COMET: Carvedilol Or Metoprolol European Trial
Purpose
To compare the effects of carvedilol (a β1-, β2- and α1-receptor blocker) and short-acting metoprolol tartrate (a β1-receptor blocker) on clinical outcome in patients with chronic heart failure
Reference
Poole-Wilson PA, Swedberg K, Cleland JGF et al. for the COMET Investigators. 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. Lancet 2003;362:7–13.
COMET: Carvedilol Or Metoprolol European Trial - TRIAL DESIGN -
Design
Multicenter, multinational, randomized, double-blind, parallel group
Patients
3029 patients in NYHA class II–IV, previously hospitalized for a cardiovascular reason, who had left ventricular ejection fraction <0.35 and were receiving optimal treatment with diuretics and ACE inhibitors unless not tolerated
Follow up and primary endpoint
Primary endpoint: all-cause mortality. Mean 4.8 years follow up.
Treatment
Short-acting metoprolol tartrate titrated to target dose 50 mg twice daily or carvedilol titrated to target dose 25 mg twice daily
COMET: Carvedilol Or Metoprolol European Trial - TRIAL DESIGN continued-
Age (years)
a
Male
NYHA class
II
III
IV
Heart failure cause
Ischemic heart disease
Hypertension
Dilated
cardiomyopathy
Previous valve surgery
Left ventricular
ejection fraction
a
NT-proBNP
(
mg/L)b
Medications
Diuretics
ACE inhibitors
Angiotensin receptor
antagonists
Aldosterone
antagonists
Baseline characteristics (%)
62.3
80
49
47
4
54
18
44
2
Metoprolol tartrate
(n=1518)
61.6
79
48
48
3
51
18
44
3
Carvedilol
(n=1511)
a
Mean
b
Median
0.26
1185
99
91
7
11
Metoprolol tartrate
(n=1518)
0.26
1298
99
92
6
11
Carvedilol
(n=1511)
Poole-Wilson et al.
Lancet
2003;
362
:7–13.
COMET: Carvedilol Or Metoprolol European Trial - RESULTS -
All-cause mortality significantly reduced in carvedilol group compared with short-acting metoprolol tartrate (34 vs. 40%, P=0.0017)
Cardiovascular mortality significantly reduced (29 vs. 35%, P=0.0004)
No significant difference in composite secondary endpoint of all-cause mortality or admission (74 vs. 76%, hazard ratio 0.94, 95% CI 0.86–1.02, P=0.122):
Withdrawal rate identical (32%) and incidence of adverse events similar (94 vs. 96%) in both treatment groups
COMET: Carvedilol Or Metoprolol European Trial - RESULTS continued -
Years after randomization
Mortality
(%)
0
0
1
2
3
4
5
10
20
30
40
All-cause mortality
Poole-Wilson et al. Lancet 2003; 362:7–13.
COMET: Carvedilol Or Metoprolol European Trial - RESULTS continued -
P
All deaths
5 year Kaplan–Meier
Months at riska
Yearly mortality rate
Cardiovascular deaths
0.002
0.0004
All-cause mortality and cardiovascular death
Carvedilol
(n=1511)
600 (40%)
41.0%
45.2 (19.5)
10.0
534 (35%)
512 (34%)
35.3%
46.8 (18.9)
8.3
438 (29%)
0.83 (0.74–0.93)
0.80 (0.70–0.90)
Metoprolol tartrate
(n=1518)
Hazard ratio
(95% CI)
a
Mean (SD)
Poole-Wilson et al. Lancet 2003; 362:7–13.
COMET: Carvedilol Or Metoprolol European Trial - SUMMARY -
Compared with short-acting metoprolol tartrate, in patients with chronic heart failure carvedilol reduced:
All-cause mortality
Cardiovascular death
Whether COMET compared regimens that were equivalent in degree and duration of beta-blockade has been debated.a In COMET:
Reduction in resting heart rate and BP were significantly greater with carvedilol than metoprolol, suggesting under-dosing with metoprolol
Comparing metoprolol groups, mortality rate was higher and reduction in heart rate from baseline was lower than in MERIT-HF
COMET did not use the formulation and dose of metoprolol approved by authorities in CHF and used in MERIT-HF (200 mg metoprolol succinate CR/XL)
a See McMurray JV, Commentary on COMET, in Key Opinions, www.InCirculation.net 2003.