title: Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Kao
authors.forename: Gordon
authors.initials: G
authors.lastname: Davis
authors.forename: Ryan
authors.initials: R
authors.lastname: Aleong
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.forename: Peter E
authors.initials: PE
authors.lastname: Carson
authors.forename: Inder S
authors.initials: IS
authors.lastname: Anand
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Plehn
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Gottlieb
authors.forename: Marc A
authors.initials: MA
authors.lastname: Silver
authors.forename: JoAnn
authors.initials: J
authors.lastname: Lindenfeld
authors.forename: Alan B
authors.initials: AB
authors.lastname: Miller
authors.forename: Michel
authors.initials: M
authors.lastname: White
authors.forename: Guinevere A
authors.initials: GA
authors.lastname: Murphy
authors.forename: Will
authors.initials: W
authors.lastname: Sauer
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bristow
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016022:Case-Control Studies; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006339:Heart Rate / Q000187:drug effects; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011412:Propanolamines / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: C547787:ADRB1 protein, human; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; C024307:bucindolol