A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure

N Engl J Med. 2001 May 31;344(22):1659-67. doi: 10.1056/NEJM200105313442202.


Background: Although beta-adrenergic-receptor antagonists reduce morbidity and mortality in patients with mild-to-moderate chronic heart failure, their effect on survival in patients with more advanced heart failure is unknown.

Methods: A total of 2708 patients with heart failure designated as New York Heart Association (NYHA) functional class III (in 92 percent of the patients) or IV (in 8 percent) and a left ventricular ejection fraction of 35 percent or lower were randomly assigned to double-blind treatment with either bucindolol (1354 patients) or placebo (1354 patients) and followed for the primary end point of death from any cause.

Results: The data and safety monitoring board recommended stopping the trial after the seventh interim analysis. At that time, there was no significant difference in mortality between the two groups (unadjusted P=0.16). The results presented here are based on complete follow-up at the time of study termination (average, 2.0 years). There were a total of 449 deaths in the placebo group (33 percent) and 411 deaths in the bucindolol group (30 percent; adjusted P=0.13). The risk of the secondary end point of death from cardiovascular causes was lower in the bucindolol group (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99), as was the risk of heart transplantation or death (hazard ratio, 0.87; 95 percent confidence interval, 0.77 to 0.99).

Conclusions: In a demographically diverse group of patients with NYHA class III and IV heart failure, bucindolol resulted in no significant overall survival benefit.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Chronic Disease
  • Double-Blind Method
  • Female
  • Heart Failure / classification
  • Heart Failure / drug therapy*
  • Heart Failure / ethnology
  • Heart Failure / mortality
  • Heart Transplantation / statistics & numerical data
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Propanolamines / adverse effects
  • Propanolamines / therapeutic use*
  • Proportional Hazards Models
  • Severity of Illness Index
  • Survival Analysis


  • Adrenergic beta-Antagonists
  • Propanolamines
  • bucindolol