Effects of a new calcium antagonist, mibefradil (Ro 40-5967), on silent ischemia in patients with stable chronic angina pectoris: a multicenter placebo-controlled study. The Mibefradil International Study Group.
OBJECTIVE
The purpose of this study was to evaluate the effects of mibefradil (Ro 40-5967) on the frequency and duration of episodes of asymptomatic ischemia in patients with stable angina pectoris and to determine the most efficient single therapeutic dose of this drug.


BACKGROUND
Mibefradil is a novel calcium channel antagonist that shows a high bioavailability, induces no reflex tachycardia and has no negative inotropic effects.


METHODS
In a multicenter, double-blind, placebo-controlled, parallel-design trial, 126 patients with chronic stable angina pectoris were studied. After 1 week of a 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 ischemia as manifested during ambulatory ECG monitoring. In the 150- and 100-mg groups, respectively, the drug resulted in a 73% and 63% reduction in the frequency of episodes of ST segment depression and a 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 ischemia duration (p < 0.001). Electrocardiographic abnormalities related to treatment were first-degree atrioventricular block, sinus bradycardia and short Wenckebach episodes, observed during sleep on Holter monitoring. All ECG events were dose related.


CONCLUSIONS
Mibefradil is a new, safe, well tolerated and very effective dose-dependent anti-ischemic calcium channel antagonist.
Braun
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Department of Cardiology, Tel-Aviv Medical Center, Tel Aviv, Israel.
van der Wall
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Emanuelsson
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Kobrin
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D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015716:Electrocardiography, Ambulatory; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D020748:Mibefradil; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000517:prevention & control*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D020748:Mibefradil