title: Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure--COMET.
abstract: BACKGROUND
  Beta-blockers with different receptor bindings reduce mortality in patients with chronic heart failure. We compared the effects of the beta1-blocker metoprolol tartrate and the beta1-, beta2-, and alpha1-blocker carvedilol.
  
  
  METHODS
  In a randomized double-blind design, 3029 patients with chronic congestive heart failure requiring diuretic therapy and with left ventricular dysfunction were randomized to treatment with carvedilol (n = 1511) or metoprolol tartrate (n = 1518) and titrated to target doses of 25 mg of carvedilol twice daily or 50 mg of metoprolol tartrate twice daily. The main outcome measures were total mortality and the combination of mortality or hospitalization for any cause. Secondary end points were cardiovascular death, combinations of morbidity and mortality, New York Heart Association class, worsening of heart failure, hospitalizations, and discontinuation of study therapy.
  
  
  RESULTS
  A total of 512 and 600 patients in the carvedilol group and metoprolol group, respectively, died (hazard ratio [HR] 0.83, 95% CI 0.74-0.93, P = .0017). Cardiovascular death was reduced by carvedilol (HR 0.80, 95% CI 0.70-0.90, P = .0004). There were fewer sudden deaths and deaths caused by circulatory failure or by stroke in the carvedilol group. There was no difference in all-cause hospitalizations or in worsening heart failure between treatment groups. The incidence of fatal or nonfatal acute myocardial infarction was significantly lower in the carvedilol group (HR 0.71, 95% CI 0.52-0.97, P = .03). Discontinuations of study therapy were similar in the 2 groups.
  
  
  CONCLUSIONS
  Compared with metoprolol tartrate, carvedilol reduced cardiovascular mortality, sudden death, death caused by circulatory failure, death caused by stroke, as well as fatal and nonfatal myocardial infarctions.
authors.affiliation: Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark. ctp@heart.dk
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: Philip A
authors.initials: PA
authors.lastname: Poole-Wilson
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Lenarda
authors.forename: Peter
authors.initials: P
authors.lastname: Hanrath
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.forename: Beatrix
authors.initials: B
authors.lastname: Lutiger
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.forename: Willem J
authors.initials: WJ
authors.lastname: Remme
authors.forename: Armin
authors.initials: A
authors.lastname: Scherhag
authors.forename: Allan
authors.initials: A
authors.lastname: Skene
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D011412:Propanolamines / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol