adherence was observed according to availability in the ACEI subgroup (Spearman r = 0.82; P = 0.007) but not the ARB subgroup (Spearman r = 0.41; P = 0.49). However, the association between availability and optimal adherence converged when ARB and ACEI users were combined (Spearman r = 0.85, P < 0.001). Optimal adherence with ACEIs and ARBs compared to other antihypertensive agents may be associated with their relative availability. To what extent optimal adherence is also associated with improved tolerability, as currently believed, remains to be determined.

Association of perceived job insecurity with ischemic heart disease and antihypertensive medication in the Danish Work Environment Cohort Study 1990-2010.

PubMed

Latza, Ute; Rossnagel, Karin; Hannerz, Harald; Burr, Hermann; Jankowiak, Sylvia; Backé, Eva-Maria

2015-11-01

To determine the effect of job insecurity based on repeated measurements on ischemic heart disease (IHD) and on antihypertensive medication. The study population consists of 12,559 employees aged 18-59 years of the Danish Work Environment Cohort Study. With an open cohort design, data from up to four representative waves were linked to four registers. Poisson regression with time-dependent covariates was used to estimate the rate ratio (RR) with confidence interval (CI) of perceived job insecurity associated with first-time IHD hospitalization or mortality 1991-2010 (n = 561 cases) and incident dispensing of prescribed antihypertensive medications 1996-2010 (n = 2,402 cases). Participants with perceived job insecurity filled more antihypertensive prescriptions (age-, gender-, and calendar year-adjusted RR 1.23, 95 % CI 1.12-1.33) and had a borderline significant higher IHD incidence (RR 1.23, 95 % CI 0.98-1.55). In a subanalysis, the risk of antihypertensive medication dispensed was only significant among employees with worries about both unemployment and poor reemployment opportunities. After explorative stratifications by age, gender, and occupational status, perceived job insecurity was associated with more dispensing of antihypertensive medications to participants less than 50 years of age. In a country with high social security and active labor market policy, employees with the feeling of an insecure job have a modestly increased risk to fill an antihypertensive prescription. Further studies on health risks of job insecurity should consider improved exposure assessment, earlier outcomes such as medication in order to increase statistical power, and identification of vulnerable population groups.

Relation between chemical composition or antioxidant activity and antihypertensive activity for six essential oils.

PubMed

Yvon, Yan; Raoelison, Emmanuel Guy; Razafindrazaka, René; Randriantsoa, Adolphe; Romdhane, Mehrez; Chabir, Naziha; Mkaddem, Mounira Guedri; Bouajila, Jalloul

2012-08-01

Six essential oils (EOs), Juniperus phoenicea (leaves and berries), Thymus capitatus, Lauris nobilis, Melaleuca armillaris, and Eucalyptus gracilis, were screened for their antioxidant and antihypertensive activity as well as their chemical compositions. We identified and quantified 24 compounds (representing 99.8% of total oil) for J. phoenicea leaves, 14 compounds (representing 98.8% of total oil) for J. phoenicea berries, 11 compounds (representing 99.6% of total oil) for T. capitatus, 32 compounds (representing 98.9% of total oil) for L. nobilis, 32 compounds (representing 98.7% of total oil) for M. armillaris, and 26 compounds (representing 99.3% of total oil) for E. gracilis. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, the antioxidant activity was in the range of 0.59 to 2183.6 mg/L, whereas T. capitatus (1.24 ± 0.05 mg/L) gave the best activity in the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonate assay. Antihypertensive activity was evaluated by testing the vasorelaxing capacity of EOs on rat aorta precontracted by phenylephrine (10(-6) M). T. capitatus and L. nobilis were most active for an antihypertensive activity (29 ± 3 and 59 ± 2 mg/L, respectively). Correlations between chemical composition or antioxidant activity and/or antihypertensive activity were studied. Significant correlation has been found for antihypertensive activity and p-cymene (R(2) = 0.86), β-elemene (R(2) = 0.90), and β-myrcene (R(2) = 0.76). A good correlation has been found between antihypertensive activity and antioxidant activity by DPPH assay (R(2) = 0.98). Antioxidant activity can contribute to the prevention of the increase of the blood pressure. According to the literature, no study has been reported until now of correlation between antihypertensive activity and antioxidant activity. Natural EOs can find its interest and application in a medicinal area. © 2012 Institute of Food Technologists®

Physicochemical equivalence of generic antihypertensive medicines (EQUIMEDS): protocol for a quality of medicines assessment

PubMed Central

Redfern, Julie; Adedoyin, Rufus Adesoji; Ofori, Sandra; Anchala, Raghupathy; Ajay, Vamadevan S; De Andrade, Luciano; Zelaya, Jose; Kaur, Harparkash; Balabanova, Dina; Sani, Mahmoud U

2016-01-01

Background Prevention and optimal management of hypertension in the general population is paramount to the achievement of the World Heart Federation (WHF) goal of reducing premature cardiovascular disease (CVD) mortality by 25% by the year 2025 and widespread access to good quality antihypertensive medicines is a critical component for achieving the goal. Despite research and evidence relating to other medicines such as antimalarials and antibiotics, there is very little known about the quality of generic antihypertensive medicines in low-income and middle-income countries. The aim of this study was to determine the physicochemical equivalence (percentage of active pharmaceutical ingredient, API) of generic antihypertensive medicines available in the retail market of a developing country. Methods An observational design will be adopted, which includes literature search, landscape assessment, collection and analysis of medicine samples. To determine physicochemical equivalence, a multistage sampling process will be used, including (1) identification of the 2 most commonly prescribed classes of antihypertensive medicines prescribed in Nigeria; (2) identification of a random sample of 10 generics from within each of the 2 most commonly prescribed classes; (3) a geographical representative sampling process to identify a random sample of 24 retail outlets in Nigeria; (4) representative sample purchasing, processing to assess the quality of medicines, storage and transport; and (5) assessment of the physical and chemical equivalence of the collected samples compared to the API in the relevant class. In total, 20 samples from each of 24 pharmacies will be tested (total of 480 samples). Discussion Availability of and access to quality antihypertensive medicines globally is therefore a vital strategy needed to achieve the WHF 25×25 targets. However, there is currently a scarcity of knowledge about the quality of antihypertensive medicines available in developing countries. Such information is important for enforcing and for ensuring the quality of antihypertensive medicines. PMID:28588941

Clinical importance of detecting exaggerated blood pressure response to exercise on antihypertensive therapy.

PubMed

Mizuno, Reiko; Fujimoto, Shinichi; Saito, Yoshihiko; Yamazaki, Masaharu

2016-06-01

In patients with hypertension, regression of left ventricular hypertrophy (LVH) is associated with improved prognosis. Impact of exaggerated blood pressure response to exercise (Ex-BP) seen in patients with hypertension undergoing antihypertensive therapy on the regression of LVH has not been evaluated. This prospective study investigated the relationship between Ex-BP on antihypertensive therapy and the regression of LVH. We prospectively studied 124 never-treated patients with hypertension with LVH. After a pretreatment evaluation, antihypertensive treatment was started and exercise test was performed in all patients. Patients with Ex-BP were divided into the Ex-BP (+) group and those without were divided into the Ex-BP (-) group. Regression of LVH over the follow-up period was compared between the groups. The follow-up duration was approximately 12 months in both the groups. Mean values of blood pressure at rest during the follow-up period were similar between the groups. Reduction of LVH was seen in both the groups. The magnitude of reduction of LVH was significantly smaller in the Ex-BP (+) group compared with the Ex-BP (-) group. Regression of LVH was much frequently seen in the Ex-BP (+) group compared with the Ex-BP (-) group. Multiple regression analysis determined that on-treatment Ex-BP was an independent negative determinant of antihypertensive treatment-induced reduction of LVH. This study suggests that on-treatment Ex-BP is associated with depressed regression of LVH in patients with hypertension with antihypertensive treatment. If Ex-BP is detected despite receiving antihypertensive agents, improvement of Ex-BP may be necessary to achieve an effective reduction of LVH. Active search of Ex-BP is recommended in patients with hypertension with antihypertensive treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF).

PubMed

McMurray, John J V; Anand, Inder S; Diaz, Rafael; Maggioni, Aldo P; O'Connor, Christopher; Pfeffer, Marc A; Solomon, Scott D; Tendera, Michal; van Veldhuisen, Dirk J; Albizem, Moetaz; Cheng, Sunfa; Scarlata, Debra; Swedberg, Karl; Young, James B

2013-03-01

This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate < 60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106-117) g/L. The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.

Clinical Outcomes by Race in Hypertensive Patients with and without the Metabolic Syndrome in ALLHAT

PubMed Central

Wright, Jackson T.; Harris-Haywood, Sonja; Pressel, Sara; Barzilay, Joshua; Baimbridge, Charles; Bareis, Charles J.; Basile, Jan N.; Black, Henry R.; Dart, Richard; Gupta, Alok K.; Hamilton, Bruce P.; Einhorn, Paula T.; Haywood, L. Julian; Jafri, Syed Z.A.; Louis, Gail T.; Whelton, Paul K.; Scott, Cranford L.; Simmons, Debra L.; Stanford, Carol; Davis, Barry R.

2009-01-01

Background Antihypertensive drugs with favorable metabolic effects on glucose and lipid levels are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcomes by race in black and nonblack hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an α-blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Methods A post hoc subgroup analysis from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled hypertension treatment trial in 42 418 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30 kg/m2, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men (or less than 50 mg/dL in women). Results Significantly higher rates of heart failure were consistent across all treatment comparisons in those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval [CI], 1.18–1.90), 1.49 (95% CI, 1.17–1.90), and 1.88 (95% CI, 1.42–2.47) in black participants and 1.25 (95% CI, 1.06–1.47), 1.20 (95% CI, 1.01–1.41), and 1.82 (95% CI, 1.51–2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RR, 1.24 [95% CI, 1.09–1.40] and 1.10 [95% CI, 1.02–1.19], respectively) and doxazosin-chlorthalidone comparisons (RR, 1.37 [95% CI, 1.19–1.58] and 1.18 [95% CI, 1.08– 1.30], respectively), in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 [95% CI, 1.07–1.76] for the lisinopril-chlorthalidone comparison; RR, 1.49 [95% CI, 1.09–2.03] for the doxazosin-chlorthalidone comparison). Black patients with MetS also had higher rates of end-stage renal disease (RR, 1.70 1 [95% CI, 1.13– 2.55]) with lisinopril compared with chlorthalidone. Conclusions The ALLHAT findings fail to do not support the preference of for calcium channel blockers, α-blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the MetS, despite their more favorable metabolic profiles. This was particularly true for black participants. PMID:18227370

Clinical effectiveness of hymenoptera venom immunotherapy: a prospective observational multicenter study of the European academy of allergology and clinical immunology interest group on insect venom hypersensitivity.

PubMed

Ruëff, Franziska; Przybilla, Bernhard; Biló, Maria Beatrice; Müller, Ulrich; Scheipl, Fabian; Seitz, Michael J; Aberer, Werner; Bodzenta-Lukaszyk, Anna; Bonifazi, Floriano; Campi, Paolo; Darsow, Ulf; Haeberli, Gabrielle; Hawranek, Thomas; Küchenhoff, Helmut; Lang, Roland; Quercia, Oliviero; Reider, Norbert; Schmid-Grendelmeier, Peter; Severino, Maurizio; Sturm, Gunter Johannes; Treudler, Regina; Wüthrich, Brunello

2013-01-01

Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy.

Blood pressure control in resistant hypertension: new therapeutic options.

PubMed

Grassi, Guido; Quarti-Trevano, Fosca; Brambilla, Gianmaria; Seravalle, Gino

2010-11-01

Resistant hypertension, namely the hypertensive state characterized by the inability of multiple antihypertensive drug interventions to lower blood pressure to goal levels, represents a condition frequently detected in clinical practice. Its main features are represented by its heterogeneous etiology as well as its very high cardiovascular risk. This latter peculiarity has implemented the research for new approaches to the treatment of the disease. This article will focus on two of them, namely carotid baroreceptor electric stimulation and the renal denervation procedure. Clinical studies and large-scale clinical trials are presently ongoing with the aim of defining the long-term efficacy and safety profile of the two interventions.

Shared decision-making in antihypertensive therapy: a cluster randomised controlled trial

PubMed Central

2013-01-01

Background Hypertension is one of the key factors causing cardiovascular diseases. A substantial proportion of treated hypertensive patients do not reach recommended target blood pressure values. Shared decision making (SDM) is to enhance the active role of patients. As until now there exists little information on the effects of SDM training in antihypertensive therapy, we tested the effect of an SDM training programme for general practitioners (GPs). Our hypotheses are that this SDM training (1) enhances the participation of patients and (2) leads to an enhanced decrease in blood pressure (BP) values, compared to patients receiving usual care without prior SDM training for GPs. Methods The study was conducted as a cluster randomised controlled trial (cRCT) with GP practices in Southwest Germany. Each GP practice included patients with treated but uncontrolled hypertension and/or with relevant comorbidity. After baseline assessment (T0) GP practices were randomly allocated into an intervention and a control arm. GPs of the intervention group took part in the SDM training. GPs of the control group treated their patients as usual. The intervention was blinded to the patients. Primary endpoints on patient level were (1) change of patients’ perceived participation (SDM-Q-9) and (2) change of systolic BP (24h-mean). Secondary endpoints were changes of (1) diastolic BP (24h-mean), (2) patients’ knowledge about hypertension, (3) adherence (MARS-D), and (4) cardiovascular risk score (CVR). Results In total 1357 patients from 36 general practices were screened for blood pressure control by ambulatory blood pressure monitoring (ABPM). Thereof 1120 patients remained in the study because of uncontrolled (but treated) hypertension and/or a relevant comorbidity. At T0 the intervention group involved 17 GP practices with 552 patients and the control group 19 GP practices with 568 patients. The effectiveness analysis could not demonstrate a significant or relevant effect of the SDM training on any of the endpoints. Conclusion The study hypothesis that the SDM training enhanced patients’ perceived participation and lowered their BP could not be confirmed. Further research is needed to examine the impact of patient participation on the treatment of hypertension in primary care. Trial registration German Clinical Trials Register (DRKS): DRKS00000125 PMID:24024587

Efficacy and safety of electroacupuncture in acute decompensated heart failure: a study protocol for a randomized, patient- and assessor-blinded, sham controlled trial.

PubMed

Leem, Jungtae; Lee, Seung Min Kathy; Park, Jun Hyeong; Lee, Suji; Chung, Hyemoon; Lee, Jung Myung; Kim, Weon; Lee, Sanghoon; Woo, Jong Shin

2017-07-11

The purpose of this trial is to evaluate the effectiveness and safety of electroacupuncture in the treatment of acute decompensated heart failure compared with sham electroacupuncture. This protocol is for a randomized, sham controlled, patient- and assessor-blinded, parallel group, single center clinical trial that can overcome the limitations of previous trials examining acupuncture and heart failure. Forty-four acute decompensated heart failure patients admitted to the cardiology ward will be randomly assigned into the electroacupuncture treatment group (n = 22) or the sham electroacupuncture control group (n = 22). Participants will receive electroacupuncture treatment for 5 days of their hospital stay. The primary outcome of this study is the difference in total diuretic dose between the two groups during hospitalization. On the day of discharge, follow-up heart rate variability, routine blood tests, cardiac biomarkers, high-sensitivity C-reactive protein (hs-CRP) level, and N-terminal pro b-type natriuretic peptide (NT-pro BNP) level will be assessed. Four weeks after discharge, hs-CRP, NT-pro BNP, heart failure symptoms, quality of life, and a pattern identification questionnaire will be used for follow-up analysis. Six months after discharge, major cardiac adverse events and cardiac function measured by echocardiography will be assessed. Adverse events will be recorded during every visit. The result of this clinical trial will offer evidence of the effectiveness and safety of electroacupuncture for acute decompensated heart failure. Clinical Research Information Service: KCT0002249 .

The utility of levosimendan in the treatment of heart failure.

PubMed

Lehtonen, Lasse; Põder, Pentti

2007-01-01

Calcium sensitizers are a new group of inotropic drugs. Levosimendan is the only calcium sensitizer in clinical use in Europe. Its mechanism of action includes both calcium sensitization of contractile proteins and the opening of adenosine triphosphate (ATP)-dependent potassium channels as mechanism of vasodilation. The combination of K-channel opening with positive inotropy offers potential benefits in comparison to currently available intravenous inotropes, since K-channel opening protects myocardium during ischemia. Due to the calcium-dependent binding of levosimendan to troponin C, the drug increases contractility without negative lusitropic effects. In patients with heart failure levosimendan dose-dependently increases cardiac output and reduces pulmonary capillary wedge pressure. Since levosimendan has an active metabolite OR-1896 with a half-life of some 80 hours, the duration of the hemodynamic effects significantly exceeds the 1-hour half-life of the parent compound. The hemodynamic effects of the levosimendan support its use in acute and postoperative heart failure. Several moderate-size trials (LIDO, RUSSLAN, CASINO) have previously suggested that the drug might even improve the prognosis of patients with decompensated heart failure. These trials were carried out in patients with high filling pressures. Recently two larger trials (SURVIVE and REVIVE) in patients who were hospitalized because of worsening heart failure have been finalized. These trials did not require filling pressures to be measured. The two trials showed that levosimendan improves the symptoms of heart failure, but does not improve survival. The results raise the question whether a 24-hour levosimendan infusion can be used without invasive hemodynamic monitoring.

The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications.

PubMed

Viecelli, Andrea K; Pascoe, Elaine; Polkinghorne, Kevan R; Hawley, Carmel; Paul-Brent, Peta-Anne; Badve, Sunil V; Cass, Alan; Heritier, Stephane; Kerr, Peter G; Mori, Trevor A; Robertson, Amanda; Seong, Hooi L; Irish, Ashley B

2015-06-27

The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design. The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure. This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enroll a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study. Australia & New Zealand Clinical Trial Register (ACTRN12607000569404).

Influence of Clinical Trial Site Enrollment on Patient Characteristics, Protocol Completion, and End Points: Insights From the ASCEND-HF Trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).

PubMed

Greene, Stephen J; Hernandez, Adrian F; Sun, Jie-Lena; Metra, Marco; Butler, Javed; Ambrosy, Andrew P; Ezekowitz, Justin A; Starling, Randall C; Teerlink, John R; Schulte, Phillip J; Voors, Adriaan A; Armstrong, Paul W; O'Connor, Christopher M; Mentz, Robert J

2016-09-01

Most international acute heart failure trials have failed to show benefit with respect to key end points. The impact of site enrollment and protocol execution on trial performance is unclear. We assessed the impact of varying site enrollment volume among all 7141 acute heart failure patients from the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure). Overall, 398 sites enrolled ≥1 patient, and median enrollment was 12 patients (interquartile range, 5-23). Patients from high enrolling sites (>60 patients/site) tended to have lower ejection fraction, worse New York Heart Association functional class, and lower utilization of guideline-directed medical therapy but fewer comorbidities and lower B-type natriuretic peptide level. Every 10 patient increase (up to 100 patients) in site enrollment correlated with lower likelihood of protocol noncompletion (odds ratio, 0.93; 95% confidence interval [CI], 0.89-0.98). After adjustment, increasing site enrollment predicted higher risk of persistent dyspnea at 6 hours (per 10 patient increase: odds ratio 1.02; 95% CI, 1.01-1.03) but not at 24 hours (odds ratio, 0.99; 95% CI, 0.98-1.00). Higher site enrollment was independently associated with lower risk of 30-day death or rehospitalization (per 10 patient increase: odds ratio, 0.98, 95% CI, 0.96-0.99) but not 180-day mortality (hazard ratio, 0.99; 95% CI, 0.98-1.01). The influence of increasing site enrollment on clinical end points varied across geographic regions with strongest associations in Latin America and Asia-Pacific (all interaction P<0.01). In this large, acute heart failure trial, site enrollment correlated with protocol completion and was independently associated with trial end points. Individual and regional site performance present challenges to be considered in design of future acute heart failure trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852. © 2016 American Heart Association, Inc.

Failure and Success of Percutaneous Angioplasty in a Hypertensive Child with Bilateral Renal Artery Stenosis

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

Giavroglou, Constantinos; Tsifountoudis, Ioannis, E-mail: jtsif@mycosmos.g; Boutzetis, Theodoros

2009-01-15

We describe the clinical course of a 5-year-old girl with severe arterial hypertension that was uncontrollable with antihypertensive medication. Renal angiography revealed bilateral renal artery stenoses. Because percutaneous transluminal renal angioplasty (PTRA) failed to dilate the stenotic lesions, a renal artery bypass grafting in both renal arteries was performed. The patient remained normotensive for 7 months, and after that the arterial pressure increased again. Digital subtraction angiography demonstrated stenosis at the peripheral and central anastomosis of the vein graft that was used for revascularization of the left kidney. PTRA was decided on and successful patency was achieved. The patient hasmore » now been normotensive for a period of 5 years.« less

Vitamin D and Heart Failure.

PubMed

Marshall Brinkley, D; Ali, Omair M; Zalawadiya, Sandip K; Wang, Thomas J

2017-10-01

Vitamin D is principally known for its role in calcium homeostasis, but preclinical studies implicate multiple pathways through which vitamin D may affect cardiovascular function and influence risk for heart failure. Many adults with cardiovascular disease have low vitamin D status, making it a potential therapeutic target. We review the rationale and potential role of vitamin D supplementation in the prevention and treatment of chronic heart failure. Substantial observational evidence has associated low vitamin D status with the risk of heart failure, ventricular remodeling, and clinical outcomes in heart failure, including mortality. However, trials assessing the influence of vitamin D supplementation on surrogate markers and clinical outcomes in heart failure have generally been small and inconclusive. There are insufficient data to recommend routine assessment or supplementation of vitamin D for the prevention or treatment of chronic heart failure. Prospective trials powered for clinical outcomes are warranted.

Safety, Tolerability, and Antihypertensive Effect of SER100, an Opiate Receptor-Like 1 (ORL-1) Partial Agonist, in Patients With Isolated Systolic Hypertension.

