ADDING THE NEW CALCIUM-ANTAGONIST MIBEFRADIL TO PATIENTS RECEIVING LONG-TERM BETA-BLOCKER THERAPY RESULTS IN IMPROVED ANTIANGINAL AND ANTIISCHEMIC EFFICACY

Objective The objective of this study was to evaluate the efficacy, to lerability, and safety of mibefradil, a new selective T-type calcium c hannel blocker, in patients with chronic stable angina pectoris receiv ing concomitant beta-blocker therapy. Design This was a multicenter, d ouble-blind, placebo-controlled study. Methods Ninety-five patients re ceiving a stable dose of beta-blockers, which was not changed For the purpose of the study, were administered either 50 mg mibefradil once d aily for 2 weeks, then 100 mg once daily for 2 weeks, or matching plac ebo. Efficacy was evaluated by treadmill exercise tolerance testing 24 hours after dose and by diary registration of anginal episodes and ni troglycerin consumption. Results Two weeks of treatment with 50 mg mib efradil resulted in a significant increase in symptom-limited exercise duration and a significant delay in the onset of persistent 1 mm ST-s egment depression (placebo-corrected treatment effect: 23.2 and 51.7 s econds, respectively). Treatment with the 100 mg dose for 2 additional weeks resulted in a larger improvement in treadmill exercise toleranc e testing duration and onset of ischemia (placebo-corrected treatment effect: 52.7 and 75.8 seconds, respectively). In addition, a significa nt decrease in weekly anginal episodes was observed with the 100 mg do se of mibefradil compared with the effect in the placebo group (-53% v s -12%, p = 0.037). Conclusions The combined treatment of mibefradil a nd beta-blockers was well tolerated, and the overall incidence of adve rse events was no different from that with beta-blockers alone. The re sults indicate that adding mibefradil to chronic beta-blocker treatmen t is associated with significant improvement in efficacy, which is not achieved at the expense of tolerability.