title: Safety and efficacy of carvedilol in severe heart failure. The U.S. Carvedilol Heart Failure Study Group.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiovascular Division, University of Minnesota Medical School, Minneapolis 55455, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Cohn
authors.forename: M B
authors.initials: MB
authors.lastname: Fowler
authors.forename: M R
authors.initials: MR
authors.lastname: Bristow
authors.forename: W S
authors.initials: WS
authors.lastname: Colucci
authors.forename: E M
authors.initials: EM
authors.lastname: Gilbert
authors.forename: V
authors.initials: V
authors.lastname: Kinhal
authors.forename: S K
authors.initials: SK
authors.lastname: Krueger
authors.forename: T
authors.initials: T
authors.lastname: Lejemtel
authors.forename: K A
authors.initials: KA
authors.lastname: Narahara
authors.forename: M
authors.initials: M
authors.lastname: Packer
authors.forename: S T
authors.initials: ST
authors.lastname: Young
authors.forename: T L
authors.initials: TL
authors.lastname: Holcslaw
authors.forename: M A
authors.initials: MA
authors.lastname: Lukas
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D011788:Quality of Life
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol