2003, Carvedilol vs Metoprolol in Heart Failure, The Lancet
The COMET trial randomized 3029 patients with NYHA Class II, III or IV heart failure and a reduced ejection fraction of 35% or less to receive either 25mg of carvedilol twice daily or 50mg of metoprolol twice daily on top of optimal therapy with diuretics and ACE inhibitors unless not tolerated. The co-primary endpoints were all-cause mortality and a composite of all-cause death or all-cause hospitalization.
Patients were followed for 5 years. Overall, 35% of patients assigned to the carvedilol group and 40% in the metoprolol group died (HR:0.83; 95%CI: 0.74 to 0.93; p=0.0017). This reduction in mortality was consistent across all pre-specified subgroups, including: sex, age, NYHA class, LVEF, heart rate, systolic blood pressure, or diabetic status. The co-primary composite endpoint occurred in 75% of patients in the carvedilol group and 74% of those in the metoprolol group (HR: 0.94; 95%CI: 0.86 to 1.02; p=0.122).