EFFECTS OF THE NEW CALCIUM-ANTAGONIST MIBEFRADIL (RO-40-5967) ON EXERCISE DURATION IN PATIENTS WITH CHRONIC STABLE ANGINA-PECTORIS - A MULTICENTER, PLACEBO-CONTROLLED STUDY

Mibefradil (Ro 40-5967) is a novel calcium antagonist from a new chemi cal class and is the first that selectively blocks the T-type calcium channel. In this multicenter, double-blind, placebo-controlled, parall el designed study, its antianginal and antiischemic effects were evalu ated in 126 patients with chronic stable angina pectoris. Exercise tes ts were performed after 1 week of placebo (baseline) and 2 weeks after randomization to 25, 50, 100, and 150 mg (once daily) or placebo. Hig hly significant dose-response relations were present across all treatm ent groups for exercise duration, time to angina, and time to ST-segme nt depression. They were associated with a dose-dependent decrease in heart rate and blood pressure and plasma concentrations > 300 ng/ml. M ibefradil was well tolerated. First-degree atrioventricular black (8%) and dizziness (7%) were the most frequently reported adverse events; however, the first-degree atrioventricular block was dose-related, and only one patient discontinued the trial because of dizziness. The exc ellent efficacy and adequate safety profile of mibefradil may be a con sequence of T-type calcium-channel selectivity.