EFFICACY OF MIBEFRADIL COMPARED WITH AMLODIPINE IN SUPPRESSING EXERCISE-INDUCED AND DAILY SILENT ISCHEMIA - RESULTS OF A MULTICENTER, PLACEBO-CONTROLLED TRIAL

Background Mibefradil is a new benzimidazolyl-substituted tetraline-de rivative calcium antagonist. Its vasodilatory activity combined with a n ability to lower heart rate without negative inotropic effects as we ll as its long duration of action make it a promising anti-ischemic ag ent. Methods and Results Three hundred nine patients with coronary art ery disease, stable angina pectoris, and positive exercise tests were randomized to receive mibefradil (50, 100, or 150 mg), amlodipine (10 mg), or placebo. The anti-ischemic effects of mibefradil on exercise t est and silent ischemia parameters were assessed. At doses of 100 and 150 mg, mibefradil increased exercise duration (by 55.5 and 51.0 secon ds, respectively; P<.001 for both), increased time to onset of angina (by 98.3 and 82.7 seconds, respectively; P<.001), and increased time t o 1-mm ST depression (by 81.7 and 94.3 seconds, respectively; P<.001). By comparison, a 10 mg/d dose of amlodipine significantly improved on ly time to onset of angina (treatment effect: 38.5 seconds, P=.036). M ibefradil 100 mg and 150 mg decreased the number of episodes of silent ischemia (treatment effects: -3.1 and -3.6, respectively; P<.001) and the duration of silent ischemia (treatment effects: -9.2 minutes, P=. 048, and -14.6 minutes, P=.002, respectively). The decrease in the num ber of episodes of silent ischemia was also statistically significant in the group receiving 10 mg of amlodipine (-1.5; P=.036). Conclusions Once-daily doses of 100 and 150 mg mibefradil were effective in impro ving exercise tolerance and reducing ischemic episodes during ambulato ry monitoring in patients with coronary artery disease.