Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation. (March 2013)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: European journal of heart failure. Volume 15:Number 3(2013)
• Page Start: 324
• Page End: 333
• Publication Date: 2013-03
• Subjects: Heart failure -- Periodicals; Heart Failure -- Periodicals; Insuffisance cardiaque -- Périodiques; Heart failure; Periodicals; 616.129005
• DOI: 10.1093/eurjhf/hfs181
• Languages: English
• ISSNs: 1388-9842

Abstract

<abstract abstract-type="main" id="ejhfhfs181-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ejhfhfs181-sec-0001" sec-type="section"> <title>Aims</title> <p>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).</p> </sec> <sec id="ejhfhfs181-sec-0002" sec-type="section"> <title>Methods and results</title> <p>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<sub>1</sub>‐adrenergic receptor position 389 (β<sub>1</sub>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 (<italic>P</italic> < 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, <italic>P</italic> = 0.025, and 0.79, <italic>P</italic> = 0.002]. Without achieving a resting heart rate ≤80 b.p.m., there were no treatment effects on events in either group. β<sub>1</sub>389‐Arg/Arg AF patients had nominally significant reductions in all‐cause mortality/HF hospitalization and cardiovascular mortality/hospitalization with bucindolol (HR 0.23, <italic>P</italic> = 0.037 and 0.28, <italic>P</italic> = 0.039), whereas Gly carriers did not. There was no evidence of diminished heart rate response in β<sub>1</sub>389‐Arg homozygotes.</p> </sec> <sec id="ejhfhfs181-sec-0003" sec-type="section"> <title>Conclusion</title> <p>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<sub>1</sub>389‐Arg homozygous genotype.</p> </sec> </abstract>