Failure of benefit and early hazard of bucindolol for Class IV heart failure

J Card Fail. 2003 Aug;9(4):266-77. doi: 10.1054/jcaf.2003.42.


Objectives: The risks and benefits of beta-blockade with bucindolol were assessed in heart failure (HF) patients with Class IV symptoms within the Beta-blocker Evaluation of Survival Trial (BEST).

Background: beta-blockade is accepted therapy for mild to moderate HF, but its safety and efficacy in advanced HF have not been established.

Methods: BEST recruited 2708 HF patients; of these, 226 with Class IV symptoms (n=114 randomized to bucindolol, n=112 to placebo) formed the basis of this study. All-cause death, HF hospitalization, and drug discontinuations occurring early during therapy (< or =6 months) and overall during follow-up were assessed. Compared with Class III, Class IV patients were older and had higher plasma norepinephrine levels, prevalence of coronary disease, S3 gallops, and lower ejection fractions, but characteristics of the 2 Class IV treatment groups were similar.

Results: During a mean of 1.6 years, 49% Class IV patients died, and 54% were hospitalized for HF. Bucindolol increased the combined endpoint of death or HF hospitalization within the first 6 months (hazard ratio [HR]=1.7, 95% confidence interval [CI]=1.1-2.7) and did not result in benefit overall (HR=1.2, 95% CI=0.9-1.6). HF hospitalization alone within 6 months was increased by bucindolol (HR=1.7), and an early adverse trend for death was seen (HR=1.6) with no benefit overall (HR=1.1). Bucindolol was discontinued more frequently than placebo for worsening HF (11% versus 4%) and hypotension (3% versus 0%).

Conclusions: Class IV HF patients in BEST were at high risk. Bucindolol did not reduce death or HF hospitalization and was associated with early hazard.

Publication types

  • Clinical Trial
  • Comparative 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
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Cause of Death
  • Endpoint Determination
  • Female
  • Follow-Up Studies
  • Heart Failure / mortality
  • Heart Failure / therapy*
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prevalence
  • Propanolamines / adverse effects
  • Propanolamines / therapeutic use*
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Stroke Volume / physiology
  • Survival Analysis
  • Time
  • Time Factors
  • Treatment Failure


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Propanolamines
  • bucindolol