PubMed

Kantola, Ilkka; Scheinin, Mika; Gulbrandsen, Trygve; Meland, Nils; Smerud, Knut T

2017-11-01

The purpose of the present trial was to evaluate safety, tolerability, and effect on systolic blood pressure (SBP) of SER100 in a small group of patients with isolated systolic hypertension (ISH) in treatment with at least 1 antihypertensive drug. Eligible patients were randomized to either SER100 (10 mg) or placebo in a crossover design, and 2 doses were given subcutaneously (SC), 8 hours apart, on 2 consecutive days. On all treatment days patients were monitored with an ambulatory blood pressure measurement device for 12 daytime hours. Seventeen patients completed treatment. There were no serious or severe adverse events. Relative to placebo SER100 induced an average reduction of SBP during the 2 treatment days of 7.0 mm Hg (P = 0.0032), whereas the average reduction of diastolic blood pressure (DBP) over the same period was 3.8 mm Hg (P = 0.0011). For patients with ISH, this short-term cross-over study of SC SER100 demonstrated an acceptable safety profile and consistent, significant lowering of SBP and DBP. As initial clinical proof of concept for a new class of drugs, a nociceptin agonist peptide, the results were encouraging and warrant further research. © 2016, The American College of Clinical Pharmacology.

Clinical efficacy and safety of olmesartan/hydrochlorothiazide combination therapy in patients with essential hypertension

PubMed Central

Ruilope, Luis M

2008-01-01

Hypertension is a major risk factor for cardiovascular disease that contributes to the premature death of millions of people each year, and identification and treatment of hypertension continues to be a challenge. Guidelines recommend that many patients will require two or more antihypertensive agents from different classes. Combining an angiotensin II receptor blocker (ARB) with hydrochlorothiazide (HCTZ) has been shown in clinical studies to increase the antihypertensive efficacy of both agents compared with either agent alone. This review covers several clinical trials and aims to examine several aspects of the efficacy of the combination of olmesartan and HCTZ, including dose-responsiveness, long-term efficacy, goal rate achievement, and efficacy in patients with moderate to severe hypertension. The results presented here demonstrate that olmesartan is effective when added to HCTZ monotherapy or when HCTZ is added to olmesartan monotherapy, both over the short and long term. Moderate to severe hypertension responds well to olmesartan/HCTZ combination therapy, and the great majority of patients are able to achieve recommended blood pressure targets. Thus olmesartan/HCTZ is a well-tolerated option for patients who fail to respond to monotherapy and as initial therapy in those who require large reductions in diastolic blood pressure or systolic blood pressure to achieve goal blood pressure. PMID:19337537

Aerobic exercise reduces blood pressure in resistant hypertension.

PubMed

Dimeo, Fernando; Pagonas, Nikolaos; Seibert, Felix; Arndt, Robert; Zidek, Walter; Westhoff, Timm H

2012-09-01

Regular physical exercise is broadly recommended by current European and American hypertension guidelines. It remains elusive, however, whether exercise leads to a reduction of blood pressure in resistant hypertension as well. The present randomized controlled trial examines the cardiovascular effects of aerobic exercise on resistant hypertension. Resistant hypertension was defined as a blood pressure ≥140/90 mm Hg in spite of 3 antihypertensive agents or a blood pressure controlled by ≥4 antihypertensive agents. Fifty subjects with resistant hypertension were randomly assigned to participate or not to participate in an 8- to 12-week treadmill exercise program (target lactate, 2.0±0.5 mmol/L). Blood pressure was assessed by 24-hour monitoring. Arterial compliance and cardiac index were measured by pulse wave analysis. The training program was well tolerated by all of the patients. Exercise significantly decreased systolic and diastolic daytime ambulatory blood pressure by 6±12 and 3±7 mm Hg, respectively (P=0.03 each). Regular exercise reduced blood pressure on exertion and increased physical performance as assessed by maximal oxygen uptake and lactate curves. Arterial compliance and cardiac index remained unchanged. Physical exercise is able to decrease blood pressure even in subjects with low responsiveness to medical treatment. It should be included in the therapeutic approach to resistant hypertension.

Reduction of Blood Pressure Following After Renal Artery Adventitia Stripping During Total Nephroureterectomy: Potential Effect of Renal Sympathetic Denervation

PubMed Central

Okamura, Keisuke; Satou, Shunsuke; Setojima, Keita; Shono, Shinjiro; Miyajima, Shigero; Ishii, Tatsu; Shirai, Kazuyuki; Urata, Hidenori

2018-01-01

Case series Patients: Male, 85 • Male, 89 Final Diagnosis: Essential hypertension Symptoms: High blood pressure Medication: Anti-hypertensive agents Clinical Procedure: Operation Specialty: Cardiology and Hypertension Objective: Unusual or unexpected effect of treatment Background: Catheter-based renal sympathetic denervation has been reported to be effective for treatment resistance hypertension in Australia and Europe. However, in the blinded SYMPLICITY HTN-3 trial, renal denervation did not achieve a significant decrease in blood pressure (BP) in comparison to sham controls. There have been various discussions on the factors that influenced this result. Case Reports: Two men on antihypertensive therapy underwent unilateral radical nephroureterectomy for cancer of the renal pelvis. When the renal artery adventitia was stripped and cauterized just before renal artery ligation, the measured BP of the 2 men increased after stripping adventitia and decreased gradually after cauterization of the renal artery. This was presumably due to removal of renal artery sympathetic nerves, similar to the mechanism of catheter-based renal sympathetic denervation, although anesthesia, fluid infusion, and/or mesenteric traction may have had an influence. Conclusions: A similar strategy involving thoracolumbar sympathectomy was reported about 50 years ago. The clinically significant blood pressure reduction in these patients suggests renal denervation is effective. PMID:29765015

A randomized trial of heart failure disease management in skilled nursing facilities (SNF Connect): Lessons learned.

PubMed

Daddato, Andrea; Wald, Heidi L; Horney, Carolyn; Fairclough, Diane L; Leister, Erin C; Coors, Marilyn; Capell, Warren H; Boxer, Rebecca S

2017-06-01

Conducting clinical trials in skilled nursing facilities is particularly challenging. This manuscript describes facility and patient recruitment challenges and solutions for clinical research in skilled nursing facilities. Lessons learned from the SNF Connect Trial, a randomized trial of a heart failure disease management versus usual care for patients with heart failure receiving post-acute care in skilled nursing facilities, are discussed. Description of the trial design and barriers to facility and patient recruitment along with regulatory issues are presented. The recruitment of Denver-metro skilled nursing facilities was facilitated by key stakeholders of the skilled nursing facilities community. However, there were still a number of barriers to facility recruitment including leadership turnover, varying policies regarding research, fear of litigation and of an increased workload. Engagement of facilities was facilitated by their strong interest in reducing hospital readmissions, marketing potential to hospitals, and heart failure management education for their staff. Recruitment of patients proved difficult and there were few facilitators. Identified patient recruitment challenges included patients being unaware of their heart failure diagnosis, patients overwhelmed with their illness and care, and frequently there was no available proxy for cognitively impaired patients. Flexibility in changing the recruitment approach and targeting skilled nursing facilities with higher rates of admissions helped to overcome some barriers. Recruitment of skilled nursing facilities and patients in skilled nursing facilities for clinical trials is challenging. Strategies to attract both facilities and patients are warranted. These include aligning study goals with facility incentives and flexible recruitment protocols to work with patients in "transition crisis."

Is the PARADIGM-HF cohort representative of the real-world heart failure patient population?

PubMed

Rodrigues, Gustavo; Tralhão, António; Aguiar, Carlos; Freitas, Pedro; Ventosa, António; Mendes, Miguel

2018-06-01

A new drug with prognostic impact on heart failure, sacubitril/valsartan, has been introduced in current guidelines. However, randomized trial results can be compromised by lack of representativeness. We aimed to assess the representativeness of the PARADIGM-HF trial in a real-world population of patients with heart failure. We reviewed the records of 196 outpatients followed in a heart failure clinic between January 2013 and December 2014. After exclusion of 44 patients with preserved ejection fraction, the inclusion and exclusion criteria of the trial were applied. Of the 152 patients with systolic heart failure, 106 lacked one or more inclusion criteria and 45 had at least one exclusion criterion. Considering only patients with ejection fraction ≤35% (HFrEF) (n=88), 43 patients lacked at least one inclusion criterion and 25 patients had at least one exclusion criterion. Combining the inclusion and exclusion criteria, 24.3% of patients with systolic HF (ejection fraction ≤50%) and 42% of patients with HFrEF would be eligible for the PARADIGM-HF trial. One in four patients with systolic HF followed in a heart failure outpatient clinic would fulfill the reference study criteria for treatment with the new drug, sacubitril/valsartan. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Foundations of Pharmacotherapy for Heart Failure With Reduced Ejection Fraction: Evidence Meets Practice, Part I.

PubMed

Paul, Sara; Page, Robert L

2016-01-01

Pharmacologic treatment for systolic heart failure, otherwise known as heart failure with reduced ejection fraction, has been established through clinical trials and is formulated into guidelines to standardize the diagnosis and treatment. The premise of pharmacologic therapy in heart failure with reduced ejection fraction is aimed primarily at interrupting the neurohormonal cascade that is responsible for altering left ventricular shape and function. This is the first in a series of articles to describe the pharmacologic agents in the guidelines that impact the morbidity and mortality associated with heart failure. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and vasodilators will be presented in the context of the mechanism of action in heart failure, investigational trials that showed beneficial effects, and the practical application for clinical use.

The contribution of attentional lapses to individual differences in visual working memory capacity.

PubMed

Adam, Kirsten C S; Mance, Irida; Fukuda, Keisuke; Vogel, Edward K

2015-08-01

Attentional control and working memory capacity are important cognitive abilities that substantially vary between individuals. Although much is known about how attentional control and working memory capacity relate to each other and to constructs like fluid intelligence, little is known about how trial-by-trial fluctuations in attentional engagement impact trial-by-trial working memory performance. Here, we employ a novel whole-report memory task that allowed us to distinguish between varying levels of attentional engagement in humans performing a working memory task. By characterizing low-performance trials, we can distinguish between models in which working memory performance failures are caused by either (1) complete lapses of attention or (2) variations in attentional control. We found that performance failures increase with set-size and strongly predict working memory capacity. Performance variability was best modeled by an attentional control model of attention, not a lapse model. We examined neural signatures of performance failures by measuring EEG activity while participants performed the whole-report task. The number of items correctly recalled in the memory task was predicted by frontal theta power, with decreased frontal theta power associated with poor performance on the task. In addition, we found that poor performance was not explained by failures of sensory encoding; the P1/N1 response and ocular artifact rates were equivalent for high- and low-performance trials. In all, we propose that attentional lapses alone cannot explain individual differences in working memory performance. Instead, we find that graded fluctuations in attentional control better explain the trial-by-trial differences in working memory that we observe.

The Contribution of Attentional Lapses to Individual Differences in Visual Working Memory Capacity

PubMed Central

Adam, Kirsten C. S.; Mance, Irida; Fukuda, Keisuke; Vogel, Edward K.

2015-01-01

Attentional control and working memory capacity are important cognitive abilities that substantially vary between individuals. Although much is known about how attentional control and working memory capacity relate to each other and to constructs like fluid intelligence, little is known about how trial-by-trial fluctuations in attentional engagement impact trial-by-trial working memory performance. Here, we employ a novel whole-report memory task that allowed us to distinguish between varying levels of attentional engagement in humans performing a working memory task. By characterizing low-performance trials, we can distinguish between models in which working memory performance failures are caused by either (1) complete lapses of attention or (2) variations in attentional control. We found that performance failures increase with set-size and strongly predict working memory capacity. Performance variability was best modeled by an attentional control model of attention, not a lapse model. We examined neural signatures of performance failures by measuring EEG activity while participants performed the whole-report task. The number of items correctly recalled in the memory task was predicted by frontal theta power, with decreased frontal theta power associated with poor performance on the task. In addition, we found that poor performance was not explained by failures of sensory encoding; the P1/N1 response and ocular artifact rates were equivalent for high- and low-performance trials. In all, we propose that attentional lapses alone cannot explain individual differences in working memory performance. Instead, we find that graded fluctuations in attentional control better explain the trial-by-trial differences in working memory that we observe. PMID:25811710

[Evaluation of antihypertensive therapy by ambulatory blood pressure monitoring and establishment of the level of antihypertensive goal on the circadian rhythm of blood pressure].

PubMed

Fujioka, T; Tamaki, S; Fudo, T; Nakae, I; Sugawara, A; Kambara, H

1990-01-01

We have developed a new method for the evaluation of antihypertensive therapy on the circadian rhythm of blood pressure and attempted to determine the indications for antihypertensive therapy and the level of antihypertensive goal. Blood pressures were measured for 24 hours by the use of ambulatory blood pressure monitoring using 630 (ABPM-630) in 50 normotensives, 50 untreated hypertensives and 50 hypertensives undertreatment with various antihypertensive drugs (110 males and 40 females, with a mean age of 53.4 +/- 13.3 yrs). Blood pressure profiles were prepared for determination of the hyperbaric and hypobaric indexes. According to the WHO's definitions for blood pressure, the hyperbaric index was defined as the area above 140 mmHg in systolic blood pressure or 90 mmHg in diastolic blood pressure, and the hypobaric index, as the area below 100 mmHg or 60 mmHg, respectively. The criteria of the hypobaric index was obtained from the mean basal blood pressure (the lowest blood pressure during sleep) of the 50 normotensives. The mean hyperbaric index of the 50 normotensives was 20.4 +/- 40.2/5.5 +/- 15.3 (systole/diastole) mmHg.hour/day and the mean hypobaric index, 12.2 +/- 22.5/9.0 +/- 24.0 mmHg.hour/day. The 50 untreated hypertensives showed a mean hyperbaric index of 281.8 +/- 197.0/156.0 +/- 126.1 mmHg.hour/day and a mean hypobaric index of 0.1 +/- 0.6/0.3 +/- 1.5 mmHg.hour/day. Comparison of the indexes before and after treatment with various antihypertensives showed that a decrease in the hyperbaric index without an increase in the hypobaric index was the most optimal reduction of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review

PubMed Central

2013-01-01

Background Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. Methods Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. Results We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. Conclusion Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs. PMID:23721258

Blood Pressure in Children with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children Study

PubMed Central

Flynn, Joseph T; Mitsnefes, Mark; Pierce, Christopher; Cole, Steven R; Parekh, Rulan S; Furth, Susan L; Warady, Bradley A

2011-01-01

To characterize the distribution of blood pressure (BP), prevalence and risk factors for hypertension in pediatric chronic kidney disease (CKD), we conducted a cross-sectional analysis of baseline BP's in 432 children (mean age 11y; 60% male; mean glomerular filtration rate [GFR] 44 ml/min/1.73m2) enrolled in the Chronic Kidney Disease in Children cohort study. BP's were obtained using an aneroid sphygmomanometer. GFR was measured by iohexol disappearance. Elevated BP was defined as BP≥90th percentile for age, gender and height. Hypertension was defined as BP≥95th percentile or as self-reported hypertension plus current treatment with antihypertensive medications. For systolic BP, 14% were hypertensive and 11% were pre-hypertensive (BP 90-95th percentile); 68% of subjects with elevated SBP were taking antihypertensive medications. For diastolic BP, 14% were hypertensive, and 9% were pre-hypertensive; 53% of subjects with elevated DBP were taking antihypertensive medications. 54% of subjects had either systolic or diastolic BP≥95th percentile or a history of hypertension plus current antihypertensive use. Characteristics associated with elevated BP included black race, shorter duration of CKD, absence of antihypertensive medication use, and elevated serum potassium. Among subjects receiving antihypertensive treatment, uncontrolled BP was associated with male sex, shorter CKD duration and absence of ACE inhibitor or ARB use. 37% of children with CKD had either elevated systolic or diastolic BP, and 39% of these were not receiving antihypertensives, indicating that hypertension in pediatric CKD may be frequently under- or even un-treated. Treatment with ACE inhibitors or ARB's may improve BP control in these patients. PMID:18725579

Long-term Effects of Antihypertensive Drug Use and New-onset Osteoporotic Fracture in Elderly Patients: A Population-based Longitudinal Cohort Study.

PubMed

Chen, Hung-Yi; Ma, Kai-Yan; Hsieh, Pei-Ling; Liou, Yi-Sheng; Jong, Gwo-Ping

2016-12-20

Antihypertensive drugs have been linked to new-onset osteoporotic fracture (NOF), and different classes of antihypertensive drugs may alter the risk for the development of NOF; however, the classic effect of different antihypertensive drugs on the development of NOF in the elderly has not been well studied during long-term follow-up. In this study, we investigated the association between different classic antihypertensives and the development of NOF in the elderly. This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance in Central Taiwan, China including case patients with NOF aged 65-80 years from January 2002 to December 2012 and non-NOF controls. Prescriptions for antihypertensives before the index date were retrieved from a prescription database. We estimated the hazard ratios (HR s) of NOF associated with antihypertensive use. Non-NOF controls served as the reference group. A total of 128 patients with NOF were identified from among 1144 patients with hypertension during the study period. The risk of NOF after adjusting age, sex, comorbidities, and concurrent medications was higher among the users of angiotensin-converting enzyme (ACE) inhibitors (HR, 1.64; 95% confidence interval [CI], 1.01-2.66) than among nonusers. Patients who took calcium channel blockers (CCBs) (HR, 0.70; 95% CI, 0.49-0.99) were at a lower risk of developing NOF than nonusers. Loop diuretics, thiazide diuretics, angiotensin receptor blocker, beta-blocker, and alpha-blocker were not associated with the risk of NOF. Elderly with hypertension who take CCBs are at a lower risk of NOF and that the use of ACE inhibitors was associated with a significantly increased risk of developing NOF during the 11-year follow-up.

Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial

PubMed Central

Kantor, Rami; Smeaton, Laura; Vardhanabhuti, Saran; Hudelson, Sarah E.; Wallis, Carol L.; Tripathy, Srikanth; Morgado, Mariza G.; Saravanan, Shanmugham; Balakrishnan, Pachamuthu; Reitsma, Marissa; Hart, Stephen; Mellors, John W.; Halvas, Elias; Grinsztejn, Beatriz; Hosseinipour, Mina C.; Kumwenda, Johnstone; La Rosa, Alberto; Lalloo, Umesh G.; Lama, Javier R.; Rassool, Mohammed; Santos, Breno R.; Supparatpinyo, Khuanchai; Hakim, James; Flanigan, Timothy; Kumarasamy, Nagalingeswaran; Campbell, Thomas B.; Eshleman, Susan H.

2015-01-01

Background. Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Methods. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance–failure association. Results. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex–treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04–2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22–.98). Conclusions. In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. Clinical Trials Registration. NCT00084136. PMID:25681380

Enhanced and Extended Anti-Hypertensive Effect of VP5 Nanoparticles

PubMed Central

Yu, Ting; Zhao, Shengnan; Li, Ziqiang; Wang, Yi; Xu, Bei; Fang, Dailong; Wang, Fazhan; Zhang, Zhi; He, Lili; Song, Xiangrong; Yang, Jian

2016-01-01

Hypertension has become a significant global public health concern and is also one of the most common risk factors of cardiovascular disease. Recent studies have shown the promising result of peptides inhibiting angiotensin converting enzyme (ACE) in lowering the blood pressure in both animal models and humans. However, the oral bioavailability and continuous antihypertensive effectiveness require further optimization. Novel nanoparticle-based drug delivery systems are helpful to overcome these barriers. Therefore, a poly-(lactic-co-glycolic) acid nanoparticle (PLGANPs) oral delivery system, of the antihypertensive small peptides Val-Leu-Pro-Val-Pro (VLPVP, VP5) model, was developed in this study and its antihypertensive effect was investigated in spontaneously hypertensive rats (SHRs) for the first time. The obtained VP5 nanoparticles (VP5-NPs) showed a small particle size of 223.7 ± 2.3 nm and high entrapment efficiency (EE%) of 87.37% ± 0.92%. Transmission electronic microscopy (TEM) analysis showed that the nanoparticles were spherical and homogeneous. The optimal preparation of VP5-NPs exhibited sustained release of VP5 in vitro and a 96 h long-term antihypertensive effect with enhanced efficacy in vivo. This study illustrated that PLGANPs might be an optimal formulation for oral delivery of antihypertensive small peptides and VP5-NPs might be worthy of further development and use as a potential therapeutic strategy for hypertension in the future. PMID:27898022

Impact of yoga on blood pressure and quality of life in patients with hypertension – a controlled trial in primary care, matched for systolic blood pressure

PubMed Central

2013-01-01

Background Medical treatment of hypertension is not always sufficient to achieve blood pressure control. Despite this, previous studies on supplementary therapies, such as yoga, are relatively few. We investigated the effects of two yoga interventions on blood pressure and quality of life in patients in primary health care diagnosed with hypertension. Methods Adult patients (age 20–80 years) with diagnosed hypertension were identified by an electronic chart search at a primary health care center in southern Sweden. In total, 83 subjects with blood pressure values of 120–179/≤109 mmHg at baseline were enrolled. At baseline, the patients underwent standardized blood pressure measurement at the health care center and they completed a questionnaire on self-rated quality of life (WHOQOL-BREF). There were three groups: 1) yoga class with yoga instructor (n = 28); 2) yoga at home (n = 28); and 3) a control group (n = 27). The participants were matched at the group level for systolic blood pressure. After 12 weeks of intervention, the assessments were performed again. At baseline a majority of the patients (92%) were on antihypertensive medication, and the patients were requested not to change their medication during the study. Results The yoga class group showed no improvement in blood pressure or self-rated quality of life, while in the yoga at home group there was a decline in diastolic blood pressure of 4.4 mmHg (p < 0.05) compared to the control group. Moreover, the yoga at home group showed significant improvement in self-rated quality of life compared to the control group (p < 0.05). Conclusions A short yoga program for the patient to practice at home seems to have an antihypertensive effect, as well as a positive effect on self-rated quality of life compared to controls. This implies that simple yoga exercises may be useful as a supplementary blood pressure therapy in addition to medical treatment when prescribed by primary care physicians. Trial registration ClinicalTrials.gov (NCT01302535) PMID:24314119

Effects of nitrates on mortality in acute myocardial infarction and in heart failure

PubMed Central

Held, P.

