The effect of mibefradil on ischemic episodes with and without increase inheart rate

Myocardial ischemia during daily life can be induced by increased demand an d by increased coronary tone. The purpose of this study was to assess the m echanism 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 r un-in period patients received 50 mg, 100 mg, or 150 mg of mibefradil per d ay and repeat 48 hours AEM was performed. Ischemic episodes were divided in to 2 categories: Type I is those in which an increase in heart rate > 10% p receded the development of 1 mm ST depression; Type II is those with less t han or equal to 10% increase in heart rate. Of the 625 ischemic episodes re corded at baseline, 83% were Type I and 17% were Type II. At 50 mg mibefrad il 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 preven ting 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 in creased coronary tone.