Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation

David P. Kao, Gordon Davis, Ryan Aleong, Christopher M. O'Connor, Mona Fiuzat, Peter E. Carson, Inder S. Anand, Jonathan F. Plehn, Stephen S. Gottlieb, Marc A. Silver, Joann Lindenfeld, Alan B. Miller, Michel White, Guinevere A. Murphy, Will Sauer, Michael R. Bristow

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

AimsThere is little evidence of beta-blocker treatment benefit in patients with heart failure and reduced left ventricular ejection fraction (HFREF) and atrial fibrillation (AF). We investigated the effects of bucindolol in HFREF patients with AF enrolled in the Beta-blocker Evaluation of Survival Trial (BEST).Methods and resultsA post-hoc analysis of patients in BEST with and without AF was performed to estimate the effect of bucindolol on mortality and hospitalization. Patients were also evaluated for treatment effects on heart rate and the influence of beta1-adrenergic receptor position 389 (β1389) arginine (Arg) vs. glycine (Gly) genotypes. In the 303/2708 patients in AF, patients receiving bucindolol were more likely to achieve a resting heart rate ≤80 b.p.m. at 3 months (P < 0.005) in the absence of treatment-limiting bradycardia. In AF patients and sinus rhythm (SR) patients who achieved a resting heart rate ≤80 b.p.m., there were beneficial treatment effects on cardiovascular mortality/cardiovascular hospitalization [hazard ratio (HR) 0.61, P = 0.025, and 0.79, P = 0.002]. Without achieving a resting heart rate ≤80 b.p.m., there were no treatment effects on events in either group. β1389-Arg/Arg AF patients had nominally significant reductions in all-cause mortality/HF hospitalization and cardiovascular mortality/hospitalization with bucindolol (HR 0.23, P = 0.037 and 0.28, P = 0.039), whereas Gly carriers did not. There was no evidence of diminished heart rate response in β1389-Arg homozygotes. ConclusionIn HFREF patients with AF, bucindolol was associated with reductions in composite HF endpoints in those who achieved a resting heart rate ≤80 b.p.m. and nominally in those with the β1389-Arg homozygous genotype.

Original languageEnglish (US)
Pages (from-to)324-333
Number of pages10
JournalEuropean Journal of Heart Failure
Volume15
Issue number3
DOIs
StatePublished - Mar 1 2013

Keywords

  • Atrial fibrillation
  • Beta -adrenergic receptor polymorphism
  • Beta-blocker
  • Bucindolol
  • Heart failure

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