1992-01-01

1 Seven randomized controlled trials of intravenous nitroglycerin in a total of about 850 patients have been reported. Overall, there were 51 deaths (12.5%) in the nitroglycerin group and 87 (20%) in the control group. This indicates a 48% reduction in the odds of death (P < 0.001, 95% confidence limits (25% to 64%)). 2 There are five randomized trials of oral nitrates after acute myocardial infarction. In these trials, 11.8% of the patients in the nitrate group compared with 13.3% in the control group died. This indicates a nonsignificant 12% reduction in the odds of death but the 95% confidence interval overlaps widely with the i.v. trials. If all trials of i.v. or oral nitrates are considered the reduction in the odds of death is 32% (P < 0.01). 3 Nitrates have a beneficial effect on haemodynamics in heart failure but the data on mortality effects are sparse. In combination with hydralazine, however, long-term mortality was reduced in the V-HEFT trial of chronic heart failure. PMID:1633075

Minoxidil for Treatment of Resistant Hypertension in Chronic Kidney Disease--A Retrospective Cohort Analysis.

PubMed

Mundt, Heiko M; Matenaer, Matthias; Lammert, Alexander; Göttmann, Uwe; Krämer, Bernhard K; Birck, Rainer; Benck, Urs

2016-11-01

Resistant hypertension is still a challenge and reserve antihypertensive agents are often necessary to achieve blood pressure control. One reserve antihypertensive is minoxidil, a direct vasodilator that is known for its strong blood pressure-lowering effect, but contemporary studies are sparse. The authors retrospectively analyzed 54 inpatients with uncontrolled hypertension despite the combined use of current antihypertensive agents. To investigate the effect of minoxidil when added to other antihypertensive agents, blood pressure was evaluated at the time minoxidil treatment was initiated and at discharge. Minoxidil treatment was associated with a significant reduction in blood pressure from 162.4±15.1/83.2±12.7 mm Hg to 135.8±12.2/72.8±6.9 mm Hg (P<.0001). This effect was sustained across all analyzed subgroups. Although the well-known adverse events of minoxidil limit its widespread use, these data show that minoxidil as a reserve antihypertensive agent still has a niche indication in the particular subgroup of patients with treatment-resistant or uncontrolled hypertension. ©2016 Wiley Periodicals, Inc.

How Do Antihypertensive Drugs Work? Insights from Studies of the Renal Regulation of Arterial Blood Pressure

PubMed Central

Digne-Malcolm, Holly; Frise, Matthew C.; Dorrington, Keith L.

2016-01-01

Though antihypertensive drugs have been in use for many decades, the mechanisms by which they act chronically to reduce blood pressure remain unclear. Over long periods, mean arterial blood pressure must match the perfusion pressure necessary for the kidney to achieve its role in eliminating the daily intake of salt and water. It follows that the kidney is the most likely target for the action of most effective antihypertensive agents used chronically in clinical practice today. Here we review the long-term renal actions of antihypertensive agents in human studies and find three different mechanisms of action for the drugs investigated. (i) Selective vasodilatation of the renal afferent arteriole (prazosin, indoramin, clonidine, moxonidine, α-methyldopa, some Ca++-channel blockers, angiotensin-receptor blockers, atenolol, metoprolol, bisoprolol, labetolol, hydrochlorothiazide, and furosemide). (ii) Inhibition of tubular solute reabsorption (propranolol, nadolol, oxprenolol, and indapamide). (iii) A combination of these first two mechanisms (amlodipine, nifedipine and ACE-inhibitors). These findings provide insights into the actions of antihypertensive drugs, and challenge misconceptions about the mechanisms underlying the therapeutic efficacy of many of the agents. PMID:27524972

Clinical trials update from the Heart Failure Society of America Meeting 2009: FAST, IMPROVE-HF, COACH galectin-3 substudy, HF-ACTION nuclear substudy, DAD-HF, and MARVEL-1.

PubMed

Lainscak, Mitja; Coletta, Alison P; Sherwi, Nasser; Cleland, John G F

2010-02-01

This article presents findings and a commentary on late-breaking trials presented during the meeting of the Heart Failure Society of America in September 2009. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The FAST trial showed somewhat better performance of intrathoracic impedance for prediction of deterioration in patients with heart failure (HF) when compared with daily weighing. The IMPROVE-HF study reported the benefits of education on the management of patients with systolic HF. Galectin-3 appeared a useful method for improving risk stratification of patients with chronic HF in a substudy of the COACH trial. A nuclear substudy of the HF-ACTION trial failed to demonstrate that resting myocardial perfusion imaging, a measure of myocardial scar and viability, was clinically useful. A small randomized controlled trial (DAD-HF) suggested that the use of low-dose dopamine in patients with acutely decompensated HF was associated with less deterioration in renal function and less hypokalaemia. The MARVEL-1 trial raises further concerns about the safety of myoblast transplantation in ischaemic HF.

Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials.

PubMed

Walter, Martin A; Briel, Matthias; Christ-Crain, Mirjam; Bonnema, Steen J; Connell, John; Cooper, David S; Bucher, Heiner C; Müller-Brand, Jan; Müller, Beat

2007-03-10

To determine the effect of adjunctive antithyroid drugs on the risk of treatment failure, hypothyroidism, and adverse events after radioiodine treatment. Meta-analysis. Electronic databases (Cochrane central register of controlled trials, Medline, Embase) searched to August 2006 and contact with experts. Review methods Three reviewers independently assessed trial eligibility and quality. Pooled relative risks for treatment failure and hypothyroidism after radioiodine treatment with and without adjunctive antithyroid drugs were calculated with a random effects model. We identified 14 relevant randomised controlled trials with a total of 1306 participants. Adjunctive antithyroid medication was associated with an increased risk of treatment failure (relative risk 1.28, 95% confidence interval 1.07 to 1.52; P=0.006) and a reduced risk for hypothyroidism (0.68, 0.53 to 0.87; P=0.006) after radioiodine treatment. We found no difference in summary estimates for the different antithyroid drugs or for whether antithyroid drugs were given before or after radioiodine treatment. Antithyroid drugs potentially increase rates of failure and reduce rates of hypothyroidism if they are given in the week before or after radioiodine treatment, respectively.

The pressor response to water drinking in humans : a sympathetic reflex?

NASA Technical Reports Server (NTRS)

Jordan, J.; Shannon, J. R.; Black, B. K.; Ali, Y.; Farley, M.; Costa, F.; Diedrich, A.; Robertson, R. M.; Biaggioni, I.; Robertson, D.

2000-01-01

BACKGROUND: Water drinking increases blood pressure profoundly in patients with autonomic failure and substantially in older control subjects. The mechanism that mediates this response is not known. METHODS AND RESULTS: We studied the effect of drinking tap water on seated blood pressure in 47 patients with severe autonomic failure (28 multiple system atrophy [MSA], 19 pure autonomic failure patients [PAF]). Eleven older controls and 8 young controls served as control group. We also studied the mechanisms that could increase blood pressure with water drinking. Systolic blood pressure increased profoundly with water drinking, reaching a maximum of 33+/-5 mm Hg in MSA and 37+/-7 in PAF mm Hg after 30 to 35 minutes. The pressor response was greater in patients with more retained sympathetic function and was almost completely abolished by trimethaphan infusion. Systolic blood pressure increased by 11+/-2.4 mm Hg in elderly but not in young controls. Plasma norepinephrine increased in both groups. Plasma renin activity, vasopressin, and blood volume did not change in any group. CONCLUSIONS: Water drinking significantly and rapidly raises sympathetic activity. Indeed, it raises plasma norepinephrine as much as such classic sympathetic stimuli as caffeine and nicotine. This effect profoundly increases blood pressure in autonomic failure patients, and this effect can be exploited to improve symptoms due to orthostatic hypotension. Water drinking also acutely raises blood pressure in older normal subjects. The pressor effect of oral water is an important yet unrecognized confounding factor in clinical studies of pressor agents and antihypertensive medications.

Are the effects of drugs to prevent and to treat heart failure always concordant? The statin paradox and its implications for understanding the actions of antidiabetic medications.

PubMed

Packer, Milton

2018-03-22

Most treatments for chronic heart failure are effective both in preventing its onset and reducing its progression. However, statins prevent the development of heart failure, but they do not decrease morbidity and mortality in those with established heart failure. This apparent discordance cannot be explained by an effect to prevent interval myocardial infarctions. Instead, it seems that the disease that statins were preventing in trials of patients with a metabolic disorder was different from the disease that they were treating in trials of chronic heart failure. The most common phenotype of heart failure in patients with obesity and diabetes is heart failure with a preserved ejection fraction (HFpEF). In this disorder, the anti-inflammatory effects of statins might ameliorate myocardial fibrosis and cardiac filling abnormalities, but these actions may have little relevance to patients with heart failure and a reduced ejection fraction (HFrEF), whose primary derangement is cardiomyocyte loss and stretch. These distinctions may explain why statins were ineffective in trials that focused on HFrEF, but have been reported to produce with favourable effects in observational studies of HFpEF. Similarly, selective cytokine antagonists were ineffective in HFrEF, but have been associated with benefits in HFpEF. These observations may have important implications for our understanding of the effects of antihyperglycaemic medications. Glucagon-like peptide-1 receptor agonists have had neutral effects on heart failure events in people at risk for HFpEF, but have exerted deleterious actions in HFrEF. Similarly, sodium-glucose co-transporter 2 inhibitors, which exert anti-inflammatory effects and reduce heart failure events in patients who are prone to HFpEF, may not be effective in HFrEF. The distinctions between HFrEF and HFpEF may explain why the effects of drugs on heart failure events in diabetes trials may not be relevant to their use in patients with systolic dysfunction. © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.

Natriuretic peptide-guided management in heart failure.

PubMed

Chioncel, Ovidiu; Collins, Sean P; Greene, Stephen J; Ambrosy, Andrew P; Vaduganathan, Muthiah; Macarie, Cezar; Butler, Javed; Gheorghiade, Mihai

2016-08-01

Heart failure is a clinical syndrome that manifests from various cardiac and noncardiac abnormalities. Accordingly, rapid and readily accessible methods for diagnosis and risk stratification are invaluable for providing clinical care, deciding allocation of scare resources, and designing selection criteria for clinical trials. Natriuretic peptides represent one of the most important diagnostic and prognostic tools available for the care of heart failure patients. Natriuretic peptide testing has the distinct advantage of objectivity, reproducibility, and widespread availability.The concept of tailoring heart failure management to achieve a target value of natriuretic peptides has been tested in various clinical trials and may be considered as an effective method for longitudinal biomonitoring and guiding escalation of heart failure therapies with overall favorable results.Although heart failure trials support efficacy and safety of natriuretic peptide-guided therapy as compared with usual care, the relationship between natriuretic peptide trajectory and clinical benefit has not been uniform across the trials, and certain subgroups have not shown robust benefit. Furthermore, the precise natriuretic peptide value ranges and time intervals of testing are still under investigation. If natriuretic peptides fail to decrease following intensification of therapy, further work is needed to clarify the optimal pharmacologic approach. Despite decreasing natriuretic peptide levels, some patients may present with other high-risk features (e.g. elevated troponin). A multimarker panel investigating multiple pathological processes will likely be an optimal alternative, but this will require prospective validation.Future research will be needed to clarify the type and magnitude of the target natriuretic peptide therapeutic response, as well as the duration of natriuretic peptide-guided therapy in heart failure patients.

Impact of transmission intensity on the accuracy of genotyping to distinguish recrudescence from new infection in antimalarial clinical trials.

PubMed

Greenhouse, Bryan; Dokomajilar, Christian; Hubbard, Alan; Rosenthal, Philip J; Dorsey, Grant

2007-09-01

Antimalarial clinical trials use genotyping techniques to distinguish new infection from recrudescence. In areas of high transmission, the accuracy of genotyping may be compromised due to the high number of infecting parasite strains. We compared the accuracies of genotyping methods, using up to six genotyping markers, to assign outcomes for two large antimalarial trials performed in areas of Africa with different transmission intensities. We then estimated the probability of genotyping misclassification and its effect on trial results. At a moderate-transmission site, three genotyping markers were sufficient to generate accurate estimates of treatment failure. At a high-transmission site, even with six markers, estimates of treatment failure were 20% for amodiaquine plus artesunate and 17% for artemether-lumefantrine, regimens expected to be highly efficacious. Of the observed treatment failures for these two regimens, we estimated that at least 45% and 35%, respectively, were new infections misclassified as recrudescences. Increasing the number of genotyping markers improved the ability to distinguish new infection from recrudescence at a moderate-transmission site, but using six markers appeared inadequate at a high-transmission site. Genotyping-adjusted estimates of treatment failure from high-transmission sites may represent substantial overestimates of the true risk of treatment failure.

Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: design and rationale of the ROADMAP clinical trial.

PubMed

Rogers, Joseph G; Boyle, Andrew J; O'Connell, John B; Horstmanshof, Douglas A; Haas, Donald C; Slaughter, Mark S; Park, Soon J; Farrar, David J; Starling, Randall C

2015-02-01

Mechanical circulatory support is now a proven therapy for the treatment of patients with advanced heart failure and cardiogenic shock. The role for this therapy in patients with less severe heart failure is unknown. The objective of this study is to examine the impact of mechanically assisted circulation using the HeartMate II left ventricular assist device in patients who meet current US Food and Drug Administration-defined criteria for treatment but are not yet receiving intravenous inotropic therapy. This is a prospective, nonrandomized clinical trial of 200 patients treated with either optimal medical management or a mechanical circulatory support device. This trial will be the first prospective clinical evaluation comparing outcomes of patients with advanced ambulatory heart failure treated with either ongoing medical therapy or a left ventricular assist device. It is anticipated to provide novel insights regarding relative outcomes with each treatment and an understanding of patient and provider acceptance of the ventricular assist device therapy. This trial will also provide information regarding the risk of events in "stable" patients with advanced heart failure and guidance for the optimal timing of left ventricular assist device therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Hemodynamic changes during weaning: can we assess and predict cardiac-related weaning failure by transthoracic echocardiography?

PubMed Central

2010-01-01

Cardiac-related failure of weaning from mechanical ventilation is an important reason for prolonged mechanical ventilation, intensive care unit treatment, and increased morbidity and mortality. When transthoracic echocardiography (TTE) is routinely performed before a weaning trial, patients at high risk of cardiac-related failure can be detected by low left ventricular (LV) ejection fraction, diastolic dysfunction, and elevated LV filling pressure. During the weaning trial, a further increase of LV filling pressure and progression of diastolic failure can be observed by repeated TTE. Owing to certain limitations concerning patients and methodology, TTE cannot be employed in every patient and invasive hemodynamic monitoring is still mandatory in selected patients with repetitive weaning failure. PMID:20619005

Hemodynamic changes during weaning: can we assess and predict cardiac-related weaning failure by transthoracic echocardiography?

PubMed

Voga, Gorazd

2010-01-01

Cardiac-related failure of weaning from mechanical ventilation is an important reason for prolonged mechanical ventilation, intensive care unit treatment, and increased morbidity and mortality. When transthoracic echocardiography (TTE) is routinely performed before a weaning trial, patients at high risk of cardiac-related failure can be detected by low left ventricular (LV) ejection fraction, diastolic dysfunction, and elevated LV filling pressure. During the weaning trial, a further increase of LV filling pressure and progression of diastolic failure can be observed by repeated TTE. Owing to certain limitations concerning patients and methodology, TTE cannot be employed in every patient and invasive hemodynamic monitoring is still mandatory in selected patients with repetitive weaning failure.

The 'aerobic/resistance/inspiratory muscle training hypothesis in heart failure'.

PubMed

Laoutaris, Ioannis D

2018-01-01

Evidence from large multicentre exercise intervention trials in heart failure patients, investigating both moderate continuous aerobic training and high intensity interval training, indicates that the 'crème de la crème' exercise programme for this population remains to be found. The 'aerobic/resistance/inspiratory (ARIS) muscle training hypothesis in heart failure' is introduced, suggesting that combined ARIS muscle training may result in maximal exercise pathophysiological and functional benefits in heart failure patients. The hypothesis is based on the decoding of the 'skeletal muscle hypothesis in heart failure' and on revision of experimental evidence to date showing that exercise and functional intolerance in heart failure patients are associated not only with reduced muscle endurance, indication for aerobic training (AT), but also with reduced muscle strength and decreased inspiratory muscle function contributing to weakness, dyspnoea, fatigue and low aerobic capacity, forming the grounds for the addition of both resistance training (RT) and inspiratory muscle training (IMT) to AT. The hypothesis will be tested by comparing all potential exercise combinations, ARIS, AT/RT, AT/IMT, AT, evaluating both functional and cardiac indices in a large sample of heart failure patients of New York Heart Association class II-III and left ventricular ejection fraction ≤35% ad hoc by the multicentre randomized clinical trial, Aerobic Resistance, InSpiratory Training OutcomeS in Heart Failure (ARISTOS-HF trial).

Eprosartan-based hypertension therapy, systolic arterial blood pressure and cognitive function: analysis of Middle East data from the OSCAR study.

PubMed

Radaideh, Ghazi Ahmad; Choueiry, Patrick; Ismail, Amr; Eid, Elie; Berrou, Jean-Pascal; Sedefdjian, Armand; Sévenier, Frank; Pathak, Atul

2011-01-01

Studies have indicated a relationship between hypertension and cognitive function. The possible effect of antihypertensive therapy on cognitive disorders is therefore a matter of interest. The Observational Study on Cognitive function And SBP Reduction (OSCAR) was an open-label, multinational trial designed to evaluate the impact of eprosartan-based antihypertensive therapy on cognitive function in patients with essential hypertension. Eprosartan 600 mg/day for 6 months (with provision for additional medication as needed) was initiated in hypertensive subjects aged ≥ 50 years. A total of 853 patients in an intention-to-treat cohort from seven countries of the Middle East was identified for subgroup analysis. Arterial blood pressure was reduced significantly (P < 0.001) during the study: At the end of 6 months of eprosartan-based therapy, the mean (±SD) reduction from baseline was 32.1 ± 14.3/14.6.3 ± 8.6 mmHg (P < 0.001). Mean pulse pressure was reduced by 18.3 ± 13.1 mmHg (P < 0.0001 vs baseline). Blood pressure was normalized (systolic <140 mmHg and diastolic <90 mmHg) in 68.2% of patients. The overall mean Mini-Mental State Examination (MMSE) score after 6 months of eprosartan-based therapy was one-point higher than at baseline (P < 0.001). MMSE score on completion of 6 months' follow-up was either unchanged or increased from baseline in 793 (93%) individuals and decreased in 60 (7%). Factors associated with stability of or improvement in cognitive function included MMSE score at baseline, diastolic blood pressure (DBP) at baseline, and treatment-induced change in DBP. Results from the Middle East subgroup of OSCAR are supportive of the hypothesis that antihypertensive therapy based on angiotensin-receptor blocker therapy with eprosartan may be associated with preservation or improvement of cognitive function.

Psychological predictors of the antihypertensive effects of music-guided slow breathing.

PubMed

Modesti, Pietro Amedeo; Ferrari, Antonella; Bazzini, Cristina; Costanzo, Giusi; Simonetti, Ignazio; Taddei, Stefano; Biggeri, Annibale; Parati, Gianfranco; Gensini, Gian Franco; Sirigatti, Saulo

2010-05-01

The possibility that daily sessions of music-guided slow breathing may reduce 24-h ambulatory blood pressure (ABP), and predictors of efficacy were explored in a randomized, placebo-controlled trial with parallel design. Age-matched and sex-matched hypertensive patients were randomized to music-guided slow breathing exercises (4-6 breaths/min; 1: 2 ratio of inspiration: expiration duration) (Intervention; n = 29) or to control groups who were thought to relax while either listening to slow music (Control-M; n = 26) or reading a book (Control-R; n = 31). At baseline and at follow-up visits (1 week and 1, 3 and 6 months), ABP monitoring was performed. At mixed model analysis, intervention was associated with a significant reduction of 24-h (P = 0.001) and night-time (0100-0600 h) (P < 0.0001) systolic ABP. The average reduction of systolic 24-h ABP at 6 months was 4.6 mmHg [confidence limits at 95% 1.93-7.35] and 4.1 mmHg (95% confidence limits 1.59-6.67) vs. Control-M and Control-R groups, respectively, (P < 0.001 for both). Antihypertensive treatment was selected as negative predictor of BP reduction at multivariate stepwise analysis. When antihypertensive treatment was inserted as covariate in a generalized linear model, psychological subscales assessed at baseline by the Mental Health Inventory questionnaire were found to affect systolic blood pressure reduction at 6-month follow-up (general positive affect P < 0.001; emotional ties, P < 0.001; loss of behavioral control, P = 0.035). In particular, a level of general positive affect higher than the 75th percentiles was found to be significantly associated with low treatment efficacy (odds ratio 0.09; 95% confidence limits 0.01-0.93). Daily sessions of voluntary music-guided slow breathing significantly reduce 24-h systolic ABP, and psychological predictors of efficacy can be identified.

THE ANTIHYPERTENSIVE EFFECTS OF AEROBIC VERSUS ISOMETRIC HANDGRIP RESISTANCE EXERCISE

PubMed Central

ASH, Garrett I.; TAYLOR, Beth A.; THOMPSON, Paul D.; MACDONALD, Hayley V.; LAMBERTI, Lauren; CHEN, Ming-Hui; FARINATTI, Paulo; KRAEMER, William J.; PANZA, Gregory A.; ZALESKI, Amanda L.; DESHPANDE, Ved; BALLARD, Kevin D.; MUJTABA, Mohammadtokir; WHITE, C. Michael; PESCATELLO, Linda S.

2017-01-01

Aerobic exercise reduces blood pressure (BP) on average 5 to 7 mmHg among those with hypertension; limited evidence suggests similar or even greater BP benefits may result from isometric handgrip (IHG) resistance exercise. We conducted a randomized controlled trial investigating the antihypertensive effects of an acute bout of aerobic compared to IHG exercise in the same individuals. Middle-aged adults (n=27) with prehypertension and obesity randomly completed three experiments: aerobic [60% peak oxygen uptake, 30 minutes]; IHG [30% maximum voluntary contraction, 4x2 minutes bilateral]; and non-exercise control. Subjects were assessed for carotid-femoral pulse wave velocity (PWV) pre and post exercise, and left the laboratory wearing an ambulatory BP monitor. Systolic and diastolic BP (SBP/DBP) were lower after aerobic versus IHG (4.8±1.8/3.1±1.3mmHg, p=0.01/0.04) and control (5.6±1.8/3.6±1.3mmHg, p=0.02/0.04) over the awake hours, with no difference between IHG versus control (p=0.80/0.83). PWV changes following acute exercise did not differ by modality (aerobic increased 0.01±0.21m•s−1, IHG decreased 0.06±0.15m•s−1, control increased 0.25±0.17m•s−1, p>0.05). A subset of participants then completed either 8 weeks of aerobic or IHG training. Awake SBP was lower after versus before aerobic training (7.6±3.1mmHg, p=0.02), while sleep DBP was higher after IHG training (7.7±2.3mmHg, p=0.02). Our findings did not support IHG as antihypertensive therapy but that aerobic exercise should continue to be recommended as the primary exercise modality for its immediate and sustained BP benefits. PMID:27861249

Effects of Demographics on the Antihypertensive Efficacy of Triple Therapy With Amlodipine, Valsartan, and Hydrochlorothiazide for Moderate to Severe Hypertension

PubMed Central

Calhoun, David A.; Lacourci00E8;re, Yves; Crikelair, Nora; Jia, Yan; Glazer, Robert D.

