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Myocardial ischemia during daily life can be induced by increased demand and by increased coronary tone. The purpose of this study was to assess the mechanism of action of mibefradil, a new T-channel calcium blocker that is a vasodilator with negative chronotropic properties. Included in this study were 114 patients with chronic stable angina pectoris and ischemic episodes during baseline 48-hour ambulatory ECG monitoring (AEM). After a placebo run-in period patients received 50 mg, 100 mg, or 150 mg of mibefradil per day and repeat 48 hours AEM was performed. Ischemic episodes were divided into 2 categories: Type I is those in which an increase in heart rate >10% preceded the development of 1 mm ST depression; Type II is those with ≤10% increase in heart rate. Of the 625 ischemic episodes recorded at baseline, 83% were Type I and 17% were Type II. At 50 mg mibefradil dose, there was a significant decrease in the number of Type I ischemic episodes but not of Type II. At doses of 100 mg and 150 mg/day, there was a significant decrease in frequency of both Types of ischemic episodes. At a low dose of 50 mg/day, mibefradil reduces ischemia predominantly by preventing an increase in heart rate, while at higher doses of 100 mg and 150 mg/day, it also acted as a vasodilator suppressing episodes associated with increased coronary tone. |
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