Safety and efficacy of carvedilol in severe heart failure. The U.S. Carvedilol Heart Failure Study Group

J Card Fail. 1997 Sep;3(3):173-9. doi: 10.1016/s1071-9164(97)90013-0.


Background: Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function.

Methods and results: One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8%) did not complete the open-label period because of adverse events and 11.4% in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P < .05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004).

Conclusion: The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.

Publication types

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

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Carbazoles / pharmacology
  • Carbazoles / therapeutic use*
  • Carvedilol
  • Double-Blind Method
  • Female
  • Heart Failure / classification
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Hemodynamics / drug effects
  • Humans
  • Male
  • Middle Aged
  • Propanolamines / pharmacology
  • Propanolamines / therapeutic use*
  • Prospective Studies
  • Quality of Life


  • Adrenergic beta-Antagonists
  • Carbazoles
  • Propanolamines
  • Carvedilol