2014-01-01

Objective To compare the antihypertensive efficacy and safety of once-daily triple therapy with amlodipine (Aml) 10 mg, valsartan (Val) 320 mg, and hydrochlorothiazide (HCTZ) 25 mg versus dual-therapy combinations of these components in patients with moderate to severe hypertension. Research design Subgroup analysis of a multinational, randomized, double-blind, parallel-group, active-controlled trial. Methods After antihypertensive washout and a placebo run-in of up to 4 weeks, 2271 patients were randomly allocated in a 1:1:1:1 ratio to receive Aml/Val/HCTZ triple therapy or dual therapy with Val/HCTZ, Aml/Val, or Aml/HCTZ for 8 weeks. Forced titration to the full dose was done over the first 2 weeks of treatment. Efficacy and safety parameters were determined by age group (<65 vs. ≥65 years), gender, race (White vs. Black), ethnicity (Hispanic/Latino vs. non-Hispanic/Latino), and body mass index (BMI, <30 vs. ≥30 kg/m2). Main outcome measures Change from baseline to endpoint in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP); blood pressure (BP) control rate <140/90 mmHg. Results Triple therapy was numerically superior and, for the majority of comparisons, statistically superior to each dual therapy in reducing MSSBP and MSDBP and in improving BP control rates in all subgroups. Across subgroups, triple therapy reduced MSSBP by 5.7–10.7 mmHg more than Val/HCTZ, 3.4–8.3 mmHg more than Aml/Val, and 4.4–9.4 mmHg more than Aml/HCTZ. Triple therapy was well tolerated across all subgroups. Limitations of our analysis included the lack of stratification of patients by subgroup at randomization and the small sample size of some subgroups (eg, Blacks, elderly). Conclusions Triple therapy with Aml/Val/HCTZ is effective and well tolerated in patients with moderate to severe hypertension regardless of age, gender, race, ethnicity, or BMI. PMID:23721363

pRotective vEntilation with veno-venouS lung assisT in respiratory failure: A protocol for a multicentre randomised controlled trial of extracorporeal carbon dioxide removal in patients with acute hypoxaemic respiratory failure.

PubMed

McNamee, J J; Gillies, M A; Barrett, N A; Agus, A M; Beale, R; Bentley, A; Bodenham, A; Brett, S J; Brodie, D; Finney, S J; Gordon, A J; Griffiths, M; Harrison, D; Jackson, C; McDowell, C; McNally, C; Perkins, G D; Tunnicliffe, W; Vuylsteke, A; Walsh, T S; Wise, M P; Young, D; McAuley, D F

2017-05-01

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO 2 R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO 2 R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO 2 R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO 2 R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

The first multicenter, randomized, controlled trial of home telemonitoring for Japanese patients with heart failure: home telemonitoring study for patients with heart failure (HOMES-HF).

PubMed

Kotooka, Norihiko; Kitakaze, Masafumi; Nagashima, Kengo; Asaka, Machiko; Kinugasa, Yoshiharu; Nochioka, Kotaro; Mizuno, Atsushi; Nagatomo, Daisuke; Mine, Daigo; Yamada, Yoko; Kuratomi, Akiko; Okada, Norihiro; Fujimatsu, Daisuke; Kuwahata, So; Toyoda, Shigeru; Hirotani, Shin-Ichi; Komori, Takahiro; Eguchi, Kazuo; Kario, Kazuomi; Inomata, Takayuki; Sugi, Kaoru; Yamamoto, Kazuhiro; Tsutsui, Hiroyuki; Masuyama, Tohru; Shimokawa, Hiroaki; Momomura, Shin-Ichi; Seino, Yoshihiko; Sato, Yasunori; Inoue, Teruo; Node, Koichi

2018-02-15

Home telemonitoring is becoming more important to home medical care for patients with heart failure. Since there are no data on home telemonitoring for Japanese patients with heart failure, we investigated its effect on cardiovascular outcomes. The HOMES-HF study was the first multicenter, open-label, randomized, controlled trial (RCT) to elucidate the effectiveness of home telemonitoring of physiological data, such as body weight, blood pressure, and pulse rate, for Japanese patients with heart failure (UMIN Clinical Trials Registry 000006839). The primary end-point was a composite of all-cause death or rehospitalization due to worsening heart failure. We analyzed 181 recently hospitalized patients with heart failure who were randomly assigned to a telemonitoring group (n = 90) or a usual care group (n = 91). The mean follow-up period was 15 (range 0-31) months. There was no statistically significant difference in the primary end-point between groups [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.548-1.648; p = 0.572]. Home telemonitoring for Japanese patients with heart failure was feasible; however, beneficial effects in addition to those of usual care were not demonstrated. Further investigation of more patients with severe heart failure, participation of home medical care providers, and use of a more integrated home telemonitoring system emphasizing communication as well as monitoring of symptoms and physiological data are required.

Appropriate and inappropriate use of dronedarone in 2013.

PubMed

Naccarelli, Gerald V

2013-08-01

Dronedarone is a multichannel blocking antiarrhythmic agent that has been shown to prevent atrial fibrillation/flutter (AF/AFl) recurrences in several multi-center trials. In the ANDROMEDA trial, dronedarone treatment increased mortality and cardiovascular hospitalizations patients with decompensated heart failure. In the ATHENA trial, dronedarone was used in elderly high risk patients with paroxysmal or persistent AF/AFl, excluding those with advanced heart failure, cardiovascular hospitalizations were significantly reduced. Dronedarone increased mortality and cardiovascular hospitalizations in a different patient group with permanent AF/AFl. Although organic toxicity from the drug is very rare, post-marketing data has reported rare hepatic toxicity associated with dronedarone use. Current guidelines position dronedarone as a front-line antiarrhythmic in many patients with AF/Fl. However, dronedarone should not be used in patients with advanced heart failure or in permanent AF. Clinical trial results have helped us define appropriate and inappropriate candidates for dronedarone.

The association of antihypertensives with postural blood pressure and falls among seniors residing in the community: a case-control study.

PubMed

Zia, Anam; Kamaruzzaman, Shahrul B; Myint, Phyo K; Tan, Maw P

2015-10-01

A drop in postural blood pressure (BP) may contribute to falls, while antihypertensives have been considered to induce postural drop or orthostatic hypotension (OH) and falls among older people. However, this relationship between antihypertensives, postural BP and the risk of falls has never been evaluated in a single study. To examine the association of postural BP changes and BP therapy with the risk of falls among community-dwelling older people in a case-control manner. Cases (n = 202) included participants aged ≥ 65 years with two falls or one injurious fall while controls (n = 156) included participants ≥ 65 years with no falls in the preceding 12 months. Antihypertensives usage and medical history were recorded. Supine BP measurements were obtained at 10 min rest and at 1, 2 and 3 min after standing. Orthostatic hypotension was defined as a reduction in BP of 20/10 mmHg within 3 min of standing. Individual antihypertensive classes were not associated with falls. Minimal standing systolic BP (SBP) was significantly lower among fallers [128 (± 27·3) vs. 135·7 (± 24·7) mmHg; P = 0·01], but fallers were not more likely to fulfil the diagnostic criteria for OH. Diuretics were associated with OH and α-blockers were associated with minimal standing SBP. Univariate analysis revealed that the use of ≥ 2 antihypertensives was associated with recurrent and injurious falls [OR,1.97;CI,1.2-3.1], which was no longer significant aftermultivariateadjustment for age and number of comorbidities [OR, 1.6; CI, 0.95-2.6]. Minimal standing SBP or a lower SBP at 2 or 3minutes standing was associated with falls rather than OH using consensus definition. Association between ≥ 2 antihypertensives and falls was attenuated by increasing age and comorbidities. Our findings challenge previous assumptions that OH or the use of antihypertensives is associated with falls. Future studies should now seek to link these findings prospectively with falls in order to guide decision-making for BP lowering therapy among older patients. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

The CardiAMP Heart Failure trial: A randomized controlled pivotal trial of high-dose autologous bone marrow mononuclear cells using the CardiAMP cell therapy system in patients with post-myocardial infarction heart failure: Trial rationale and study design.

PubMed

Raval, Amish N; Cook, Thomas D; Duckers, Henricus J; Johnston, Peter V; Traverse, Jay H; Abraham, William T; Altman, Peter A; Pepine, Carl J

2018-07-01

Heart failure following myocardial infarction is a common, disabling, and deadly condition. Direct injection of autologous bone marrow mononuclear cells into the myocardium may result in improved functional recovery, relieve symptoms, and improve other cardiovascular outcomes. CardiAMP-HF is a randomized, double-blind, sham-controlled, pivotal trial designed to investigate the safety and efficacy of autologous bone marrow mononuclear cells treatment for patients with medically refractory and symptomatic ischemic cardiomyopathy. The primary end point is change in 6-minute walk distance adjusted for major adverse cardiovascular events at 12 months following treatment. Particularly novel aspects of this trial include a cell potency assay to screen subjects who have bone marrow cell characteristics that suggest a favorable response to treatment, a point-of-care treatment method, a high target dose of 200 million cells, and an efficient transcatheter intramyocardial delivery method that is associated with high cell retention. This novel approach may lead to a new treatment for those with ischemic heart disease suffering from medically refractory heart failure. Copyright © 2018 Elsevier Inc. All rights reserved.

Failure Rate of Direct High-Viscosity Glass-Ionomer Versus Hybrid Resin Composite Restorations in Posterior Permanent Teeth - a Systematic Review

PubMed Central

Mickenautsch, Steffen; Yengopal, Veerasamy

2015-01-01

Purpose Traditionally, resin composite restorations are claimed by reviews of the dental literature as being superior to glass-ionomer fillings in terms of restoration failures in posterior permanent teeth. The aim of this systematic review is to answer the clinical question, whether conventional high-viscosity glass-ionomer restorations, in patients with single and/or multi-surface cavities in posterior permanent teeth, have indeed a higher failure rate than direct hybrid resin composite restorations. Methods Eight databases were searched until December 02, 2013. Trials were assessed for bias risks, in-between datasets heterogeneity and statistical sample size power. Effects sizes were computed and statistically compared. A total of 55 citations were identified through systematic literature search. From these, 46 were excluded. No trials related to high-viscosity glass-ionomers versus resin composite restorations for direct head-to-head comparison were found. Three trials related to high-viscosity glass-ionomers versus amalgam and three trials related to resin composite versus amalgam restorations could be included for adjusted indirect comparison, only. Results The available evidence suggests no difference in the failure rates between both types of restoration beyond the play of chance, is limited by lack of head-to-head comparisons and an insufficient number of trials, as well as by high bias and in-between-dataset heterogeneity risk. The current clinical evidence needs to be regarded as too poor in order to justify superiority claims regarding the failure rates of both restoration types. Sufficiently large-sized, parallel-group, randomised control trials with high internal validity are needed, in order to justify any clinically meaningful judgment to this topic. PMID:26962372

Usefulness of radiological signs of pulmonary congestion in predicting failed spontaneous breathing trials

PubMed Central

Antonio, Ana Carolina Peçanha; Teixeira, Cassiano; Castro, Priscylla Souza; Zanardo, Ana Paula; Gazzana, Marcelo Basso; Knorst, Marli

2017-01-01

ABSTRACT Objective: Inspiratory fall in intrathoracic pressure during a spontaneous breathing trial (SBT) may precipitate cardiac dysfunction and acute pulmonary edema. We aimed to determine the relationship between radiological signs of pulmonary congestion prior to an SBT and weaning outcomes. Methods: This was a post hoc analysis of a prospective cohort study involving patients in an adult medical-surgical ICU. All enrolled individuals met the eligibility criteria for liberation from mechanical ventilation. Tracheostomized subjects were excluded. The primary endpoint was SBT failure, defined as the inability to tolerate a T-piece trial for 30-120 min. An attending radiologist applied a radiological score on interpretation of digital chest X-rays performed before the SBT. Results: A total of 170 T-piece trials were carried out; SBT failure occurred in 28 trials (16.4%), and 133 subjects (78.3%) were extubated at first attempt. Radiological scores were similar between SBT-failure and SBT-success groups (median [interquartile range] = 3 [2-4] points vs. 3 [2-4] points; p = 0.15), which, according to the score criteria, represented interstitial lung congestion. The analysis of ROC curves demonstrated poor accuracy (area under the curve = 0.58) of chest x-rays findings of congestion prior to the SBT for discriminating between SBT failure and SBT success. No correlation was found between fluid balance in the 48 h preceding the SBT and radiological score results (ρ = −0.13). Conclusions: Radiological findings of pulmonary congestion should not delay SBT indication, given that they did not predict weaning failure in the medical-surgical critically ill population. (ClinicalTrials.gov identifier: NCT02022839 [http://www.clinicaltrials.gov/]) PMID:29364998

Exercise Training for Heart Failure Patients with and without Systolic Dysfunction: An Evidence-Based Analysis of How Patients Benefit

PubMed Central

Smart, Neil

2011-01-01

Significant benefits can be derived by heart failure patients from exercise training. This paper provides an evidence-based assessment of expected clinical benefits of exercise training for heart failure patients. Meta-analyses and randomized, controlled trials of exercise training in heart failure patients were reviewed from a search of PubMed, Cochrane Controlled Trial Registry (CCTR), CINAHL, and EMBASE. Exercise training improves functional capacity, quality of life, hospitalization, and systolic and diastolic function in heart failure patients. Heart failure patients with preserved systolic function (HFnEF) participating in exercise training studies are more likely to be women and are 5–7 years older than their systolic heart failure (CHF) counterparts. All patients exhibit low functional capacities, although in HFnEF patients this may be age related, therefore subtle differences in exercise prescriptions are required. Published works report that exercise training is beneficial for heart failure patients with and without systolic dysfunction. PMID:20953365

Implantable Hemodynamic Monitoring for Heart Failure Patients.

PubMed

Abraham, William T; Perl, Leor

2017-07-18

Rates of heart failure hospitalization remain unacceptably high. Such hospitalizations are associated with substantial patient, caregiver, and economic costs. Randomized controlled trials of noninvasive telemedical systems have failed to demonstrate reduced rates of hospitalization. The failure of these technologies may be due to the limitations of the signals measured. Intracardiac and pulmonary artery pressure-guided management has become a focus of hospitalization reduction in heart failure. Early studies using implantable hemodynamic monitors demonstrated the potential of pressure-based heart failure management, whereas subsequent studies confirmed the clinical utility of this approach. One large pivotal trial proved the safety and efficacy of pulmonary artery pressure-guided heart failure management, showing a marked reduction in heart failure hospitalizations in patients randomized to active pressure-guided management. "Next-generation" implantable hemodynamic monitors are in development, and novel approaches for the use of this data promise to expand the use of pressure-guided heart failure management. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Intermittent hypoxia training as non-pharmacologic therapy for cardiovascular diseases: Practical analysis on methods and equipment

PubMed Central

Serebrovskaya, Tatiana V

2016-01-01

The global industrialization has brought profound lifestyle changes and environmental pollutions leading to higher risks of cardiovascular diseases. Such tremendous challenges outweigh the benefits of major advances in pharmacotherapies (such as statins, antihypertensive, antithrombotic drugs) and exacerbate the public healthcare burdens. One of the promising complementary non-pharmacologic therapies is the so-called intermittent hypoxia training (IHT) via activation of the human body's own natural defense through adaptation to intermittent hypoxia. This review article primarily focuses on the practical questions concerning the utilization of IHT as a non-pharmacologic therapy against cardiovascular diseases in humans. Evidence accumulated in the past five decades of research in healthy men and patients has suggested that short-term daily sessions consisting 3–4 bouts of 5–7 min exposures to 12–10% O2 alternating with normoxic durations for 2–3 weeks can result in remarkable beneficial effects in treatment of cardiovascular diseases such as hypertension, coronary heart disease, and heart failure. Special attentions are paid to the therapeutic effects of different IHT models, along with introduction of a variety of specialized facilities and equipment available for IHT, including hypobaric chambers, hypoxia gas mixture deliver equipment (rooms, tents, face masks), and portable rebreathing devices. Further clinical trials and thorough evaluations of the risks versus benefits of IHT are much needed to develop a series of standardized and practical guidelines for IHT. Taken together, we can envisage a bright future for IHT to play a more significant role in the preventive and complementary medicine against cardiovascular diseases. PMID:27407098

Azilsartan: a newly approved angiotensin II receptor blocker.

PubMed

Lam, Sum

2011-01-01

Hypertension is a common chronic disease that leads to significant cardiovascular morbidity and mortality. Blood pressure control is essential to prevent end-organ complications, such as stroke, myocardial infarction, heart failure, or kidney disease. Azilsartan is the eighth angiotensin II receptor blocker approved for the management of hypertension, alone or in combination with other agents. At the approved dosage, it reduces systolic blood pressure by 12 to 15 mm Hg and diastolic blood pressure by 7 to 8 mm Hg. A higher dose of azilsartan (80 mg) was superior to valsartan 320 mg or olmesartan 40 mg in lowering systolic blood pressure in short-term studies. Additional blood pressure reduction is expected when azilsartan is used adjunctively with a diuretic. However, the effects of azilsartan on cardiovascular morbidity or mortality are still lacking. Azilsartan is well tolerated; the most common side effects are headache and diarrhea. No cases of hyperkalemia have been reported in 6-week clinical trials. Worsening of renal function and hypotension should be monitored, particularly in those with baseline risk factors. It is unknown whether azilsartan would join angiotensin-converting enzyme inhibitors and other angiotensin receptor blockers as the preferred hypertensive agents for end-organ protection. At this time, azilsartan should be considered as an alternative agent for mild-to-moderate hypertension, or as an adjunctive therapy when preferred agents fail to maintain optimal blood pressure control. It is also an option for those patients who have contraindications or cannot tolerate other antihypertensive agents, including dry cough induced by angiotensin-converting enzyme inhibitors.

Azilsartan/chlorthalidone combination therapy for blood pressure control.

PubMed

Cheng, Judy Wm

2013-01-01

Edarbyclor(®) is a combined angiotensin receptor blocker (ARB) and thiazide-like diuretic (azilsartan and chlorthalidone), and was approved on December 20, 2011 by the US Food and Drug Administration (FDA) for hypertension management. To review the pharmacology, pharmacokinetics, efficacy, safety, tolerability, and role of azilsartan plus chlorthalidone for hypertension management. Peer-reviewed clinical trials, review articles, and relevant treatment guidelines, were identified from the databases MEDLINE and Current Contents (both 1966 to February 15, 2013, inclusive) using search terms "azilsartan", "chlorthalidone", "pharmacology", "pharmacokinetics", "pharmacodynamics", "pharmacoeconomics", and "cost-effectiveness". The FDA website, as well as manufacturer prescribing information, was also reviewed to identify other relevant information. Azilsartan is a new ARB with high affinity for the angiotensin 1 receptor, approved by the FDA for hypertension management. Unlike other ARBs, azilsartan has no clinical data supporting improvement in cardiovascular outcomes, and is not approved for indications other than hypertension, which a select few other ARBs may be used for (eg, diabetic nephropathy and heart failure). Chlorthalidone is a longer acting thiazide-like diuretic that has been demonstrated to improve cardiovascular outcomes. Combination treatment with azilsartan/chlorthalidone is effective for reducing blood pressure. Compared to olmesartan/hydrochlorothiazide and azilsartan/hydrochlorothiazide combinations, azilsartan/chlorthalidone appears to be more efficacious for reducing blood pressure. Azilsartan/chlorthalidone can be considered an antihypertensive therapy option in patients for whom combination therapy is required (blood pressure >20 mmHg systolic or >10 mmHg diastolic above goal). Cost to patients and insurance coverage will probably determine whether azilsartan/chlorthalidone will be the most appropriate combination therapy for an individual patient.

What have we learned from the current trials?

