Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure--COMET.
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.
Torp-Pedersen
Christian
C
Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark. ctp@heart.dk
Poole-Wilson
Philip A
PA
Swedberg
Karl
K
Cleland
John G F
JG
Di Lenarda
Andrea
A
Hanrath
Peter
P
Komajda
Michel
M
Lutiger
Beatrix
B
Metra
Marco
M
Remme
Willem J
WJ
Scherhag
Armin
A
Skene
Allan
A
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
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol