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(Circulation. 1997;96:2557-2564.)
© 1997 American Heart Association, Inc.

Articles

Efficacy of Mibefradil Compared With Amlodipine in Suppressing Exercise-Induced and Daily Silent Ischemia

Results of a Multicenter, Placebo-Controlled Trial

Dan Tzivoni, MD; Honer Kadr, MD; Simon Braat, MD; Wolfgang Rutsch, MD; José Antonio Ramires, MD; ; Isaac Kobrin, MD

From the Shaare Zedek Medical Center (D.T.), Jerusalem, Israel; Oldchurch Hospital (H.K.), Romford, UK; Academisch Ziekenhuis (S.B.), The Netherlands; Univ. Klinik Rudolf Virchow (W.R.), Berlin, Germany; Instituto de Corado (J.A.R.), Sao Paulo, Brazil; and Hoffmann–La Roche (I.K.), Nutley, NJ.

Correspondence to Dan Tzivoni, MD, Professor of Medicine/Cardiology, Director, Department of Cardiology, Jesselson Heart Center, Shaare Zedek Medical Center, POB 3235, Jerusalem, 91031 Israel.

Background Mibefradil is a new benzimidazolyl-substituted tetraline-derivative calcium antagonist. Its vasodilatory activity combined with an ability to lower heart rate without negative inotropic effects as well as its long duration of action make it a promising anti-ischemic agent.

Methods and Results Three hundred nine patients with coronary artery 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 test and silent ischemia parameters were assessed. At doses of 100 and 150 mg, mibefradil increased exercise duration (by 55.5 and 51.0 seconds, respectively; P<.001 for both), increased time to onset of angina (by 98.3 and 82.7 seconds, respectively; P<.001), and increased time to 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 only time to onset of angina (treatment effect: 38.5 seconds, P=.036). Mibefradil 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 number 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 improving exercise tolerance and reducing ischemic episodes during ambulatory monitoring in patients with coronary artery disease.

Key Words: mibefradil • coronary artery disease • ischemia • amlodipine • exercise • electrocardiography, ambulatory

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