PubMed

Abbott, Kevin C; Bakris, George L

2004-01-01

Even well-conducted randomized controlled trials can only reduce uncertainty, not eliminate it. The trials presented in this article all have gaps, and like many studies, some raise more questions than answers. A summary of the current trials, however, can be presented as follows. For patients with essential hypertension who are at high risk for cardiovascular disease, the use of diuretic therapy (excluding simultaneous use of ACE or CCB) resulted in outcomes at least equivalent to the use of either ACE or CCB without diuretics. Naturally, the dilemma for clinicians is that these drugs are most often used in combination with thiazide diuretics, as indicated by the RENAAL trial where 80% of ARB were used with diuretics in patients with type II diabetes and known nephropathy. The increased risk of heart failure observed with ACE and CCB in that trial may be relevant only to patients in whom diuretics were not also used. The study does raise important awareness, however, that ACE or CCB use without diuretic therapy is no better than diuretic therapy, and may be associated with higher risk of certain outcomes. A substantial number of patients with essential hypertension might achieve adequate blood pressure control with diuretic monotherapy. If so, that certainly has important implications for the cost of medical care in this country. For African Americans with essential hypertension, ACE may have advantages as a component of therapy in comparison with CCBs or beta-blockers, although diuretics should probably be the cornerstone of therapy for them and supported by the Seventh Joint National Committee. For patients with proteinuric renal disease, whether associated with diabetes or hypertension, it should be considered inappropriate to use DHP CCB as monotherapy in any setting, whether as part of a clinical trial or in clinical practice. These drugs should not be considered as ethical placebo arms in trials, most especially in diabetic nephropathy, nor should they be used without an ACE or ARB in patients with proteinuric renal disease in the absence of documented contraindications or intolerance to ACE, ARB, or non-DHP CCB (which are now considered second-line agents for proteinuric renal disease, and are acceptable placebo or comparison arms in clinical trials). For patients with type I diabetes, ACE remain the cornerstone of therapy. Because of recent RENAAL and IDNT trial results, the greatest benefit for slowing progression of renal disease in type II diabetic nephropathy now belongs to ARBs. In contrast, however, the HOPE trial showed that ACE, specifically ramipril, had the greatest evidence for prevention of cardiovascular outcomes in patients with renal insufficiency, regardless of diabetic status. Cardiovascular outcomes were secondary end points in the RENAAL and IDNT trials, and with the exception of heart failure for losartan, no benefits on cardiovascular outcomes were statistically significant. Progression of renal disease has only been studied in a relatively small cohort of Israeli patients comparing enalapril with nifedipine. These gaps lead to a classic dilemma in medical decision-making. Because evidence has shown that patients with elevated serum creatinine (greater than or equal to 1.4 mg/dL) are just as likely to die from cardiovascular disease as they are to reach end-stage renal disease, which outcome should be the focus for clinicians, or for researchers? Using a strictly evidence-based approach, this question can only be answered by yet another large, long, randomized, controlled trial. Given the similarity of actions between the ARB and ACE, it is likely there is considerable overlap of both benefits and side-effects between the two, although ARB may have a lower incidence of cough and hyperkalemia. The decision of which antihypertensive agents to use will have to be tailored carefully to the needs of the patient and careful consideration of both medical and economic factors. Regardless of the choice between an ACE or ARB, however, post hoc analysis of clinical trials [21,47] and observational data clearly indicate that patients with chronic kidney disease, even if considered mild (ie, serum creatinine greater than or equal to 1.4 mg/dL) are at significantly greater risk of cardiovascular morbidity and mortality compared with those with better kidney function. As stated in a recent review by the authors of the HOPE trial [50], "the frequent practice of withholding ACE [or ARB] in patients with mild renal insufficiency is unwarranted," because not only are these patients precisely those who might benefit most from their use, but safety and tolerability are generally excellent. Based on the results of the AASK trial, the authors add the same for the use of ACE inhibitors in African Americans.

Dose-dependent antihypertensive efficacy and tolerability of perindopril in a large, observational, 12-week, general practice-based study.

PubMed

Tsoukas, George; Anand, Sanjiv; Yang, Kwang

2011-01-01

Current guidelines recommend the use of full therapeutic dosages of antihypertensive agents, or combination therapy, to improve BP control of hypertensive patients in primary healthcare. The aim of this study was to assess the dose-dependent antihypertensive efficacy and safety of perindopril 4 and 8 mg/day in the clinical setting. The CONFIDENCE study was a prospective, observational, multicenter trial. This was a real-world, clinic-based, outpatient study involving 880 general practitioners/primary-care clinics and 113 specialists in Canada. The study included untreated or inadequately managed patients with hypertension (i.e. seated BP ≥ 140/90 mmHg, or ≥ 130/80 mmHg in the presence of diabetes mellitus, renal disease, or proteinuria) without coronary artery disease (CAD). Treatment consisted of perindopril 4 mg/day, uptitrated to 8 mg/day as required for BP control at visit 2, for 12 weeks. Among the patients already being treated at baseline, perindopril either directly replaced all previous ACE inhibitors or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), or was added to antihypertensive treatment with calcium channel blockers (CCBs), diuretics, or β-adrenoceptor antagonists (β-blockers). The primary outcomes were the mean changes in BP from baseline following treatment with perindopril 4 and 8 mg/day as well as the proportion of patients achieving BP control (BP <140/90 mmHg, or <130/80 mmHg in diabetic patients) in the intent-to-treat (ITT) population. Secondary analyses included the incidence of adverse events and compliance. A total of 8298 hypertensive patients entered the study: 56% with newly diagnosed hypertension and 44% with uncontrolled hypertension. Mean SBP/DBP decreased significantly from baseline (152.5  ±  10.8/89.5  ±  9 mmHg) over 12 weeks (-18.5/-9.7 mmHg; p < 0.001). At visit 2, 23% of patients were uptitrated to perindopril 8 mg/day, which resulted in an additional mean 10.1/5.3 mmHg BP reduction; this reduction was even greater (15.1/5.7 mmHg) among a separate group of severely hypertensive patients (i.e. SBP >170 mmHg or DBP >109 mmHg at baseline). Target BP was achieved in 54% of the ITT population. Both perindopril 4 mg/day and perindopril 8 mg/day were well tolerated and compliance was high throughout the study. In the clinical outpatient setting, perindopril was found to be an effective dose-dependent and well tolerated antihypertensive treatment, with good compliance. Uptitration to the full therapeutic dosage of perindopril is an efficient approach for the management of a broad range of hypertensive patients without CAD.

Management of Hypertension in Diabetic Nephropathy: How Low Should We Go?

PubMed

Sternlicht, Hillel; Bakris, George L

2016-01-01

Hypertension is a frequent comorbidity often following the development of diabetic nephropathy among individuals with type 1 diabetes and affecting most patients with type 2 diabetes at the time of diagnosis. Multiple prospective randomized placebo-controlled trials demonstrate that tight blood pressure control among patients with diabetic nephropathy reduces the rates of macrovascular and microvascular complications. While randomized trials exist and support a blood pressure goal of <140/90 mm Hg for patients with nondiabetic kidney disease, there are no prospective data regarding a specific blood pressure goal on progression of diabetic nephropathy. Retrospective data analyses from trials show a linear relationship between either baseline or achieved study blood pressure and progression of nephropathy. Very high albuminuria is a hallmark of diabetic nephropathy with reductions by either angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blocker (ARB) monotherapy associated with slowed nephropathy progression. However, combination antihypertensive therapy, while decreasing proteinuria, augments the risk of hyperkalemia, hypotension, and kidney dysfunction. Given the lack of trial data for a BP goal among patients with diabetic nephropathy, prospective trials are needed to define the optimal blood pressure necessary to preserve kidney function. At present, guideline blood pressure goals of less than 140/90 mm Hg and the use of ACEi or ARB therapy for those with more than 300 mg of albuminuria are mandated. © 2016 S. Karger AG, Basel.

Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria

PubMed Central

Zani, Babalwa; Gathu, Michael; Donegan, Sarah; Olliaro, Piero L; Sinclair, David

2014-01-01

Background The World Health Organization (WHO) recommends Artemisinin-based Combination Therapy (ACT) for treating uncomplicated Plasmodium falciparum malaria. This review aims to assist the decision-making of malaria control programmes by providing an overview of the relative effects of dihydroartemisinin-piperaquine (DHA-P) versus other recommended ACTs. Objectives To evaluate the effectiveness and safety of DHA-P compared to other ACTs for treating uncomplicated P. falciparum malaria in adults and children. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled Trials (mRCT) up to July 2013. Selection criteria Randomized controlled trials comparing a three-day course of DHA-P to a three-day course of an alternative WHO recommended ACT in uncomplicated P. falciparum malaria. Data collection and analysis Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy’ and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach. Main results We included 27 trials, enrolling 16,382 adults and children, and conducted between 2002 and 2010. Most trials excluded infants aged less than six months and pregnant women. DHA-P versus artemether-lumefantrine In Africa, over 28 days follow-up, DHA-P is superior to artemether-lumefantrine at preventing further parasitaemia (PCR-unadjusted treatment failure: RR 0.34, 95% CI 0.30 to 0.39, nine trials, 6200 participants, high quality evidence), and although PCR-adjusted treatment failure was below 5% for both ACTs, it was consistently lower with DHA-P (PCR-adjusted treatment failure: RR 0.42, 95% CI 0.29 to 0.62, nine trials, 5417 participants, high quality evidence). DHA-P has a longer prophylactic effect on new infections which may last for up to 63 days (PCR-unadjusted treatment failure: RR 0.71, 95% CI 0.65 to 0.78, two trials, 3200 participants, high quality evidence). In Asia and Oceania, no differences have been shown at day 28 (four trials, 1143 participants, moderate quality evidence), or day 63 (one trial, 323 participants, low quality evidence). Compared to artemether-lumefantrine, no difference was seen in prolonged QTc (low quality evidence), and no cardiac arrhythmias were reported. The frequency of other adverse events is probably similar with both combinations (moderate quality evidence). DHA-P versus artesunate plus mefloquine In Asia, over 28 days follow-up, DHA-P is as effective as artesunate plus mefloquine at preventing further parasitaemia (PCR-unadjusted treatment failure: eight trials, 3487 participants, high quality evidence). Once adjusted by PCR to exclude new infections, treatment failure at day 28 was below 5% for both ACTs in all eight trials, but lower with DHA-P in two trials (PCR-adjusted treatment failure: RR 0.41 95% CI 0.21 to 0.80, eight trials, 3482 participants, high quality evidence). Both combinations contain partner drugs with very long half-lives and no consistent benefit in preventing new infections has been seen over 63 days follow-up (PCR-unadjusted treatment failure: five trials, 2715 participants, moderate quality evidence). In the only trial from South America, there were fewer recurrent parastaemias over 63 days with artesunate plus mefloquine (PCR-unadjusted treatment failure: RR 6.19, 95% CI 1.40 to 27.35, one trial, 445 participants, low quality evidence), but no differences were seen once adjusted for new infections (PCR-adjusted treatment failure: one trial, 435 participants, low quality evidence). DHA-P is associated with less nausea, vomiting, dizziness, sleeplessness, and palpitations compared to artesunate plus mefloquine (moderate quality evidence). DHA-P was associated with more frequent prolongation of the QTc interval (low quality evidence), but no cardiac arrhythmias were reported. Authors' conclusions In Africa, dihydroartemisinin-piperaquine reduces overall treatment failure compared to artemether-lumefantrine, although both drugs have PCR-adjusted failure rates of less than 5%. In Asia, dihydroartemisinin-piperaquine is as effective as artesunate plus mefloquine, and is better tolerated. PLAIN LANGUAGE SUMMARY Dihydroartemisinin-piperaquine for treating uncomplicated malaria This review summarises trials evaluating the effects of dihydroartemisinin-piperaquine (DHA-P) compared to other artemisinin-based combination therapies recommended by the World Health Organization. After searching for relevant trials up to July 2013, we included 27 randomized controlled trials, enrolling 16,382 adults and children and conducted between 2002 and 2010. What is uncomplicated malaria and how might dihydroartemisinin-piperaquine work Uncomplicated malaria is the mild form of malaria which usually causes a fever, with or without headache, tiredness, muscle pains, abdominal pains, nausea, and vomiting. If left untreated, uncomplicated malaria can develop into severe malaria with kidney failure, breathing difficulties, fitting, unconsciousness, and eventually death. DHA-P is one of five artemisinin-based combination therapies the World Health Organization currently recommends to treat malaria. These combinations contain an artemisinin component (such as dihydroartemisinin) which works very quickly to clear the malaria parasite from the person's blood, and a longer acting drug (such as piperaquine) which clears the remaining parasites from the blood and may prevent new infections with malaria for several weeks. What the research says DHA-P versus artemether lumefantrine In studies of people living in Africa, both DHA-P and artemether-lumefantrine are very effective at treating malaria (high quality evidence). However, DHA-P cures slightly more patients than artemether-lumefantrine, and it also prevents further malaria infections for longer after treatment (high quality evidence). DHA-P and artemether-lumefantrine probably have similar side effects (moderate quality evidence). DHA-P versus artesunate plus mefloquine In studies of people living in Asia, DHA-P is as effective as artesunate plus mefloquine at treating malaria (moderate quality evidence). Artesunate plus mefloquine probably causes more nausea, vomiting, dizziness, sleeplessness, and palpitations than DHA-P (moderate quality evidence). Overall, in some people, DHA-P has been seen to cause short term changes in electrocardiographs tracing the conduction of the heart rhythm (low quality evidence), but these small changes on the electrocardiograph resolved within one week without serious consequences. PMID:24443033

Dronedarone: current evidence and future questions.

PubMed

Schafer, Jeremy A; Kjesbo, Nicole K; Gleason, Patrick P

2010-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting more than 2.2 million Americans. ACC/AHA/ESC guidelines for the management of patients with AF recommend amiodarone for maintaining sinus rhythm. Dronedarone is a derivative of amiodarone indicated for the treatment of AF. To provide an overview of dronedarone with a focus on the phase III trials and discuss unresolved questions of dronedarone. A literature search was conducted via the PubMed database using the keyword "dronedarone." Search was limited to human trials in english. The FDA website was searched for briefing documents and subcommittee meetings on dronedarone. Clinicaltrials.gov was searched with the keyword dronedarone for upcoming or unpublished clinical trials. Five phase III trials are available for dronedarone: ANDROMEDA, EURIDIS/ADONIS, ATHENA, ERATO, and DIONYSIS. EURIDIS/ADONIS and ATHENA demonstrated a reduction AF recurrence with dronedarone compared to placebo. The ANDROMEDA trial recruited patients with recent hospitalization for heart failure and was terminated due to an excess of deaths in the dronedarone group. The DIONYSIS trial was a comparative effectiveness trial that demonstrated less efficacy for dronedarone but improved tolerability compared to amiodarone. Dronedarone represents an option in the management of AF in select patients. Dronedarone is not appropriate in patients with recently decompensated heart failure or those treated with strong CYP3A4 inhibitors or medications prolonging the QT interval. Dronedarone appears to have improved tolerability at the expense of decreased efficacy when compared to amiodarone. Questions remain on the long-term safety, use in patients with heart failure, retreatment after dronedarone or amiodarone failure, and comparative efficacy with a rate control strategy.

Effect of cocoa products on blood pressure: systematic review and meta-analysis.

PubMed

Desch, Steffen; Schmidt, Johanna; Kobler, Daniela; Sonnabend, Melanie; Eitel, Ingo; Sareban, Mahdi; Rahimi, Kazem; Schuler, Gerhard; Thiele, Holger

2010-01-01

Cocoa products such as dark chocolate and cocoa beverages may have blood pressure (BP)-lowering properties due to their high content of plant-derived flavanols. We performed a meta-analysis of randomized controlled trials assessing the antihypertensive effects of flavanol-rich cocoa products. The primary outcome measure was the change in systolic and diastolic BP between intervention and control groups. In total, 10 randomized controlled trials comprising 297 individuals were included in the analysis. The populations studied were either healthy normotensive adults or patients with prehypertension/stage 1 hypertension. Treatment duration ranged from 2 to 18 weeks. The mean BP change in the active treatment arms across all trials was -4.5 mm Hg (95% confidence interval (CI), -5.9 to -3.2, P < 0.001) for systolic BP and -2.5 mm Hg (95% CI, -3.9 to -1.2, P < 0.001) for diastolic BP. The meta-analysis confirms the BP-lowering capacity of flavanol-rich cocoa products in a larger set of trials than previously reported. However, significant statistical heterogeneity across studies could be found, and questions such as the most appropriate dose and the long-term side effect profile warrant further investigation before cocoa products can be recommended as a treatment option in hypertension.

Analysing recurrent hospitalizations in heart failure: a review of statistical methodology, with application to CHARM-Preserved.

PubMed

Rogers, Jennifer K; Pocock, Stuart J; McMurray, John J V; Granger, Christopher B; Michelson, Eric L; Östergren, Jan; Pfeffer, Marc A; Solomon, Scott D; Swedberg, Karl; Yusuf, Salim

2014-01-01

Heart failure is characterized by recurrent hospitalizations, but often only the first event is considered in clinical trial reports. In chronic diseases, such as heart failure, analysing all events gives a more complete picture of treatment benefit. We describe methods of analysing repeat hospitalizations, and illustrate their value in one major trial. The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved study compared candesartan with placebo in 3023 patients with heart failure and preserved systolic function. The heart failure hospitalization rates were 12.5 and 8.9 per 100 patient-years in the placebo and candesartan groups, respectively. The repeat hospitalizations were analysed using the Andersen-Gill, Poisson, and negative binomial methods. Death was incorporated into analyses by treating it as an additional event. The win ratio method and a method that jointly models hospitalizations and mortality were also considered. Using repeat events gave larger treatment benefits than time to first event analysis. The negative binomial method for the composite of recurrent heart failure hospitalizations and cardiovascular death gave a rate ratio of 0.75 [95% confidence interval (CI) 0.62-0.91, P = 0.003], whereas the hazard ratio for time to first heart failure hospitalization or cardiovascular death was 0.86 (95% CI 0.74-1.00, P = 0.050). In patients with preserved EF, candesartan reduces the rate of admissions for worsening heart failure, to a greater extent than apparent from analysing only first hospitalizations. Recurrent events should be routinely incorporated into the analysis of future clinical trials in heart failure. © 2013 The Authors. European Journal of Heart Failure © 2013 European Society of Cardiology.

Securing All intraVenous devices Effectively in hospitalised patients--the SAVE trial: study protocol for a multicentre randomised controlled trial.

PubMed

Rickard, Claire M; Marsh, Nicole; Webster, Joan; Playford, E Geoffrey; McGrail, Matthew R; Larsen, Emily; Keogh, Samantha; McMillan, David; Whitty, Jennifer A; Choudhury, Md Abu; Dunster, Kimble R; Reynolds, Heather; Marshall, Andrea; Crilly, Julia; Young, Jeanine; Thom, Ogilvie; Gowardman, John; Corley, Amanda; Fraser, John F

2015-09-23

Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. 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.

Prevalence and control of high blood pressure in primary care: results from the German Metabolic and Cardiovascular Risk Study (GEMCAS).

PubMed

Balijepalli, Chakrapani; Bramlage, Peter; Lösch, Christian; Zemmrich, Claudia; Humphries, Karin H; Moebus, Susanne

2014-06-01

Contemporary epidemiological data on blood pressure readings, hypertension prevalence and control in unselected patient populations covering a broad age range are scarce. The aim here is to report the prevalence of high blood pressure and to identify factors associated with blood pressure control in a large German primary care sample. We used data from the German Metabolic and Cardiovascular Risk Study including 35 869 patients aged 18-99 years. High blood pressure was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg or using antihypertensive therapy. Factors associated with blood pressure control among patients receiving antihypertensive therapy were examined using multiple logistic regressions to estimate odds ratios and 95% confidence intervals. The prevalence of high blood pressure, uncontrolled high blood pressure and untreated high blood pressure was 54.8%, 21.3% and 17.6%, respectively. Age >50 years (1.52; 1.40-1.65), male sex (1.30; 1.20-1.41), elevated waist circumference (1.55; 1.45-1.65), high cholesterol (1.24; 1.16-1.33), high triglycerides (1.11; 1.04-1.19) and concomitant diabetes (1.29; 1.20-1.40) were independently associated with uncontrolled high blood pressure. In a majority of patients we observed hypertension despite treatment for high blood pressures. Studies examining the reasons for treatment failure are highly warranted.

Misdiagnosis of resistant hypertension: Real frequency of true resistant hypertension in patients with suspected resistance to treatment.

PubMed

Doménech, Mónica; Sastre, Enric; Camafort, Miguel; Sierra, Cristina; Coca, Antonio

2018-01-12

Resistant hypertension(RH) has been defined as failure to control office blood pressure (BP) despite the use of≥3 different antihypertensive agents at optimal doses, including, ideally, a diuretic. Apparent RH, defines patients with an incorrect diagnosis of RH due to different causes. The objective was to determine whether most patients with RH in fact have apparent but not true RH. Observational study involving 93 patients with suspected RH, being 60 patients finally included. Screening for secondary causes of hypertension was perfomed. True RH was defined as office BP>140/90mmHg despite full doses of 3 antihypertensive drugs including a diuretic. Mean age 63.7±9.8years, 68.3%were male. Office BP 154.3±14.4/84.4±13.7mmHg. Of the 60 patients, 23.3% had white coat effect, 3.3% didn't have a diuretic and 8.3% were non-adherent-to-treatment. Accordingly, 58.3% were classified as true RH. Spironolactone was added in 62.5% of patients of whom 78.4% achieved ambulatory BP control. Almost half of the patients with suspected RH were not really true RH. We provide more evidence of excess of fluid retention as an underlying cause of lack of BP control in patients with RH, reinforce the relevant paper of spironolactone for the management in those patients. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Management of hypertension in the elderly: Looking for a trade-off between cardiovascular prevention and serious adverse events.

PubMed

Buonacera, Agata; Stancanelli, Benedetta; Malatino, Lorenzo

2018-06-07

Despite the effectiveness of anti-hypertensive therapy is well recognized, the most adequate target to achieve in the management of hypertension in the elderly is still under debate. Indeed, looking at the balance between benefits and risks, accumulating evidence has recently specifically addressed this issue, focusing on controversies. Evidence surrounding a more aggressive treatment may lead to a turnaround in the clinical care of older adult hypertensives, but a balanced trade-off between benefits and risks needs to be programmed and achieved, particularly in this clinical setting. We argue whether and how the results from recent trials could influence the management of hypertension in older people.

[Psychological approaches in hypertension management].

PubMed

Abgrall-Barbry, Gaëlle; Consoli, Silla M

2006-06-01

Stress factors, especially high levels of occupational stress, are associated with hypertension. Several so-called psychological techniques have been applied to hypertension: biofeedback, relaxation techniques (Schultz' autogenic training, Jacobson's progressive relaxation), transcendental meditation, and cognitive behavioral techniques for stress management. Randomized studies show that the best results come from cognitive behavioral methods, whether or not they include relaxation techniques. Other forms of psychotherapy (such as psychoanalysis) may be useful, although their benefits for blood pressure have not been tested in controlled trials. Patients should be informed about the personal benefits they may obtain from psychological treatment. Indications are hyperreactivity to stress, high levels of occupational stress, and difficulty in tolerating or complying with antihypertensive drugs.

Evaluation and treatment of hypertensive crises in children

PubMed Central

Stein, Deborah R; Ferguson, Michael A

2016-01-01

Hypertensive crises in children are medical emergencies that must be identified, evaluated, and treated promptly and appropriately to prevent end-organ injury and even death. Treatment in the acute setting typically includes continuous intravenous antihypertensive medications with monitoring in the intensive care unit setting. Medications commonly used to treat severe hypertension have been poorly studied in children. Dosing guidelines are available, although few pediatric-specific trials have been conducted to facilitate evidence-based therapy. Regardless of what medication is used, blood pressure should be lowered gradually to allow for accommodation of autoregulatory mechanisms and to prevent cerebral ischemia. Determining the underlying cause of the blood pressure elevation may be helpful in guiding therapy. PMID:27051314

Angiotensin converting enzyme (ACE) inhibitory and antihypertensive activities of protein hydrolysate from meat of Kacang goat (Capra aegagrus hircus).

