title: Double-blind, placebo-controlled study of the long-term efficacy of carvedilol in patients with severe chronic heart failure.
abstract: BACKGROUND
  Clinical trials have shown that beta-adrenergic blocking drugs are effective and well tolerated in patients with mild to moderate heart failure, but the utility and safety of these drugs in patients with advanced disease have not been evaluated.
  
  
  RESULTS
  We enrolled 56 patients with severe chronic heart failure into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had advanced heart failure, as evidenced by a mean left ventricular ejection fraction of 0.16 +/- 0.01 and a mean maximal oxygen consumption of 13.6 +/- 0.6 mL.kg-1.min-1 despite digitalis, diuretics, and an angiotensin-converting enzyme inhibitor (if tolerated). After a 3-week, open-label, up-titration period, 49 of the 56 patients were assigned (in a double-blind fashion using a 2:1 randomization) to receive either carvedilol (25 mg BID, n = 33) or matching placebo (n = 16) for 14 weeks, while background therapy remained constant. Hemodynamic and functional variables were measured at the start and end of the study. Compared with the placebo group, patients in the carvedilol group showed improved cardiac performance, as reflected by an increase in left ventricular ejection fraction (P = .005) and stroke volume index (P = .010) and a decrease in pulmonary wedge pressure, mean right atrial pressure, and systemic vascular resistance (P = .003, .002, and .017, respectively). In addition, compared with placebo, patients treated with carvedilol benefited clinically, as shown by an improvement in symptom scores (P = .002), functional class (P = .013), and submaximal exercise tolerance (P = .006). The combined risk of death, worsening heart failure, and life-threatening ventricular tachyarrhythmia was lower in the carvedilol group than in the placebo group (P = .028), but carvedilol-treated patients had more dizziness and advanced heart block.
  
  
  CONCLUSIONS
  Carvedilol produces clinical and hemodynamic improvement in patients who have severe heart failure despite treatment with angiotensin-converting enzyme inhibitors.
authors.affiliation: Division of Circulatory Physiology, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
authors.forename: H
authors.initials: H
authors.lastname: Krum
authors.forename: J D
authors.initials: JD
authors.lastname: Sackner-Bernstein
authors.forename: R L
authors.initials: RL
authors.lastname: Goldsmith
authors.forename: M L
authors.initials: ML
authors.lastname: Kukin
authors.forename: B
authors.initials: B
authors.lastname: Schwartz
authors.forename: J
authors.initials: J
authors.lastname: Penn
authors.forename: N
authors.initials: N
authors.lastname: Medina
authors.forename: M
authors.initials: M
authors.lastname: Yushak
authors.forename: E
authors.initials: E
authors.lastname: Horn
authors.forename: S D
authors.initials: SD
authors.lastname: Katz
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol