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Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation
Author(s) -
Kao David P.,
Davis Gordon,
Aleong Ryan,
O'Connor Christopher M.,
Fiuzat Mona,
Carson Peter E.,
Anand Inder S.,
Plehn Jonathan F.,
Gottlieb Stephen S.,
Silver Marc A.,
Lindenfeld JoAnn,
Miller Alan B.,
White Michel,
Murphy Guinevere A.,
Sauer Will,
Bristow Michael R.
Publication year - 2013
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfs181
Subject(s) - medicine , heart failure , ejection fraction , cardiology , atrial fibrillation , hazard ratio , heart rate , ivabradine , sinus rhythm , bradycardia , post hoc analysis , blood pressure , confidence interval
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 beta 1 ‐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.