PubMed

Mirdhayati, Irdha; Hermanianto, Joko; Wijaya, Christofora H; Sajuthi, Dondin; Arihara, Keizo

2016-08-01

The meat of Kacang goat has potential for production of a protein hydrolysate. Functional ingredients from protein hydrolysate of Kacang goat meat were determined by the consistency of angiotensin-converting enzyme (ACE) inhibitory activity and antihypertensive effect. This study examined the potency of Kacang goat protein hydrolysate in ACE inhibition and antihypertensive activity. Protein hydrolysates of Kacang goat meat were prepared using sequential digestion of endo-proteinase and protease complex at several concentrations and hydrolysis times. The highest ACE inhibitory activity resulted from a hydrolysate that was digested for 4 h with 5 g kg(-1) of both enzymes. An ACE inhibitory peptide was purified and a novel peptide found with a sequence of Phe-Gln-Pro-Ser (IC50 value of 27.0 µmol L(-1) ). Both protein hydrolysates and a synthesised peptide (Phe-Gln-Pro-Ser) demonstrated potent antihypertensive activities in spontaneously hypertensive rats. Protein hydrolysate of Kacang goat meat produced by sequential digestion with endo-proteinase and protease complex has great potential as a functional ingredient, particularly as an antihypertensive agent. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Magnitude of blood pressure reduction in the placebo arms of modern hypertension trials: implications for trials of renal denervation.

PubMed

Patel, Hitesh C; Hayward, Carl; Ozdemir, Baris Ata; Rosen, Stuart D; Krum, Henry; Lyon, Alexander R; Francis, Darrel P; di Mario, Carlo

2015-02-01

Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; P<0.0001) in the nonresistant cohort and by 8.76 mm Hg (95% confidence interval, 4.83-12.70; P<0.0001) in the resistant cohort. Using metaregression, the falls were larger in trials that did not use ambulatory blood pressure monitoring as an inclusion criterion (z=2.84; P=0.0045), in those with higher baseline blood pressures (z=-0.3; P=0.0001), and in those where the patients were prescribed a continuous background of antihypertensives (z=-2.72; P=0.0065). The nontrivial magnitude of these apparent blood pressure reductions with perfectly ineffective intervention (placebo) illustrates that efficacy explorations of novel therapies for hypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design. © 2014 American Heart Association, Inc.

Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

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

Karlsson, Per, E-mail: per.karlsson@oncology.gu.se; Cole, Bernard F.; Price, Karen N.

Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. Formore » patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT.« less

New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes

PubMed Central

Senni, Michele; Paulus, Walter J.; Gavazzi, Antonello; Fraser, Alan G.; Díez, Javier; Solomon, Scott D.; Smiseth, Otto A.; Guazzi, Marco; Lam, Carolyn S. P.; Maggioni, Aldo P.; Tschöpe, Carsten; Metra, Marco; Hummel, Scott L.; Edelmann, Frank; Ambrosio, Giuseppe; Stewart Coats, Andrew J.; Filippatos, Gerasimos S.; Gheorghiade, Mihai; Anker, Stefan D.; Levy, Daniel; Pfeffer, Marc A.; Stough, Wendy Gattis; Pieske, Burkert M.

2014-01-01

The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed. PMID:25104786

[The problems of antihypertensive balneotherapy].

PubMed

Vladimirskiĭ, E V; Fil'tsagina, T N

2013-01-01

This review is devoted to the challenging problems of balneotherapeutics, such as the mechanisms of antihypertensive balneotherapy and its optimization. The experience of the authors with the practical application of chloride - sodium, iodine - bromide, and hydrogen sulfide mineral baths is analysed in comparison with the literature data. The role, dosage regimen, and duration of balneotherapeutic treatment as well as the effectiveness of its combination with medicamental therapy are considered. The authors hope that the discussion of these issues will be conducive to the solution of problems currently facing modern antihypertensive balneotherapy.

Respiratory Support in Bronchiolitis: Trial Evidence.

PubMed

Cunningham, Steve

2018-05-01

Acute viral lower respiratory tract infection is frequently associated with hypoxemia and respiratory distress, sometimes progressing to hypercarbia and respiratory failure. In recent years, trials have assessed the effects of oxygen supplementation and respiratory support with high-flow oxygen therapy. An oxygen saturation target of 90% is as safe and clinically effective as 94% in infants with bronchiolitis. Trials of high-flow humidified oxygen have demonstrated safety, but as yet poorly demarcated an appropriate place for use within the clinical course of the disease. Effective trials of continuous positive airway pressure are lacking and urgently required. The trials reported to date have highlighted the need for common outcomes in relation to treatment failure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Outcomes of a Telehealth Intervention for Homebound Older Adults with Heart or Chronic Respiratory Failure: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Gellis, Zvi D.; Kenaley, Bonnie; McGinty, Jean; Bardelli, Ellen; Davitt, Joan; Ten Have, Thomas

2012-01-01

Purpose: Telehealth care is emerging as a viable intervention model to treat complex chronic conditions, such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), and to engage older adults in self-care disease management. Design and Methods: We report on a randomized controlled trial examining the impact of a multifaceted…

The safety of sacubitril-valsartan for the treatment of chronic heart failure.

PubMed

Tyler, Jeffrey M; Teerlink, John R

2017-02-01

Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril. Areas covered: This review discusses the clinical efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril-valsartan in heart failure with reduced ejection fraction. Expert opinion: Based on the PARADIGM-HF trial, sacubitril-valsartan offers compelling reductions in meaningful clinical endpoints, independent of age or severity of disease. The rate of adverse events was comparable between the enalapril and sacubitril-valsartan groups, although the absolute rates are likely underestimated due to the entry criteria and run-in period. Future trials and post-market surveillance are critical to better understand the risk of angioedema in high risk populations, particularly African-Americans, as well as long-term theoretical risks including the potential for increased cerebral amyloid plaque deposition with possible development of neurocognitive disease. Current trials are underway to evaluate potential benefit in patients with heart failure with preserved ejection fraction.

Effects of self-management intervention on health outcomes of patients with heart failure: a systematic review of randomized controlled trials

PubMed Central

Jovicic, Aleksandra; Holroyd-Leduc, Jayna M; Straus, Sharon E

2006-01-01

Background Heart failure is the most common cause of hospitalization among adults over 65. Over 60% of patients die within 10 years of first onset of symptoms. The objective of this study is to determine the effectiveness of self-management interventions on hospital readmission rates, mortality, and health-related quality of life in patients diagnosed with heart failure. Methods The study is a systematic review of randomized controlled trials. The following data sources were used: MEDLINE (1966-11/2005), EMBASE (1980-11/2005), CINAHL (1982-11/2005), the ACP Journal Club database (to 11/2005), the Cochrane Central Trial Registry and the Cochrane Database of Systematic Reviews (to 11/2005); article reference lists; and experts in the field. We included randomized controlled trials of self-management interventions that enrolled patients 18 years of age or older who were diagnosed with heart failure. The primary outcomes of interest were all-cause hospital readmissions, hospital readmissions due to heart failure, and mortality. Secondary outcomes were compliance with treatment and quality of life scores. Three reviewers independently assessed the quality of each study and abstracted the results. For each included study, we computed the pooled odds ratios (OR) for all-cause hospital readmission, hospital readmission due to heart failure, and death. We used a fixed effects model to quantitatively synthesize results. We were not able to pool effects on health-related quality of life and measures of compliance with treatment, but we summarized the findings from the relevant studies. We also summarized the reported cost savings. Results From 671 citations that were identified, 6 randomized trials with 857 patients were included in the review. Self-management decreased all-cause hospital readmissions (OR 0.59; 95% confidence interval (CI) 0.44 to 0.80, P = 0.001) and heart failure readmissions (OR 0.44; 95% CI 0.27 to 0.71, P = 0.001). The effect on mortality was not significant (OR = 0.93; 95% CI 0.57 to 1.51, P = 0.76). Adherence to prescribed medical advice improved, but there was no significant difference in functional capabilities, symptom status and quality of life. The reported savings ranged from $1300 to $7515 per patient per year. Conclusion Self-management programs targeted for patients with heart failure decrease overall hospital readmissions and readmissions for heart failure. PMID:17081306

Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Briel, Matthias; Christ-Crain, Mirjam; Bonnema, Steen J; Connell, John; Cooper, David S; Bucher, Heiner C; Müller-Brand, Jan; Müller, Beat

2007-01-01

Objective To determine the effect of adjunctive antithyroid drugs on the risk of treatment failure, hypothyroidism, and adverse events after radioiodine treatment. Design Meta-analysis. Data sources Electronic databases (Cochrane central register of controlled trials, Medline, Embase) searched to August 2006 and contact with experts. Review methods Three reviewers independently assessed trial eligibility and quality. Pooled relative risks for treatment failure and hypothyroidism after radioiodine treatment with and without adjunctive antithyroid drugs were calculated with a random effects model. Results We identified 14 relevant randomised controlled trials with a total of 1306 participants. Adjunctive antithyroid medication was associated with an increased risk of treatment failure (relative risk 1.28, 95% confidence interval 1.07 to 1.52; P=0.006) and a reduced risk for hypothyroidism (0.68, 0.53 to 0.87; P=0.006) after radioiodine treatment. We found no difference in summary estimates for the different antithyroid drugs or for whether antithyroid drugs were given before or after radioiodine treatment. Conclusions Antithyroid drugs potentially increase rates of failure and reduce rates of hypothyroidism if they are given in the week before or after radioiodine treatment, respectively. PMID:17309884

A systematic review of discontinued trials suggested that most reasons for recruitment failure were preventable.

PubMed

Briel, Matthias; Olu, Kelechi Kalu; von Elm, Erik; Kasenda, Benjamin; Alturki, Reem; Agarwal, Arnav; Bhatnagar, Neera; Schandelmaier, Stefan

2016-12-01

To collect and classify reported reasons for recruitment failure in discontinued randomized controlled trials (RCTs) and to assess reporting quality. We systematically searched MEDLINE and EMBASE (2010-2014) and a previous cohort of RCTs for published RCTs reporting trial discontinuation due to poor recruitment. Teams of two investigators selected eligible RCTs working independently and extracted information using standardized forms. We used an iterative approach to classify reasons for poor recruitment. We included 172 RCTs discontinued due to poor recruitment (including 26 conference abstracts and 63 industry-funded RCTs). Of those, 131 (76%) reported one or more reasons for discontinuation due to poor recruitment. We identified 28 different reasons for recruitment failure; most frequently mentioned were overestimation of prevalence of eligible participants and prejudiced views of recruiters and participants on trial interventions. Few RCTs reported relevant details about the recruitment process such as how eligible participants were identified, the number of patients assessed for eligibility, and who actually recruited participants. Our classification could serve as a checklist to assist investigators in the planning of RCTs. Most reasons for recruitment failure seem preventable with a pilot study that applies the planned informed consent procedure. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessing the Effects of Non-steroidal Anti-inflammatory Drugs on Antihypertensive Drug Therapy Using Post-Marketing Surveillance Database

PubMed Central

Ishiguro, Chieko; Fujita, Toshiharu; Omori, Takashi; Fujii, Yosuke; Mayama, Takeshi; Sato, Tosiya

2008-01-01

Background Antihypertensive and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat many common diseases. However, it has been suspected that interactions between these drugs exist. Here, we assessed the interactions between non-selective NSAIDs and several classes of antihypertensive drugs. Methods The study design was a cohort study using “The Antihypertensive Drug Database,” which is a collection of data accumulated from Drug Use Investigations. Subjects newly starting antihypertensive drug therapy were identified in the database. We compared the “User” group, who were co-administered NSAIDs, with the “Non-user” group, who were not. The outcome measure was the change in systolic blood pressure from the baseline after 2 months of treatment. We estimated the non-adjusted and adjusted differences in the change in systolic blood pressure between the “User” and “Non-user” groups. Results Data were collected for a total of 1,204 subjects, of whom 364 were prescribed beta blockers, 60 were prescribed diuretics, 628 were prescribed angiotensin-converting enzyme inhibitors, and 152 were prescribed calcium channel blockers. The adjusted difference in the change in systolic blood pressure between the User (n = 301) and Non-user (n = 903) groups was 2.88 mmHg (95% confidence interval: 0.89, 4.87); thus, systolic blood pressure in the Non-User group decreased further from the baseline than that in the User group. In subjects administered beta blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers, the corresponding differences were 0.37 mmHg (-3.24, 3.98), 6.11 mmHg (-3.16, 15.37), 3.85 mmHg (1.16, 6.66), and 3.50 mmHg (-2.03, 9.02). Conclusion The effectiveness of antihypertensive drugs was attenuated by the co-administration of NSAIDs. The differences in the effects of NSAIDs varied with different classes of antihypertensive drugs. PMID:18469490

Discovery of Anti-Hypertensive Oligopeptides from Adlay Based on In Silico Proteolysis and Virtual Screening

PubMed Central

Qiao, Liansheng; Li, Bin; Chen, Yankun; Li, Lingling; Chen, Xi; Wang, Lingzhi; Lu, Fang; Luo, Ganggang; Li, Gongyu; Zhang, Yanling

2016-01-01

Adlay (Coix larchryma-jobi L.) was the commonly used Traditional Chinese Medicine (TCM) with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopeptides from adlay were not clear. To discover the definite anti-hypertensive oligopeptides from adlay, in silico proteolysis and virtual screening were implemented to obtain potential oligopeptides, which were further identified by biochemistry assay and molecular dynamics simulation. In this paper, ten sequences of adlay prolamins were collected and in silico hydrolyzed to construct the oligopeptide library with 134 oligopeptides. This library was reverse screened by anti-hypertensive pharmacophore database, which was constructed by our research team and contained ten anti-hypertensive targets. Angiotensin-I converting enzyme (ACE) was identified as the main potential target for the anti-hypertensive activity of adlay oligopeptides. Three crystal structures of ACE were utilized for docking studies and 19 oligopeptides were finally identified with potential ACE inhibitory activity. According to mapping features and evaluation indexes of pharmacophore and docking, three oligopeptides were selected for biochemistry assay. An oligopeptide sequence, NPATY (IC50 = 61.88 ± 2.77 µM), was identified as the ACE inhibitor by reverse-phase high performance liquid chromatography (RP-HPLC) assay. Molecular dynamics simulation of NPATY was further utilized to analyze interactive bonds and key residues. ALA354 was identified as a key residue of ACE inhibitors. Hydrophobic effect of VAL518 and electrostatic effects of HIS383, HIS387, HIS513 and Zn2+ were also regarded as playing a key role in inhibiting ACE activities. This study provides a research strategy to explore the pharmacological mechanism of Traditional Chinese Medicine (TCM) proteins based on in silico proteolysis and virtual screening, which could be beneficial to reveal the pharmacological action of TCM proteins and provide new lead compounds for peptides-based drug design. PMID:27983650

Do advertisements for antihypertensive drugs in Australia promote quality prescribing? A cross-sectional study.

PubMed

Montgomery, Brett D; Mansfield, Peter R; Spurling, Geoffrey K; Ward, Alison M

2008-05-20

Antihypertensive medications are widely prescribed by doctors and heavily promoted by the pharmaceutical industry. Despite strong evidence of the effectiveness and cost-effectiveness of thiazide diuretics, trends in both promotion and prescription of antihypertensive drugs favour newer, less cost-effective agents. Observational evidence shows correlations between exposure to pharmaceutical promotion and less ideal prescribing. Our study therefore aimed to determine whether print advertisements for antihypertensive medications promote quality prescribing in hypertension. We performed a cross-sectional study of 113 advertisements for antihypertensive drugs from 4 general practice-oriented Australian medical publications in 2004. Advertisements were evaluated using a quality checklist based on a review of hypertension management guidelines. Main outcome measures included: frequency with which antihypertensive classes were advertised, promotion of thiazide class drugs as first line agents, use of statistical claims in advertisements, mention of harms and prices in the advertisements, promotion of assessment and treatment of cardiovascular risk, promotion of lifestyle modification, and targeting of particular patient subgroups. Thiazides were the most frequently advertised drug class (48.7% of advertisements), but were largely promoted in combination preparations. The only thiazide advertised as a single agent was the most expensive, indapamide. No advertisement specifically promoted any thiazide as a better first-line drug. Statistics in the advertisements tended to be expressed in relative rather than absolute terms. Drug costs were often reported, but without cost comparisons between drugs. Adverse effects were usually reported but largely confined to the advertisements' small print. Other than mentioning drug interactions with alcohol and salt, no advertisements promoted lifestyle modification. Few advertisements (2.7%) promoted the assessment of cardiovascular risk. Print advertisements for antihypertensive medications in Australia provide some, but not all, of the key messages required for guideline-concordant care. These results have implications for the regulation of drug advertising and the continuing education of doctors.

Assessing the effects of non-steroidal anti-inflammatory drugs on antihypertensive drug therapy using post-marketing surveillance database.

PubMed

Ishiguro, Chieko; Fujita, Toshiharu; Omori, Takashi; Fujii, Yosuke; Mayama, Takeshi; Sato, Tosiya

2008-01-01

Antihypertensive and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat many common diseases. However, it has been suspected that interactions between these drugs exist. Here, we assessed the interactions between non-selective NSAIDs and several classes of antihypertensive drugs. The study design was a cohort study using "The Antihypertensive Drug Database," which is a collection of data accumulated from Drug Use Investigations. Subjects newly starting antihypertensive drug therapy were identified in the database. We compared the "User" group, who were co-administered NSAIDs, with the "Non-user" group, who were not. The outcome measure was the change in systolic blood pressure from the baseline after 2 months of treatment. We estimated the non-adjusted and adjusted differences in the change in systolic blood pressure between the "User" and "Non-user" groups. Data were collected for a total of 1,204 subjects, of whom 364 were prescribed beta blockers, 60 were prescribed diuretics, 628 were prescribed angiotensin-converting enzyme inhibitors, and 152 were prescribed calcium channel blockers. The adjusted difference in the change in systolic blood pressure between the User (n = 301) and Non-user (n = 903) groups was 2.88 mmHg (95% confidence interval: 0.89, 4.87); thus, systolic blood pressure in the Non-User group decreased further from the baseline than that in the User group. In subjects administered beta blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers, the corresponding differences were 0.37 mmHg (-3.24, 3.98), 6.11 mmHg (-3.16, 15.37), 3.85 mmHg (1.16, 6.66), and 3.50 mmHg (-2.03, 9.02). The effectiveness of antihypertensive drugs was attenuated by the co-administration of NSAIDs. The differences in the effects of NSAIDs varied with different classes of antihypertensive drugs.

Bioabsorbable versus metallic interference screws for graft fixation in anterior cruciate ligament reconstruction.

PubMed

Debieux, Pedro; Franciozi, Carlos E S; Lenza, Mário; Tamaoki, Marcel Jun; Magnussen, Robert A; Faloppa, Flávio; Belloti, João Carlos

2016-07-24

Anterior cruciate ligament (ACL) tears are frequently treated with surgical reconstruction with grafts, frequently patella tendon or hamstrings. Interference screws are often used to secure the graft in bone tunnels in the femur and tibia. This review examines whether bioabsorbable interference screws give better results than metal interference screws when used for graft fixation in ACL reconstruction. To assess the effects (benefits and harms) of bioabsorbable versus metallic interference screws for graft fixation in ACL reconstruction. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, CENTRAL (the Cochrane Library), MEDLINE, Embase, LILACS, trial registers and reference lists of articles. Date of search: January 2016. We included randomised controlled trials and quasi-randomised trials comparing bioabsorbable with metallic interferences screws in ACL reconstruction. The main outcomes sought were subjective-rated knee function, failure of treatment, and activity level. At least two review authors selected eligible trials, independently assessed risk of bias, and cross-checked data. Data were pooled whenever relevant and possible. Requests for further information were sent to the original study authors. We included 12 trials (11 randomised and one quasi-randomised) involving a total of 944 participants, and reporting follow-up results for 774. Participants in the 12 trials underwent ACL reconstruction with either hamstring tendon grafts (five trials) or patellar tendon grafts (seven trials). Trials participants were randomly allocated to bioabsorbable or metallic interference screws for graft fixation in both femur and tibia (seven trials); femur only (three trials); tibia only (one trial); location was not reported in the remaining trial. A variety of materials was used for the bioabsorbable screws, Poly-L-lactic acid (PLLA) being the most common. The metallic screws, where reported, were titanium.All trials were at high risk of bias, which invariably included performance bias. Seven trials were at high risk of attrition bias and eight at high risk of reporting bias. The quasi-randomised trial was assessed as being at high risk for selection bias. Based on these study limitations and insufficiency of the available data, we judged the quality of evidence for all outcomes was very low.The majority of the available data for patient-reported knee function was presented as Lysholm scores (0 to 100; higher scores = better function). There was very low quality but consistent evidence of no clinically important differences between the two groups in Lysholm scores at 12 months follow-up (mean difference (MD) -0.08, 95% confidence interval (CI) -1.48 to 1.32; three trials, 168 participants); 24 months (MD 0.35, 95% CI -1.27 to 1.98; three trials, 113 participants) or five or more years follow-up (MD 1.23, 95% CI -2.00 to 4.47; two trials, 71 participants). This lack of between-group differences was also reported for Lysholm scores in several trials that did not provide sufficient data for pooling as well as for other self-reported knee function scores reported in several trials.Treatment failure was represented by the summed data for implant breakage during surgery and major postoperative complications (implant failure, graft rupture, symptomatic foreign body reactions, effusion and treated arthrofibrosis and related conditions) that were usually described in the trial reports as requiring further substantive treatment. There is very low-quality evidence of greater treatment failure in the bioabsorbable screw group (60/451 versus 29/434; risk ratio (RR) 1.94 favouring metallic screw fixation, 95% CI 1.29 to 2.93; 885 participants, 11 studies). In a population with an assumed risk (based on the median control group risk) of 56 participants per 1000 having treatment failure after metallic screw fixation, this equates to 53 more (95% CI 17 to 108 more) per 1000 participants having treatment failure after bioabsorbable screw fixation. All 16 intraoperative complications in the bioabsorbable screw group were implant breakages upon screw insertion. Treatment failure defined as postoperative complications only still favoured the metallic screw group but the 95% CI also included the potential for a greater risk of treatment failure after metallic screw fixation: 44/451 versus 29/434; RR 1.44, 95% CI 0.93 to 2.23. Based on the assumed risk of 56 participants per 1000 having postoperative treatment failure after metallic screw fixation, this equates to 25 more (95% CI 4 fewer and 69 more) per 1000 participants having this outcome after bioabsorbable screw fixation.There was very low-quality evidence of very similar activity levels in the two groups at 12 and 24 months follow-up measured via the Tegner score (0 to 10; higher scores = greater activity): 12 months (MD 0.08, 95% CI -0.39 to 0.55; 122 participants, two studies); 24 months (MD 0.01, 95% CI -0.54 to 0.57; 72 participants, two studies). There is very low-quality evidence of no difference in self-reported knee function and levels of activity between bioabsorbable and metallic interference screws for graft fixation in ACL reconstruction. There is very low-quality evidence that bioabsorbable screws may be associated with more overall treatment failures, including implant breakage during surgery. Further research does not appear to be a priority, but if undertaken, should also examine costs.

