The COMET Trial : Carvedilol vs immediate release metoprolol

ProfJameson Landmark Decisions Leave a comment  

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The Headline

Patients with CHF taking carvedilol have significantly less mortatility than patients taking metoprolol

 

The Facts

The Big Idea:
This study looked to show which beta-blocker was superior, carvedilol or metoprolol.

Study Design:
Multicenter (341 centers in 15 European countries), randomized, double blind, parallel-group

Outcomes
All cause mortatility and all cause mortatility and all cause admission

Number of Patients
3029 randomized: 1511 in carvedilol arm and 1518 in metoprolol arm

Type of Patients
Symptomatic heart failure (NYHA Class II-IV), one cardio admission in past 2 years, being treated with ACEI’s and diuretics unless contraindications, LVEF of < or = 0.35 withink previous 3 months.

Important ExclusionsRecent change in therapy or recent use of beta or alpha blockers in past 2 weeks; being treated with CCBs, amiodarone, class-I antiarrhythmics or investigational drugs in past 30 days; patients with MI, unstable angina or stroke in last 2 months; uncontrolled HTN (>170/105); pregnancy; autmatic defibrillator, known drug or alcohol issues

Interventions
3.125 mg carvedilol BID or 5 mg metoprolol tartrate BID (both titrated up to goals of 25 mg carvedilol and 50 mg BID metoprolol tartrate)

Duration
58 Months

Statistics
Cox’s proportional hazard, log rank test

Funding

Roche and GlaxoSmithKline

Results

All cause mortality: Carvedilol – 34%; Metoprolol – 40% (HR 0.83 [0.74 - 0.93] p = 0.002) All cause mortality and all cause admission: Carvedilol – 74%; Metoprolol – 76% (HR 0.94 [0.86 - 1.02] p = 0.122) For the Cynic
Once major concern with this study was the use of metoprolol tartrate when compared to carvedilol. The extended release succincate salt is most often used and studied in CHF. It is possible the results may have changed someone based on the different drug formulations. Also some of the funding comes from Roche – who makes carvedilol (Coreg). Whether the formulation of metoprolol succinate would fare better, is an interesting question. Another interesting question is whethere the alpha action from the carvedilol contributes to its increased efficacy.

Carvedilol shows increased benefit in CHF patients compared to metoprolol tartrate.

Reference

Poole-Wilson PA, Swedberg K, Cleland JGF, et al. 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 Jul 5; 362: 7-13

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