title: Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial.
abstract: BACKGROUND
  Beta blockers reduce mortality in patients who have chronic heart failure, systolic dysfunction, and are on background treatment with diuretics and angiotensin-converting enzyme inhibitors. We aimed to compare the effects of carvedilol and metoprolol on clinical outcome.
  
  
  METHODS
  In a multicentre, double-blind, and randomised parallel group trial, we assigned 1511 patients with chronic heart failure to treatment with carvedilol (target dose 25 mg twice daily) and 1518 to metoprolol (metoprolol tartrate, target dose 50 mg twice daily). Patients were required to have chronic heart failure (NYHA II-IV), previous admission for a cardiovascular reason, an ejection fraction of less than 0.35, and to have been treated optimally with diuretics and angiotensin-converting enzyme inhibitors unless not tolerated. The primary endpoints were all-cause mortality and the composite endpoint of all-cause mortality or all-cause admission. Analysis was done by intention to treat.
  
  
  RESULTS
  The mean study duration was 58 months (SD 6). The mean ejection fraction was 0.26 (0.07) and the mean age 62 years (11). The all-cause mortality was 34% (512 of 1511) for carvedilol and 40% (600 of 1518) for metoprolol (hazard ratio 0.83 [95% CI 0.74-0.93], p=0.0017). The reduction of all-cause mortality was consistent across predefined subgroups. The composite endpoint of mortality or all-cause admission occurred in 1116 (74%) of 1511 on carvedilol and in 1160 (76%) of 1518 on metoprolol (0.94 [0.86-1.02], p=0.122). Incidence of side-effects and drug withdrawals did not differ by much between the two study groups.
  
  
  CONCLUSIONS
  Our results suggest that carvedilol extends survival compared with metoprolol.
authors.affiliation: National Heart and Lung Institute, Imperial College, London, UK. p.poole-wilson@imperial.ac.uk
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: Jacobus
authors.initials: J
authors.lastname: Lubsen
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: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: Armin
authors.initials: A
authors.lastname: Scherhag
authors.forename: Allan
authors.initials: A
authors.lastname: Skene
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D002423:Cause of Death; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006339:Heart Rate; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol