title: The effect of mibefradil on ischemic episodes with and without increase in heart rate.
abstract: 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 < or = 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.
authors: Jesselson Heart Center, Shaare Zedek Medical Center, Jerusalem, Isreal. cardio@szmc.org.il
authors: D
authors: D
authors: Tzivoni
authors: Z
authors: Z
authors: Gilula
authors: M W
authors: MW
authors: Klutstein
authors: L
authors: L
authors: Reisin
authors: S
authors: S
authors: Botvin
authors: I
authors: I
authors: Kobrin
mesh_terms: D000787:Angina Pectoris / Q000150:complications; D018660:Blood Pressure Monitoring, Ambulatory; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D020748:Mibefradil / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000145:classification / Q000150:complications / Q000188:drug therapy*
chemical_list: D002121:Calcium Channel Blockers; D020748:Mibefradil