Comparative Review of the Treatment Methodologies of Carotid Stenosis

PubMed Central

Bae, Coney; Szuchmacher, Mauricio; Chang, John B.

2015-01-01

The treatment of carotid stenosis entails three methodologies, namely, medical management, carotid angioplasty and stenting (CAS), as well as carotid endarterectomy (CEA). The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) have shown that symptomatic carotid stenosis greater than 70% is best treated with CEA. In asymptomatic patients with carotid stenosis greater than 60%, CEA was more beneficial than treatment with aspirin alone according to the Asymptomatic Carotid Atherosclerosis (ACAS) and Asymptomatic Carotid Stenosis Trial (ACST) trials. When CAS is compared with CEA, the CREST resulted in similar rates of ipsilateral stroke and death rates regardless of symptoms. However, CAS not only increased adverse effects in women, it also amplified stroke rates and death in elderly patients compared with CEA. CAS can maximize its utility in treating focal restenosis after CEA and patients with overwhelming cardiac risk or prior neck irradiation. When performing CEA, using a patch was equated to a more durable result than primary closure, whereas eversion technique is a new methodology deserving a spotlight. Comparing the three major treatment strategies of carotid stenosis has intrinsic drawbacks, as most trials are outdated and they vary in their premises, definitions, and study designs. With the newly codified best medical management including antiplatelet therapies with aspirin and clopidogrel, statin, antihypertensive agents, strict diabetes control, smoking cessation, and life style change, the current trials may demonstrate that asymptomatic carotid stenosis is best treated with best medical therapy. The ongoing trials will illuminate and reshape the treatment paradigm for symptomatic and asymptomatic carotid stenosis. PMID:26417191

Isolated Systolic Hypertension: An Update After SPRINT.

PubMed

Bavishi, Chirag; Goel, Sangita; Messerli, Franz H

2016-12-01

Isolated systolic hypertension is the most common hemodynamic form of hypertension in the elderly. With a rapidly aging population, the prevalence of hypertension, particularly isolated systolic hypertension, is expected to increase substantially. This phenomenon of increasing systolic pressure in the elderly is believed to be secondary to pathophysiological changes of aging as well as modifiable risk factors. Isolated systolic hypertension is associated with substantial mortality and morbidity, particularly of cerebrovascular disease. It is a rapidly growing public health concern and its management continues to remain a challenge to practicing physicians. Recent studies like the Systolic Blood Pressure Intervention Trial (SPRINT) and Heart Outcomes Prevention Evaluation (HOPE)-3 have implications for antihypertensive therapy in general and for the management of isolated systolic hypertension in particular. In this article we will review: 1) epidemiology and pathophysiologic mechanisms, 2) impact of isolated systolic hypertension on cardiovascular outcomes, 3) optimal management strategies, and 4) systolic blood pressure goals in the light of SPRINT and HOPE 3 trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Hibiscus sabdariffa L. - a phytochemical and pharmacological review.

PubMed

Da-Costa-Rocha, Inês; Bonnlaender, Bernd; Sievers, Hartwig; Pischel, Ivo; Heinrich, Michael

2014-12-15

Hibiscus sabdariffa L. (Hs, roselle; Malvaceae) has been used traditionally as a food, in herbal drinks, in hot and cold beverages, as a flavouring agent in the food industry and as a herbal medicine. In vitro and in vivo studies as well as some clinical trials provide some evidence mostly for phytochemically poorly characterised Hs extracts. Extracts showed antibacterial, anti-oxidant, nephro- and hepato-protective, renal/diuretic effect, effects on lipid metabolism (anti-cholesterol), anti-diabetic and anti-hypertensive effects among others. This might be linked to strong antioxidant activities, inhibition of α-glucosidase and α-amylase, inhibition of angiotensin-converting enzymes (ACE), and direct vaso-relaxant effect or calcium channel modulation. Phenolic acids (esp. protocatechuic acid), organic acid (hydroxycitric acid and hibiscus acid) and anthocyanins (delphinidin-3-sambubioside and cyanidin-3-sambubioside) are likely to contribute to the reported effects. More well designed controlled clinical trials are needed which use phytochemically characterised preparations. Hs has an excellent safety and tolerability record. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Obesity-Associated Hypertension: the Upcoming Phenotype in African-American Women.

PubMed

Samson, Rohan; Qi, Andrea; Jaiswal, Abhishek; Le Jemtel, Thierry H; Oparil, Suzanne

2017-05-01

The present obesity epidemic particularly affects African-American women. Whether the obesity epidemic will alter the hypertension phenotype in African-American women is entertained. The prevalence of morbid obesity is steadily increasing in African-American women, who are prone to developing hypertension (HTN) even in the absence of obesity. The obesity-associated hypertension phenotype is characterized by marked sympathetic nervous system activation and resistance/refractoriness to antihypertensive therapy. Weight loss achieved through lifestyle interventions and pharmacotherapy has a modest and rarely sustained antihypertensive effect. In contrast, bariatric surgery has a sustained antihypertensive effect, as evidenced by normalization of hypertension or lessening of antihypertensive therapy. The prevalence of HTN and its obesity-associated phenotype is likely to increase in African-American women over the next decades. Obese African-American women may be increasingly referred for bariatric surgery when hypertension remains uncontrolled despite lifestyle interventions and pharmacological therapy for weight loss and blood pressure (BP) control.

Antioxidative and antihypertensive activities of pig meat before and after cooking and in vitro gastrointestinal digestion: Comparison between Italian autochthonous pig Suino Nero Lucano and a modern crossbred pig.

PubMed

Simonetti, Amalia; Gambacorta, Emilio; Perna, Annamaria

2016-12-01

The aim of this study was to evaluate and compare antioxidative and antihypertensive activities of Longissimus dorsi muscle from Suino Nero Lucano (SNL) and a modern crossbred (CG) pigs, before and after cooking and in vitro gastrointestinal digestion. Pig meat showed antioxidative and antihypertensive activities, heat treatment decreased the thiols content but at the same time increased angiotensin I-converting enzyme (ACE) inhibitory activity, and in vitro gastrointestinal digestion enhanced the biological activity of meat. Autochthonous SNL meat showed a higher nutraceutical quality compared to CG meat, highlighting a greater potential beneficial physiological effect on human health. The results of this study indicate that the pig meat, in particular autochthonous pig meat, may be considered a functional food since it is a good source of antioxidative and antihypertensive peptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effectiveness of the selective aldosterone blocker, eplerenone, in patients with resistant hypertension.

PubMed

Calhoun, David A; White, William B

2008-01-01

Resistant hypertension is defined as uncontrolled hypertension despite intensive treatment with at least three antihypertensive agents, one of which ideally should be a diuretic. To determine the efficacy and safety of the selective aldosterone antagonist eplerenone in this population, we studied patients with resistant hypertension (clinic blood pressure [BP] >140 mm Hg systolic or >90 mm Hg diastolic on maximal doses of more than three antihypertensive agents, including a loop or thiazide diuretic). At baseline and after 12 weeks of eplerenone therapy (50 to 100 mg daily titrated to effect), patients underwent clinic and 24-hour BP measurements, serum potassium, plasma renin activity, and serum aldosterone measurements. Patients (n = 52) completing the trial averaged 62 +/- 10 years of age, were overweight (mean body mass index, 32.1 +/- 5.5 kg/m(2)), and had variable renal function (glomerular filtration rate, 106 +/- 38 mL/minute); 70% were men and 74% were non-Black. The mean number of antihypertensive agents at baseline was 3.7 +/- 0.8 (range, three to seven drugs) to achieve a clinic BP of 150.5/84.1 mm Hg. The mean serum aldosterone was 12.9 +/- 7.6 ng/mL and plasma renin activity was 2.3 +/- 2.7 ng/mL/hour. After eplerenone, the change from baseline in the clinic BP was -17.6/-7.9 mm Hg (P < .0001 for both systolic blood pressure [SBP] and diastolic blood pressure [DBP]) and in 24-hour BP was -12.2/-6.0 mm Hg (P < .0001 for both). The number of antihypertensive drugs decreased to 3.3 +/- 0.9 (range, one to seven agents). Plasma potassium increased by 0.30 +/- 0.45 mEq/L (P < .001), but there were only three instances in two patients of mild hyperkalemia (potassium >5.5 mEq/L, but <6.0 mEq/L), despite all patients being on a background therapy that included an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Reductions in clinic and ambulatory BP were related to baseline clinic and ambulatory BP values (r(2) > 0.3 for both SBP and DBP, P < .0001), weakly related to baseline serum aldosterone (r = -0.30; P = .05), and unrelated to plasma renin activity, age, gender, or race. In conclusion, eplerenone demonstrated substantial efficacy in treatment-resistant hypertension and was well-tolerated with modest changes in plasma potassium. Serum aldosterone and plasma renin activity did not predict BP responses to eplerenone in this population.

Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl.

PubMed

Chin, Melanie P; Wrolstad, Danielle; Bakris, George L; Chertow, Glenn M; de Zeeuw, Dick; Goldsberry, Angie; Linde, Peter G; McCullough, Peter A; McMurray, John J; Wittes, Janet; Meyer, Colin J

2014-12-01

A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2-related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention. We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min(-1) 1.73 m(-2)) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl- and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events. Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Evolution of Biomarker Guided Therapy for Heart Failure: Current Concepts and Trial Evidence

PubMed Central

Pruett, Amanda E; Lee, Amanda K; Patterson, Herbert; Schwartz, Todd A; Glotzer, Jana M; Adams, Jr, Kirkwood F

2015-01-01

Optimizing management of patients with heart failure remains quite challenging despite many significant advances in drug and device therapy for this syndrome. Although a large body of evidence from robust clinical trials supports multiple thera-pies, utilization of these well-established treatments remains inconsistent and outcomes suboptimal in “real-world” patients with heart failure. Disease management programs may be effective, but are difficult to implement due to cost and logistical issues. Another approach to optimizing therapy is to utilize biomarkers to guide therapeutic choices. Natriuretic peptides pro-vide additional information of significant clinical value in the diagnosis and estimation of risk inpatients with heart failure. Ongoing research suggests a potential important added role for natriuretic peptides in heart failure. Guiding therapy based on serial changes in these biomarkers may be an effective strategy to optimize treatment and achieve better outcomes in this syn-drome. Initial, innovative, proof-of-concept studies have provided encouraging results and important insights into key as-pects of this strategy, but well designed, large-scale, multicenter, randomized, outcome trials are needed to definitively estab-lish this novel approach to management. Given the immense and growing public health burden of heart failure, identification of cost-effective ways to decrease the morbidity and mortality due to this syndrome is critical. PMID:24251462

The role of the angiotensin II type I receptor blocker telmisartan in the treatment of non-alcoholic fatty liver disease: a brief review.

PubMed

Borém, Luciana M A; Neto, João F R; Brandi, Igor V; Lelis, Deborah F; Santos, Sergio H S

2018-04-10

Non-alcoholic fatty liver disease (NAFLD) is currently considered an important component of metabolic syndrome (MetS). The spectrum of NAFLD includes conditions that range from simple hepatic steatosis to non-alcoholic steatohepatitis. NAFLD is correlated with liver-related death and is predicted to be the most frequent indication for liver transplantation by 2030. Insulin resistance is directly correlated to the central mechanisms of hepatic steatosis in NAFLD patients, which is strongly correlated to the imbalance of the renin-angiotensin system, that is involved in lipid and glucose metabolism. Among the emerging treatment approaches for NAFLD is the anti-hypertensive agent telmisartan, which has positive effects on liver, lipid, and glucose metabolism, especially through its action on the renin-angiotensin system, by blocking the ACE/AngII/AT1 axis and increasing ACE2/Ang(1-7)/Mas axis activation. However, treatment with this drug is only recommended for patients with an established indication for anti-hypertensive therapy. Thus, there is an increased need for large randomized controlled trials with the aim of elucidating the effects of telmisartan on liver disease, especially NAFLD. From this perspective, the present review aims to provide a brief examination of the pathogenesis of NAFLD/NASH and the role of telmisartan on preventing liver disorders and thus to improve the discussion on potential therapies.

Best antihypertensive strategies to improve blood pressure control in Latin America: position of the Latin American Society of Hypertension.

PubMed

Coca, Antonio; López-Jaramillo, Patricio; Thomopoulos, Costas; Zanchetti, Alberto

2018-02-01

: Evidence from randomized trials has shown that effective treatment with blood pressure (BP)-lowering medications reduces the risk of cardiovascular morbidity and mortality in patients with hypertension. Therefore, hypertension control and prevention of subsequent morbidity and mortality should be achievable for all patients worldwide. However, many people in Latin America remain undiagnosed, untreated or have inadequately controlled BP, even where this is access to health systems. Barriers to hypertension control in low-income countries include difficulties in transportation to health services; inappropriate opening hours; difficulties in making clinic appointments; inaccessible healthcare facilities, lack of insurance and high treatment costs. After a review of the best recent available evidence on the efficacy and tolerability of antihypertensive drugs and strategies, the Latin American Society of Hypertension experts conclude that all major classes of BP-lowering drugs be available to hypertensive patients, because all have been shown to reduce major cardiovascular outcomes compared with placebo, and have shown to be associated with a comparable risk of major cardiovascular events and mortality when compared between classes. Within each class, no evidence whatsoever is available to show that one compound is more effective than another in outcome prevention. Therefore, the selection of individual drugs may be based mainly on the capacity of Latin American governments to obtain the lowest prices of the different molecules manufactured by companies with high production quality standards.

Reducing failures of working memory with performance feedback.

PubMed

Adam, Kirsten C S; Vogel, Edward K

2016-10-01

Fluctuations in attentional control can lead to failures of working memory (WM), in which the subject is no better than chance at reporting items from a recent display. In three experiments, we used a whole-report measure of visual WM to examine the impact of feedback on the rate of failures. In each experiment, subjects remembered an array of colored items across a blank delay, and then reported the identity of items using a whole-report procedure. In Experiment 1, we gave subjects simple feedback about the number of items they correctly identified at the end of each trial. In Experiment 2, we gave subjects additional information about the cumulative number of items correctly identified within each block. Finally, in Experiment 3, we gave subjects weighted feedback in which poor trials resulted in lost points and consistent successful performance received "streak" points. Surprisingly, simple feedback (Exp. 1) was ineffective at improving average performance or decreasing the rate of poor-performance trials. Simple cumulative feedback (Exp. 2) modestly decreased poor-performance trials (by 7 %). Weighted feedback produced the greatest benefits, decreasing the frequency of poor-performance trials by 28 % relative to baseline performance. This set of results demonstrates the usefulness of whole-report WM measures for investigating the effects of feedback on WM performance. Further, we showed that only a feedback structure that specifically discouraged lapses using negative feedback led to large reductions in WM failures.

Effect of a preoperative self-catheterization video on anxiety: a randomized controlled trial.

PubMed

Oliphant, Sallie S; Lowder, Jerry L; Ghetti, Chiara; Zyczynski, Halina M

2013-03-01

The purpose of this study was to determine if a clean intermittent self-catheterization (CISC) instructional video could improve anxiety in women undergoing prolapse and/or incontinence surgery. A total of 199 women were randomized to preoperative CISC video or routine counseling prior to prolapse/incontinence surgery. Patient anxiety, satisfaction, and concerns about CISC were evaluated using the State-Trait Anxiety Inventory-State (STAI-S) and study-specific visual analog scale (VAS) questions at four perioperative time points. STAI-S and VAS anxiety measures were similar at baseline between groups; no significant differences were seen by group at any time point. STAI-S scores varied considerably over time, with highest scores at voiding trial failure and lowest scores at postoperative visit. Women in the video group had improved STAI-S scores and reported less worry and more comfort with CISC immediately following video viewing. Women with anxiety/depression had higher STAI-S scores at voiding trial failure and discharge and reported less anxiety reduction following video viewing compared to non-anxious/non-depressed peers. Women undergoing prolapse/incontinence surgery have significant perioperative anxiety, which is exacerbated by voiding trial failure. Preoperative CISC video viewing decreases anxiety scores immediately following viewing, but this effect is not sustained at voiding trial failure. Women with baseline anxiety/depression exhibit less anxiety score improvement after video viewing and have overall higher anxiety scores perioperatively.

Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

PubMed Central

Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma

2018-01-01

Background Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. Methods We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. Results We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. Conclusion The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. PMID:28780577

Blood pressure control for diabetic retinopathy

PubMed Central

Do, Diana V; Wang, Xue; Vedula, Satyanarayana S; Marrone, Michael; Sleilati, Gina; Hawkins, Barbara S; Frank, Robert N

2015-01-01

Background Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Simultaneous blood pressure control has been advocated for the same purpose, but findings reported from individual studies have supported varying conclusions regarding the ocular benefit of interventions on blood pressure. Objectives The primary aim of this review was to summarize the existing evidence regarding the effect of interventions to control or reduce blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. A secondary aim was to compare classes of anti-hypertensive medications with respect to the same outcomes. Search methods We searched a number of electronic databases including CENTRAL as well as ongoing trial registries. We last searched the electronic databases on 25 April 2014. We also reviewed reference lists of review articles and trial reports selected for inclusion. In addition, we contacted investigators of trials with potentially pertinent data. Selection criteria We included in this review randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to intense versus less intense blood pressure control, to blood pressure control versus usual care or no intervention on blood pressure, or to different classes of anti-hypertensive agents versus placebo. Data collection and analysis Pairs of review authors independently reviewed titles and abstracts from electronic and manual searches and the full text of any document that appeared to be relevant. We assessed included trials independently for risk of bias with respect to outcomes reported in this review. We extracted data regarding trial characteristics, incidence and progression of retinopathy, visual acuity, quality of life, and cost-effectiveness at annual intervals after study entry whenever provided in published reports and other documents available from included trials. Main results We included 15 RCTs, conducted primarily in North America and Europe, that had enrolled 4157 type 1 and 9512 type 2 diabetic participants, ranging from 16 to 2130 participants in individual trials. In 10 of the 15 RCTs, one group of participants was assigned to one or more anti-hypertensive agents and the control group received placebo. In three trials, intense blood pressure control was compared to less intense blood pressure control. In the remaining two trials, blood pressure control was compared with usual care. Five of the 15 trials enrolled type 1 diabetics, and 10 trials enrolled type 2 diabetics. Six trials were sponsored entirely by pharmaceutical companies, seven trials received partial support from pharmaceutical companies, and two studies received support from government-sponsored grants and institutional support. Study designs, populations, interventions, and lengths of follow-up (range one to nine years) varied among the included trials. Overall, the quality of the evidence for individual outcomes was low to moderate. For the primary outcomes, incidence and progression of retinopathy, the quality of evidence was downgraded due to inconsistency and imprecision of estimates from individual studies and differing characteristics of participants. For primary outcomes among type 1 diabetics, one of the five trials reported incidence of retinopathy and one trial reported progression of retinopathy after 4 to 5 years of treatment and follow-up; four of the five trials reported a combined outcome of incidence and progression over the same time interval. Among type 2 diabetics, 5 of the 10 trials reported incidence of diabetic retinopathy and 3 trials reported progression of retinopathy; one of the 10 trials reported a combined outcome of incidence and progression during a 4-to 5-year follow-up period. One trial in which type 2 diabetics participated had reported no primary (or secondary) outcome targeted for this review. The evidence from these trials supported a benefit of more intensive blood pressure control intervention with respect to 4- to 5-year incidence of diabetic retinopathy (estimated risk ratio (RR) 0.80; 95% confidence interval (CI) 0.71 to 0.92) and the combined outcome of incidence and progression (estimated RR 0.78; 95% CI 0.63 to 0.97). The available evidence provided less support for a benefit with respect to 4- to 5-year progression of diabetic retinopathy (point estimate was closer to 1 than point estimates for incidence and combined incidence and progression, and the CI overlapped 1; estimated RR 0.88; 95% CI 0.73 to 1.05). The available evidence regarding progression to proliferative diabetic retinopathy or clinically significant macular edema or moderate to severe loss of best-corrected visual acuity did not support a benefit of intervention on blood pressure: estimated RRs and 95% CIs 0.95 (0.83 to 1.09) and 1.06 (0.85 to 1.33), respectively, after 4 to 5 years of follow-up. Findings within subgroups of trial participants (type 1 and type 2 diabetics; participants with normal blood pressure levels at baseline and those with elevated levels) were similar to overall findings. The adverse event reported most often (7 of 15 trials) was death, yielding an estimated RR 0.86 (95% CI 0.64 to 1.14). Hypotension was reported from three trials; the estimated RR was 2.08 (95% CI 1.68 to 2.57). Other adverse ocular events were reported from single trials. Authors’ conclusions Hypertension is a well-known risk factor for several chronic conditions in which lowering blood pressure has proven to be beneficial. The available evidence supports a beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to 4 to 5 years. However, the lack of evidence to support such intervention to slow progression of diabetic retinopathy or to prevent other outcomes considered in this review, along with the relatively modest support for the beneficial effect on incidence, weakens the conclusion regarding an overall benefit of intervening on blood pressure solely to prevent diabetic retinopathy. PMID:25637717

External cephalic version facilitation for breech presentation at term.

