Document Detail

Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation.
MedLine Citation:
PMID:  23223178     Owner:  NLM     Status:  MEDLINE    
AIMS: There 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 RESULTS: A 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 (β(1)389) 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. β(1)389-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 β(1)389-Arg homozygotes.
CONCLUSION: In 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 β(1)389-Arg homozygous genotype.
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
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-12-07
Journal Detail:
Title:  European journal of heart failure     Volume:  15     ISSN:  1879-0844     ISO Abbreviation:  Eur. J. Heart Fail.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-21     Completed Date:  2013-08-09     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  324-33     Citation Subset:  IM    
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MeSH Terms
Adrenergic beta-Antagonists / therapeutic use*
Atrial Fibrillation / complications,  drug therapy*,  mortality
Case-Control Studies
Drug Resistance / genetics
Heart Failure / complications,  drug therapy*,  mortality
Heart Rate / drug effects
Hospitalization / statistics & numerical data
Kaplan-Meier Estimate
Middle Aged
Polymorphism, Single Nucleotide
Propanolamines / therapeutic use*
Proportional Hazards Models
Receptors, Adrenergic, beta-1 / genetics
Retrospective Studies
Treatment Outcome
Grant Support
2 T32 HL007822-12/HL/NHLBI NIH HHS; L30 HL110124/HL/NHLBI NIH HHS; T32 HL007822/HL/NHLBI NIH HHS
Reg. No./Substance:
0/ADRB1 protein, human; 0/Adrenergic beta-Antagonists; 0/Propanolamines; 0/Receptors, Adrenergic, beta-1; E9UO06K7CE/bucindolol

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