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.
Bibliographical noteFunding Information:
From the *University of Minnesota Medical School, Minneapolis, Minnesota; 7-Stanford University School of Medicine, Palo Alto, California; SUniversity of Colorado Health Sciences Center, Denver, Colorado; §Boston University School of Medicine, Boston, Massachusetts; I1 University of Utah School of Medicine, Salt Lake City, Utah; #Pierson Clinic, Grosse Pointe Shores, Michigan; §Nebraska Heart Institute, Lincoln, Nebraska; **Albert Einstein College of Medicine, Bronx, New York; "~'Harbor-UCLA Medical Center, Torrance, California; $¢Columbia Presbyterian Medical Center, New York, New York; and §§SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania. The Carvedilol Heart Failure Study Group Investigators are listed in the appendix. Supported by SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, and Boehringer Mannheim Therapeutics, Mannheim, Germany. Manuscript received Jan. 10, 1997; revised manuscript received April 1, 1997; accepted April 10, 1997. All editorial decisions for this article, including selection of referees, were made by a guest editor. This policy applies to all articles with authors from the University of Minnesota. Reprint requests: Jay N. Cohn, MD, Cardiovascular Division, University of Minnesota Medical School, Box 508 UMHC, 420 Delaware Street SE, Minneapolis, MN 55455. ©1997 Churchill Livingstone Inc.
- Heart failure
- Quality of life