COMET Trial Carvedilol Or Metoprolol European Trial Presented

COMET Trial Carvedilol Or Metoprolol European Trial Presented at European Heart Failure Meeting 2003

COMET Trial 3, 029 patients with Class III-IV heart failure Enrolled at 317 centers in 15 European countries Carvedilol (target dose 25 mg twice daily) § A multiple adrenergic inhibitor (n = 1, 511) Metoprolol tartrate (target dose 50 mg twice daily) § A beta-1 blockade agent (n = 1, 518) Endpoints (mean follow-up 58 months): g g Primary – 1) All-cause mortality and 2) All-cause mortality or all-cause hospitalization Secondary – Composite of all cause mortality or cardiovascular hospitalization; Composite of cardiovascular death, non-fatal acute MI, or heart transplantation; Worsening of heart failure; Cardiovascular death; NYHA class European Heart Failure Meeting 2003

COMET Trial: Primary Endpoint Analysis All-cause mortality HR 0. 83 95% CI 0. 74 -0. 93 p=0. 0017 European Heart Failure Meeting 2003

COMET Trial: Primary Endpoint Analysis All-cause mortality or all-cause hospitalization HR 0. 93 95% CI 0. 86 -1. 10 p=0. 1222 European Heart Failure Meeting 2003

COMET: Dosing Issues Metoprolol Succinate Metoprolol Tartrate Metoprolol-Tartrate (immediate release) COMET Target dose: 2 x 50 mg tartrate ~78 mg Metoprolol-Succinate (CR/XR) MERIT-HF Target dose: 1 x 190 mg succinate ~155 mg Metoprolol (achieved mean dose in MERIT-HF ~130 mg) Slide Provided by: Dr. med. M. Elsner, Medizinische Klinik I, St. Josefs Hospital, Solmsstr. 15, 65189, Wiesbaden, Germany, Tel. /Fax: +49 -611 -177 -1205. Dr. Elsner has no conflict of interest to declare.

COMET Trial: Summary • First randomized morality trial to compare 2 beta-blockers in patients with CHF • Treatment with carvedilol was associated with rate of all-cause mortality (primary endpoint) but was not associated with difference in co-primary endpoint of all-cause mortality or all-cause hospitalization in patients with CHF • Trial used immediate-release formulation of metoprolol tartrate not controlled-release formulation of metoprolol succinate used in MERIT HF trial, the main trial showing a benefit of metoprolol compared with placebo in heart failure patients