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

Background: Although beta-adrenergic-receptor antagonists reduce morbidity and mortality in patients with mild-to-moderate chronic heart failure, thei r effect on survival in patients with more advanced heart failure is unknow n. Methods: A total of 2708 patients with heart failure designated as New York Heart Association (NYHA) functional class III (in 92 percent of the patien ts) or IV (in 8 percent) and a left ventricular ejection fraction of 35 per cent 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 tria l after the seventh interim analysis. At that time, there was no significan t difference in mortality between the two groups (unadjusted P=0.16). The r esults 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 p lacebo group (33 percent) and 411 deaths in the bucindolol group (30 percen t, adjusted P=0.13). The risk of the secondary end point of death from card iovascular 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 trans plantation or death. In a subgroup analysis, there was a survival benefit i n nonblack patients. Conclusions: In a demographically diverse group of patients with NYHA class III and IV heart failure, bucindolol resulted in no significant overall su rvival benefit. (N Engl J Med 2001;344:1659-67.) Copyright (C) 2001 Massach usetts Medical Society.