Beta-blocker pharmacogenetics in heart failure.
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ABSTRACT:
SUBMITTER: Shin J
PROVIDER: S-EPMC2851851 | biostudies-literature | 2010 May
REPOSITORIES: biostudies-literature
Publications
Beta-blocker pharmacogenetics in heart failure.
Shin Jaekyu J Johnson Julie A JA
Heart failure reviews 20080424 3
Beta-blockers (metoprolol, bisoprolol, and carvedilol) are a cornerstone of heart failure (HF) treatment. However, it is well recognized that responses to a beta-blocker are variable among patients with HF. Numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to a beta-blocker, including left ventricular ejection fraction improvement, survival, and hospitalization due to HF exacerbation. This review summarizes the pharmacogenetic data for beta-blocke ...[more]
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Project description:Backgroundβ-blockers (BBs) are considered primary therapy in stable heart failure (HF) with reduced ejection fraction (HFrEF) without atrial fibrillation (AF); evidence-based benefits of BB on outcome have been documented. However, BBs have not been shown to improve mortality or reduce hospital admissions in HF patients with AF. This study assessed the relationship between BBs at discharge and relevant clinical outcomes in acute heart failure (AHF) patients with AF.MethodsFrom the Korean Acute Heart Failure Registry, 936 HFrEF and 639 HF patients with preserved ejection fraction (HFpEF) and AF were selected. Propensity score (PS) matching accounted for BB selection bias when assessing associations.ResultsBB-untreated patients in the overall cohort of HFrEF and HFpEF had greater deteriorated clinical and laboratory characteristics. In the 670 PS-matched cohort of HFrEF patients, incidences of all clinical events at 60 days and 1 year were not different according to use of BBs. In the 470 PS-matched cohort of HFpEF, rehospitalization and composite outcome at 6 months and 1 year more frequently occurred in non-users of BBs. After adjusting for covariates in the multivariable Cox model of matched cohorts, BB was not associated with clinical outcomes at 60 days and 1 year in HFrEF with AF patients. In HFpEF patients with AF, BB use was associated with reduced 6-month (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.74) and 1-year rehospitalization (HR, 0.53; 95% CI, 0.34-0.82).ConclusionIn the HFrEF with AF PS-matched cohort, the use of BBs at discharge was not associated with clinical outcome. However, in HFpEF with AF, the use of BB was associated with reduced rehospitalization during the 6-month and 1-year follow up.
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Project description:Heart failure is an increasingly common disease associated with significant morbidity and mortality in the aging population. Recent advances in heart failure pharmacotherapy have established several agents as beneficial to disease progression and outcomes. However, current consensus guideline-recommended pharmacotherapy may not represent an optimal treatment strategy in all heart failure patients. Specifically, individuals with genetic variation in regions central to mediation of beneficial response to standard heart failure agents may not receive optimal benefit from these drugs. Additionally, targeted approaches in phase 3 clinical trials that select patients for inclusion based on the genotype most likely to respond might advance the currently stalled drug development pipeline in heart failure. This article reviews the literature in heart failure pharmacogenetics to date, opportunities for discovery in recent and upcoming clinical trials, as well as future directions in this field.
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Project description:This study sought to evaluate the effects of beta-blocker withdrawal in acute decompensated heart failure (ADHF).Published reports showed trends for either no harm or increased risk of in-hospital mortality, short-term mortality, and rehospitalization rates in patients admitted for ADHF that discontinued beta-blockers; however, a comprehensive analysis has not been conducted.Relevant studies from January 2000 through January 2015 were identified in the PubMed, EMBASE, and COCHRANE electronic databases. Where appropriate data were available, weighted relative risks were estimated using random-effects meta-analysis techniques.Five observational studies and 1 randomized clinical trial (n = 2,704 patients who continued beta-blocker therapy and n = 439 patients who discontinued beta-blocker therapy) that reported the short-term effects of beta-blocker withdrawal in ADHF were included in the analyses. In 2 studies, beta-blocker withdrawal significantly increased risk of in-hospital mortality (risk ratio: 3.72; 95% confidence interval [CI]: 1.51 to 9.14). Short-term mortality (relative risk: 1.61; 95% CI: 1.04 to 2.49; 4 studies) and combined short-term rehospitalization or death (relative risk: 1.59; 95% CI: 1.03 to 2.45; 4 studies) were also significantly increased.Discontinuation of beta-blockers in patients admitted with ADHF was associated with significantly increased in-hospital mortality, short-term mortality, and the combined endpoint of short-term rehospitalization or mortality. These data suggest beta-blockers should be continued in ADHF patients if their clinical picture allows.
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Project description:To assess whether beta-blocker use is associated with cardiovascular events and mortality in patients with heart failure with preserved ejection fraction (HFpEF), this study analyzed the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial data using Cox proportional hazard models. Adjusted HRs for composite cardiovascular events in all patients and in patients without previous MI were significantly higher for those on beta-blockers than for those not on beta-blockers (Hazard ratio [HR] for all patients 1.23, 95% confidence interval [95% CI] 1.02-1.49; HR for patients without previous MI 1.35, 95% CI 1.08-1.70), whereas that for patients with previous MI was not significantly different (HR 1.06, 95% CI 0.74-1.54). Additionally, cardiovascular event risk in propensity score-matched patients without previous MI was significantly higher in those on beta-blockers than in those not on beta-blockers. Risks of all-cause death, major cardiovascular events, and heart failure hospitalization were significantly higher in those on beta-blockers than in those not on beta-blockers. Beta-blocker use in HFpEF patients, particularly those without previous MI, was associated with increased risk of unfavorable cardiovascular events.
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