Carvedilol protects better against vascular events than metoprolol in heart failure: results from COMET.
OBJECTIVE
We explored whether vascular protection by carvedilol could contribute to its superior effects in the treatment of heart failure (HF) compared with metoprolol tartrate in the COMET (Carvedilol Or Metoprolol European Trial) study.


BACKGROUND
Full adrenergic blockade by carvedilol and additional (e.g., antioxidative) properties may lead to vascular protection relative to beta-1 blockade alone, and contribute to its efficacy in HF treatment.


METHODS
Three thousand twenty-nine patients with HF due to ischemic (51%) or idiopathic cardiomyopathy (44%) were randomized double-blind to carvedilol (n = 1,511) or metoprolol (n = 1,518) and followed for 58 months. Vascular end points were cardiovascular death, stroke, stroke death, myocardial infarction (MI), and unstable angina.


RESULTS
The effect of carvedilol on cardiovascular death improved consistently in subgroups with prespecified baseline variables. Myocardial infarctions were reported in 69 carvedilol and 94 metoprolol patients (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52 to 0.97, p = 0.03). Cardiovascular death or nonfatal MI combined were reduced by 19% in carvedilol (HR 0.81, 95% CI 0.72 to 0.92, p = 0.0009 vs. metoprolol). Unstable angina was reported as an adverse event in 56 carvedilol and in 77 metoprolol patients (HR 0.71, 95% CI 0.501 to 0.998, p = 0.049). A stroke occurred in 65 carvedilol and 80 metoprolol patients (HR 0.79, 95% CI 0.57 to 1.10). Stroke or MI combined occurred in 130 carvedilol and 168 metoprolol patients (HR 0.75, 95% CI 0.60 to 0.95, p = 0.015), and fatal MI or fatal stroke occurred in 34 carvedilol and in 72 metoprolol patients (HR 0.46, 95% CI 0.31 to 0.69, p = 0.0002). Death after a nonfatal MI or stroke occurred in 61 of 124 carvedilol and in 106 of 160 metoprolol patients (HR 0.66, 95% CI 0.48 to 0.90, p = 0.0086).


CONCLUSIONS
Carvedilol improves vascular outcomes better than metoprolol. These results suggest a ubiquitous protective effect of carvedilol against major vascular events.
Remme
Willem J
WJ
Sticares Cardiovascular Research Institute, Rhoon, The Netherlands. w.j.remme@sticares.org
Torp-Pedersen
Christian
C
Cleland
John G F
JG
Poole-Wilson
Philip A
PA
Metra
Marco
M
Komajda
Michel
M
Swedberg
Karl
K
Di Lenarda
Andrea
A
Spark
Phillip
P
Scherhag
Armin
A
Moullet
Christine
C
Lukas
Mary Ann
MA
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000789:Angina, Unstable / Q000209:etiology / Q000517:prevention & control; 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*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D011412:Propanolamines / Q000627:therapeutic use*; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D016019:Survival Analysis; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol