OBJECTIVE: To describe the pharmacology, pharmacokinetics, and

clinical efficacy of mibefradil compared with other agents used for hypertension and angina. DATA SOURCES: A MEDLINE search was performed for the period of January 1980 through September 1997 using the key terms mibefradil or Ro 40-5967. All articles written in English were considered for review. STUDY SELECTION AND DATA EXTRACTION: All clinical studies involving mibefradil were evaluated. Preclinical data were included if these data were not adequately represented in clinical (human) studies. DATA SYNTHESIS: Mibefradil is the first member of a new class of calcium-channel antagonists (CCAs) that block the T-type calcium channels. A long elimination half-life makes once-daily dosing feasible, and the drug’s lack of negative inotropy and reflex tachycardia distinguishes it from other available CCAs. When administered at recommended dosages (50 or 100 mg once daily), mibefradil reduces blood pressure over 24 hours in patients with hypertension, improves exercise capacity, and relieves anginal symptoms in patients with chronic stable angina pectoris. CONCLUSIONS: Clinical studies have found that the antihypertensive effects of mibefradil are comparable with those of nifedipine, verapamil, and amlodipine, and more effective than those of diltiazem. These effects result from peripheral vasodilation and a slight reduction in heart rate. Selective vasodilation of the coronary vasculature makes it an effective antianginal agent when used alone or added to β-blocker therapy. Mibefradil demonstrates no significant effects on cardiac contractility, and no adrenergic stimulation resulting in reflex tachycardia. Therefore, it may have some advantages over currently available CCAs, especially in patients with congestive heart failure, although such advantages are unproven in published clinical trials. Ongoing clinical studies, including the Mortality Assessment in Congestive Heart Failure Trial (MACH-1) currently in progress, are needed to clarify mibefradil’s place in cardiovascular therapy. KEY WORDS: mibefradil, calcium-channel antagonist, hypertension, angina