PubMed

Hofmeyr, G J

2001-01-01

Tocolytic drugs to relax the uterus as well as other methods have been also used in an attempt to facilitate external cephalic version at term. The objective of this review is to assess the effects of routine tocolysis, fetal acoustic stimulation, epidural or spinal analgesia and transabdominal amnioinfusion for external cephalic version at term on successful version and measures of pregnancy outcome. The Cochrane Pregnancy and Childbirth Group Trials Register and the Cochrane Controlled Trials Register were searched. Date of last search: April 2001. Randomised and quasi-randomised trials comparing routine versus selective tocolysis; fetal acoustic stimulation in midline fetal spine positions versus dummy or no stimulation; epidural or spinal analgesia versus no regional analgesia; or transabdominal amnioinfusion versus no amnioinfusion for external cephalic version at term. Eligibility and trial quality were assessed by the reviewer. In seven trials, routine tocolysis was associated with fewer failures of external cephalic version (relative risk 0.74, 95% confidence interval 0.64 to 0.87). There were no significant differences between non-cephalic presentations at birth. Caesarean sections were reduced (relative risk 0.85, confidence interval 0.72-0.99). Fetal acoustic stimulation in midline fetal spine positions was associated with fewer failures of external cephalic version at term (relative risk 0.17, 95% confidence interval 0.05 to 0.60). With epidural or spinal analgesia, external cephalic version failure, non-cephalic births and caesarean sections were reduced in one trial but not the other. The overall differences were not statistically significant. No randomised trials of transabdominal amnioinfusion for external cephalic version at term were located. Routine tocolysis appears to reduce the failure rate of external cephalic version at term. Although promising, there is not enough evidence to evaluate the use of fetal acoustic stimulation in midline fetal spine positions, nor of epidural or spinal analgesia. Large volume intravenous preloading may have contributed to the effectiveness demonstrated in one of the latter trials. No randomised trials of transabdominal amnioinfusion for external cephalic version at term were found.

Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials.

PubMed

Danchin, Nicolas; Cucherat, Michel; Thuillez, Christian; Durand, Eric; Kadri, Zena; Steg, Philippe G

2006-04-10

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced. Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

Coffee consumption and the incidence of antihypertensive drug treatment in Finnish men and women.

PubMed

Hu, Gang; Jousilahti, Pekka; Nissinen, Aulikki; Bidel, Siamak; Antikainen, Riitta; Tuomilehto, Jaakko

2007-08-01

Only 2 prospective studies have previously investigated the association between coffee consumption and incident hypertension, and the findings are equivocal. The objective was to determine the relation between coffee consumption and the incidence of antihypertensive drug treatment. We prospectively followed 24 710 Finnish subjects aged 25-64 y without a history of antihypertensive drug treatment, coronary heart disease, or stroke at baseline. Daily coffee consumption was assessed by questionnaires. During a mean follow-up period of 13.2 y, 2505 participants started antihypertensive drug treatment. The multivariate-adjusted (age, sex, study year, education, leisure-time physical activity, smoking, body mass index, high total cholesterol, history of diabetes, and alcohol, tea, fruit, vegetable, sausage, and bread consumption) hazard ratios for antihypertensive drug treatment associated with the amount of coffee consumed daily (0-1, 2-3, 4-5, 6-7, or >or=8 cups) were 1.00, 1.29 (95% CI: 1.09, 1.54), 1.26 (95% CI: 1.06, 1.49), 1.24 (95% CI: 1.04, 1.48), and 1.14 (95% CI: 0.94, 1.37) (P for trend = 0.024), respectively. This trend became marginally significant after additional adjustment for baseline systolic blood pressure (P for trend = 0.077). The results indicate that coffee drinking seems to increase the risk of antihypertensive drug treatment, and this risk was higher in subjects with low-to-moderate coffee intakes; however, there was no significantly increased trend in drinkers of approximately 1 cup (100 mL)/d or >or=8 cups/d.

Neurocognitive Function in Children with Primary Hypertension after Initiation of Antihypertensive Therapy.

PubMed

Lande, Marc B; Batisky, Donald L; Kupferman, Juan C; Samuels, Joshua; Hooper, Stephen R; Falkner, Bonita; Waldstein, Shari R; Szilagyi, Peter G; Wang, Hongyue; Staskiewicz, Jennifer; Adams, Heather R

2018-04-01

To determine the change in neurocognitive test performance in children with primary hypertension after initiation of antihypertensive therapy. Subjects with hypertension and normotensive control subjects had neurocognitive testing at baseline and again after 1 year, during which time the subjects with hypertension received antihypertensive therapy. Subjects completed tests of general intelligence, attention, memory, executive function, and processing speed, and parents completed rating scales of executive function. Fifty-five subjects with hypertension and 66 normotensive control subjects underwent both baseline and 1-year assessments. Overall, the blood pressure (BP) of subjects with hypertension improved (24-hour systolic BP load: mean baseline vs 1 year, 58% vs 38%, P < .001). Primary multivariable analyses showed that the hypertension group improved in scores of subtests of the Rey Auditory Verbal Learning Test, Grooved Pegboard, and Delis-Kaplan Executive Function System Tower Test (P < .05). However, the control group also improved in the same measures with similar effects sizes. Secondary analyses by effectiveness of antihypertensive therapy showed that subjects with persistent ambulatory hypertension at 1 year (n = 17) did not improve in subtests of Rey Auditory Verbal Learning Test and had limited improvement in Grooved Pegboard. Overall, children with hypertension did not improve in neurocognitive test performance after 1 year of antihypertensive therapy, beyond that also seen in normotensive controls, suggesting improvements with age or practice effects because of repeated neurocognitive testing. However, the degree to which antihypertensive therapy improves BP may affect its impact upon neurocognitive function. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety of Temporary Discontinuation of Antihypertensive Medication in Patients With Difficult-to-Control Hypertension.

PubMed

Beeftink, Martine M A; van der Sande, Nicolette G C; Bots, Michiel L; Doevendans, Pieter A; Blankestijn, Peter J; Visseren, Frank L J; Voskuil, Michiel; Spiering, Wilko

2017-05-01

Successful control of blood pressure relies on identification of secondary causes and contributing factors of hypertension. As antihypertensive medication can interfere with diagnostic investigations, temporary discontinuation of medication is advised. However, there are concerns about the safety of temporary discontinuation of antihypertensive medication in patients with difficult-to-control hypertension. We assessed the occurrence of adverse cardiovascular and cerebrovascular events potentially attributable to temporary discontinuation of antihypertensive medication between February 2010 and March 2016 (n=604) in our Analysis of Complicated Hypertension screening program. A reference group (n=604) was extracted from the SMART study (Second Manifestations of Arterial Disease) cohort (comprising a similar cohort at our hospital in whom medication was not stopped) and individually matched for blood pressure, age, sex, and history of cardiovascular disease. Discontinuation of medication was well tolerated; 62% reported no complaints, 24% had mild discomfort that could be left untreated, and 14% experienced complaints that required prescription of antihypertensive escape medication. Three major adverse events were observed in the Analysis of Complicated Hypertension group between discontinuation of medication and 30 days after restart of medication (event rate=31.2 events per 1000 patient-year). In the reference cohort, 5 cardiovascular events were observed during a similar follow-up period (event rate=51.2 events per 1000 patient-year). In conclusion, discontinuation of antihypertensive medication for the diagnostic evaluation of hypertension does not increase the acute risk of cardiovascular events when performed in a well-controlled setting in specialized hospitals with appropriate protocols for monitoring safety. © 2017 American Heart Association, Inc.

Medical visits, antihypertensive prescriptions and medication adherence among newly diagnosed hypertensive patients in Korea.

PubMed

Jeong, Hyoseon; Kim, Hyeongsu; Lee, Kunsei; Lee, Jung Hyun; Ahn, Hye Mi; Shin, Soon Ae; Kim, Vitna

2017-03-17

The objective of this study was to assess the antihypertensive medication adherence in patients who were newly diagnosed with hypertension in Korea. Study subjects were diagnosed with hypertension for the first time by the General Health Screening in 2012 and were 65,919. As indices, visiting rate to medical institution, the antihypertensive prescription rate, medication possession ratio and the rate of appropriate medication adherence were used. The qualification data, the General Health Screening data and the health insurance claims data were used. Visiting rate to medical institution within one-year was 42.3%. Gender, age, family history of hypertension, smoking status, drinking frequency, insurance type, BMI, hypertension status, blood glucose level and LDL-cholesterol level were significant variables for visiting a medical institution. Of the study subjects who visited a medical institution, the antihypertensive prescription rate was 89.1%. Medication possession ratio was 70.9% and the rate of appropriate medication adherence was 60.6%. Age, family history of hypertension, smoking status, BMI level, hypertension level, blood glucose level, status, and LDL-cholesterol level were significant variables for the antihypertensive prescription and gender, age, family history of hypertension, smoking status, BMI, hypertension status, and the time of the first visit to a medical institution were significant variables for appropriate medication adherence. This study showed that the antihypertensive medication adherence in patients who were newly diagnosed with hypertension was not relatively high in Korea. National Health Insurance Service should support an environment in which medical institutions and those diagnosed with hypertension can fulfill their roles.

Antihypertensive drugs for elderly patients: a cross- sectional study

PubMed Central

Lim, Ka Keat; Sivasampu, Sheamini; Khoo, Ee Ming

2015-01-01

INTRODUCTION As the population ages, the prevalence of hypertension also increases. Although primary care is usually the patient’s first point of contact for healthcare, little is known about the management of hypertension among elderly patients at the primary care level. This study aimed to determine the antihypertensive prescription trend for elderly patients, the predictors of antihypertensive use and any inappropriate prescribing practices in both public and private primary care settings. METHODS Data on patient demographics, diagnosis, prescription pattern, payment mode and follow-up was extracted from a cross-sectional study involving 122 public primary care clinics and 652 private primary care clinics in Malaysia. Encounters with hypertensive patients aged ≥ 60 years were included. RESULTS A total of 1,017 antihypertensive medications were prescribed – calcium channel blockers (27.1%), beta blockers (25.5%), diuretics (23.3%), angiotensin-converting enzyme inhibitors (14.9%) and angiotensin receptor blockers (6.3%). Out of the 614 patient encounters, 53.1% of the patients were prescribed monotherapy, 31.6% were prescribed dual therapy, 12.2% triple therapy, 2.8% quadruple therapy and 0.3% quintuple therapy. Type of primary care clinic and payment mode were significant predictors for the prescription of combination therapy and fixed-dose combination therapy, respectively. Four types of inappropriate prescriptions were identified. CONCLUSION Calcium channel blockers were the most common antihypertensive drug prescribed and more than half of the elderly patients were on monotherapy. Antihypertensive drug prescription was found to be associated with the type of primary care clinic and the payment mode, suggesting that prescription is influenced by the cost of the drug. PMID:25597751

Changes in Antihypertensive Therapy After Renal Transplantation.

PubMed

Villanego, F; Moreno, A; Wu, J; Naranjo, J; Delgado, A; Cazorla, J M; Garcia, T; Mazuecos, A

2018-03-01

Post-transplant hypertension is extremely frequent, occurring in 60% to 90% of cases. It is involved in the pathogenesis of chronic graft dysfunction and patient survival. We sought to describe changes in antihypertensive therapy after renal transplantation (RT) depending on the type of pretransplant renal replacement therapy (RRT), hemodialysis (HD) or peritoneal dialysis (PD). We performed a retrospective cohort study of RT patients who were divided into 2 groups according to the type of pretransplant RRT (HD group: 69 patients; PD group: 38 patients). Patients with a diagnosis of nonessential hypertension etiology, diagnosis of renal artery stenosis of the graft, active urologic complications, and history of acute graft rejection were excluded. Variables related to chronic kidney disease and RT as well as antihypertensive therapy were studied. PD patients had reduced number of antihypertensive drugs at 1 month after RT (1.39 ± 1.03) compared with pre-RT (2.16 ± 1.30; P = .001), a trend that was maintained at 6 months (1.70 ± 1.18; P = .06). In HD group, the number of antihypertensive drugs increased at 6 months after RT (1.59 ± 1.17) compared with pretransplant (1.15 ± 1.13; P = .027). The use of calcium channel blockers increased by 10.2% by 1 month (P = .071) and 9.2% (P = .036) by 6 months after RT. By 1 month after RT, antihypertensive therapy was reduced. Calcium channel blockers were the most common drug group, although it is usually necessary to use more than 1 drug. Copyright © 2017 Elsevier Inc. All rights reserved.

Field trial of GABA-fortified rice plants and oral administration of milled rice in spontaneously hypertensive rats.

PubMed

Kowaka, Emi; Shimajiri, Yasuka; Kawakami, Kouhei; Tongu, Miki; Akama, Kazuhito

2015-06-01

Hypertension is one of the most critical risk factors accompanying cardiovascular diseases. γ-Aminobutyric acid (GABA) is a non-protein amino acid that functions as a major neurotransmitter in mammals and also as a blood-pressure lowering agent. We previously produced GABA-fortified rice lines of a popular Japonica rice cultivar 'Koshihikari' by genetic manipulation of GABA shunt-related genes. In the study reported here, we grew these same novel rice lines in a field trial and administered the milled rice orally to rats. The yield parameters of the transgenic rice plants were almost unchanged compared to those of untransformed cv. 'Koshihikari' plants, while the rice grains of the transgenic plants contained a high GABA content (3.5 g GABA/kg brown rice; 0.75-0.85 GABA g/kg milled rice) in a greenhouse trial. Oral administration of a diet containing 2.5% GABA-fortified rice, with a daily intake for 8 weeks, had an approximately 20 mmHg anti-hypertensive effect in spontaneous hypertensive rats but not in normotensive Wistar-Kyoto rats. These results suggest that GABA-fortified rice may be applicable as a staple food to control or prevent hypertension.

Physicians' choice in using Internet and fax for patient recruitment and follow-up in a randomized controlled trial.

PubMed

Rahman, M; Morita, S; Fukui, T; Sakamoto, J

2004-01-01

To examine the physicians' preference between Web and fax-based remote data entry (RDE) system for an ongoing randomized controlled trial (RCT) in Japan. We conducted a survey among all the collaborating physicians (n = 512) of the CASE-J (Candesartan Antihypertensive Survival Evaluation in Japan) trial, who have been recruiting patients and sending follow-up data using the Web or a fax-based RDE system. The survey instrument assessed physicians' choice between Web and fax-based RDE systems, their practice pattern, and attitudes towards these two modalities. A total of 448 (87.5%) responses were received. The proportions of physicians who used Web, fax, and the combination of these two were 45.9%, 33.3% and 20.8%, respectively. Multivariate logistic regression analyses revealed that physicians 55 years or younger [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.3] and regular users of computers (OR = 4.2, 95% CI = 2.1-8.2) were more likely to use the Web-based RDE system. This information would be useful in designing an RCT with a Web-based RDE system in Japan and abroad.

Patient characteristics associated with greater blood pressure control in a randomized trial of home blood pressure telemonitoring and pharmacist management.

PubMed

Asche, Stephen E; O'Connor, Patrick J; Dehmer, Steven P; Green, Beverly B; Bergdall, Anna R; Maciosek, Michael V; Nyboer, Rachel A; Pawloski, Pamala A; Sperl-Hillen, JoAnn M; Trower, Nicole K; Margolis, Karen L

2016-11-01

This paper reports subgroup analysis of a successful cluster-randomized trial to identify attributes of hypertensive patients who benefited more or less from an intervention combining blood pressure (BP) telemonitoring and pharmacist management. The end point was BP < 140/90 mm Hg at 6-month follow-up. Fourteen baseline patient characteristics were selected a priori as subgroup variables. Among the 351 trial participants, 44% were female, 84% non-Hispanic white, mean age was 60.9 years, and mean BP was 149/86 mm Hg. The overall adjusted odds ratio for BP control in the intervention versus usual care group was 3.64 (P < .001). The effect of the intervention was significantly larger in patients who were younger (interaction P = .02), did not have diabetes (P = .005), had high baseline diastolic BP (P = .02), added salt less than daily in food preparation (P = .007), and took 0-2 (rather than 3-6) antihypertensive medication classes at baseline (P = .02). These findings may help prioritize patients for whom the intervention is most effective. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Recruitment process of a Chinese immigrant study in Canada.

PubMed

Zou, Ping

2017-08-01

The objectives of this article were to provide a comprehensive overview of the recruitment experience and participant characteristics in an antihypertensive dietary educational intervention pilot trial among Chinese Canadians. The recruitment was conducted in a community centre. Two recruitment approaches, self-referral and proactive recruitment, were used. Among 618 Chinese Canadians in the blood pressure screening, 105 (17.0%) individuals were eligible to participate in this trial. Of the 105 eligible individuals, 45 (42.9%) declined enrollment and 60 (57.1%) consented to participate in the trial and were recruited. The most common reason for refusal was being unable to access to the education location (n=19, 42.2%) followed by being too busy to participate (n=18, 40.0%). All participants were Chinese immigrants and the mean number of years living in Canada was 9.2. Most participants had low English proficiency, accepted Chinese culture more than Western culture, and had strong traditional health beliefs. It is concluded that both self-referral and proactive recruitment approaches were effective. Home-based interventions using Internet and telephone should be used as alternative delivery approaches to improve recruitment rate and facilitate participation. Copyright © 2017 Elsevier Inc. All rights reserved.

A quality improvement plan for hypertension control: the INCOTECA Project (INterventions for COntrol of hyperTEnsion in CAtalonia)

PubMed Central

Vallès-Fernandez, Roser; Rosell-Murphy, Magdalena; Correcher-Aventin, Olga; Mengual-Martínez, Lucas; Aznar-Martínez, Núria; Prieto-De Lamo, Gemma; Franzi-Sisó, Alícia; Puig-Manresa, Jordi; Ma Bonet-Simó, Josep

2009-01-01

Background Different studies have shown insufficient blood pressure (BP) control in hypertensive patients. Multiple factors influence hypertension management, and the quality of primary care is one of them. We decided therefore to evaluate the effectiveness of a quality improvement plan directed at professionals of Primary Health Care Teams (PHCT) with the aim to achieve a better control of hypertension. The hypothesis of the study is that the implementation of a quality improvement plan will improve the control of hypertension. The primary aim of this study will be to evaluate the effectiveness of this plan. Methods and design Design: multicentric study quasi-experimental before – after with control group. The non-randomised allocation of the intervention will be done at PHCT level. Setting: 18 PHCT in the Barcelona province (Spain). Sample: all patients with a diagnosis of hypertension (population based study). Exclusion criteria: patients with a diagnosis of hypertension made later than 01/01/2006 and patients younger than 18 years. Intervention: a quality improvement plan, which targets primary health care professionals and includes educational sessions, feedback to health professionals, audit and implementation of recommended clinical practice guidelines for the management of hypertensive patients. Measurements: age, sex, associated co-morbidity (diabetes mellitus type I and II, heart failure and renal failure). The following variables will be recorded: BP measurement, cardiovascular risk and antihypertensive drugs used. Results will be measured before the start of the intervention and twelve months after the start of the study. Dependent variable: prevalence of hypertensive patients with poor BP control. Analysis: Chi-square test and Student's t-test will be used to measure the association between independent qualitative and quantitative variables, respectively. Non-parametric tests will be used for the analysis of non-normally distributed variables. Significance level (α) will be set at < 0.05. Outcomes will be analysed on an intention-to-treat basis. Discussion The implementation of a quality improvement plan might benefit the coordination of different professionals of PHCTs and may also improve blood pressure control. Trial Registration This protocol has been registered at clinicaltrials.gov with the ID number MS: 1998275938244441. PMID:19321009

Combining neuroendocrine inhibitors in heart failure: reflections on safety and efficacy.

PubMed

Jneid, Hani; Moukarbel, George V; Dawson, Bart; Hajjar, Roger J; Francis, Gary S

2007-12-01

Neuroendocrine activation in heart failure has become the major target of pharmacotherapy for this growing epidemic. Agents targeting the renin-angiotensin-aldosterone and sympathetic nervous systems have shown cardiovascular and survival benefits in clinical trials. Beta-blockers and angiotensin-converting enzyme (ACE) inhibitors remain the mainstream initial therapy. The benefits of aldosterone antagonists have been demonstrated in advanced heart failure (spironolactone) and after myocardial infarction complicated by left ventricular dysfunction and heart failure (eplerenone). Emerging clinical evidence demonstrated that angiotensin receptor blockers may be a reasonable alternative to ACE inhibitors in patients with heart failure (candesartan) and following myocardial infarction complicated by heart failure or left ventricular dysfunction (valsartan). Angiotensin receptor blockers (candesartan) also provided incremental benefits when added to ACE inhibitors in chronic heart failure. Thus, combining neuroendocrine inhibitors in heart failure appears both biologically plausible and evidence-based. However, this approach raised concerns about side effects, such as hypotension, renal insufficiency, hyperkalemia, and others. Close follow-up and implementation of evidence-based medicine (ie, using agents and doses proven beneficial in clinical trials) should therefore be undertaken when combining neuroendocrine inhibitors.

Assessment and prevalence of pulmonary oedema in contemporary acute heart failure trials: a systematic review.

PubMed

Platz, Elke; Jhund, Pardeep S; Campbell, Ross T; McMurray, John J

2015-09-01

Pulmonary oedema is a common and important finding in acute heart failure (AHF). We conducted a systematic review to describe the methods used to assess pulmonary oedema in recent randomized AHF trials and report its prevalence in these trials. Of 23 AHF trials published between 2002 and 2013, six were excluded because they were very small or not randomized, or missing full-length publications. Of the remaining 17 (n = 200-7141) trials, six enrolled patients with HF and reduced ejection fraction (HF-REF) and 11, patients with both HF-REF and HF with preserved ejection fraction (HF-PEF). Pulmonary oedema was an essential inclusion criterion, in most trials, based upon findings on physical examination ('rales'), radiographic criteria ('signs of congestion'), or both. The prevalence of pulmonary oedema in HF-REF trials ranged from 75% to 83% and in combined HF-REF and HF-PEF trials from 51% to 100%. Five trials did not report the prevalence or extent of pulmonary oedema assessed by either clinical examination or chest x-ray. Improvement of pulmonary congestion with treatment was inconsistently reported and commonly grouped with other signs of congestion into a score. One trial suggested that patients with rales over >2/3 of the lung fields on admission were at higher risk of adverse outcomes than those without. Although pulmonary oedema is a common finding in AHF, represents a therapeutic target, and may be of prognostic importance, recent trials used inconsistent criteria to define it, and did not consistently report its severity at baseline or its response to treatment. Consistent and ideally quantitative, methods for the assessment of pulmonary oedema in AHF trials are needed. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.