Comparison of safety and efficacy of carvedilol and metoprolol in stable angina pectoris

Abstract

In a double-blind, randomized, 3-month multicenter study, the safety and tolerability and the antianginal and anti-ischemic efficacy of carvedilol 25 to 50 mg twice daily were assessed in comparison with metoprolol 50 to 100 mg twice daily in younger and elderly patients with stable angina. After a 7-day placebo run-in at the end of which a symptom-limited bicycle ergometric exercise was performed, 368 patients were randomly allocated to the parallel treatment groups. After 4 weeks of therapy with a low dose, a further exercise test was performed and patients were titrated in single-blind fashion to the higher dose if the increase in total exercise time was <1 minute, and there was no safety concern. After a further 8 weeks of treatment a third exercise test was performed. Carvedilol low dose/high dose was shown to be at least as safe and well tolerated as metoprolol low dose/high dose both in younger and elderly patients. There were no hitherto unknown adverse events and no marked change in the types of events after increase of the doses. Early adverse events after treatment initiation or uptitration were equal with both medications, indicating no particular risk associated with carvedilol’s vasodilatory action. No rebound phenomena were observed. Both drugs showed good antianginal and anti-ischemic efficacy, with marked increases on uptitration including patients ≥65 years of age. However, in the doses selected, which appeared equipotent with respect to β blockade, carvedilol’s improvement of time to 1-mm ST-segment depression was statistically significantly greater than that of metoprolol. This could be due to its additional vasodilatory or antioxidative actions. Based on the safety and efficacy data of the present study, use of the higher of the 2 recommended doses of carvedilol and metoprolol appears justified in younger and elderly patients without adequate therapeutic control at lower doses.