Effects of new calcium antagonist, mibefradil (Ro 40–5967), on silent ischemi in patients with stable chronic angin pectoris: multicenter placebo-controlled study

Objectives. The purpose of this study was to evaluate the effects of mibefradil (Ro 40–5967) on the frequency and duration of episodes of asymptomatic ischemi in patients with stable angin pectoris and to determine the most efficient single therapeutic dose of this drug. Background. Mibefradil is novel calcium channel antagonist that shows high bioavailability, induces no reflex tachycardi and has no negative inotropic effects. Methods. In multicenter, double-blind, placebo-controlled, parallel-design trial, 126 patients with chronic stable angin pectoris were studied. After 1 week of placebo run-in period, patients were randomized to receive 25, 50, 100, 150 mg of mibefradil or placebo for 2 weeks. Ambulatory 48-h electrocardiographic (ECG) monitoring was performed at the end of both the placebo run-in period and the active treatment period. Results. Compared with placebo, mibefradil was associated with significantly less ischemi as manifested during ambulatory ECG monitoring. In the 150- and 100-mg groups, respectively, the drug resulted in 73% and 63% reduction in the frequency of episodes of ST segment depression and 78% and 58% reduction in the total duration of ST segment depression. Highly significant linear dose-response relations were present across all treatment groups for ischemic episodes and ischemi duration (p < 0.001). Electrocardiographic abnormalities related to treatment were first-degree atrioventricular block, sinus bradycardi and short Wenckebach episodes, observed during sleep on Holter monitoring. All ECG events were dose related. Conclusions. Mibefradil is new, safe, well tolerated and very effective dose-dependent anti-ischemic calcium channel antagonist.