MIBEFRADIL IN THE TREATMENT OF CHRONIC STABLE ANGINA-PECTORIS - COMPARATIVE-STUDIES WITH OTHER CALCIUM-ANTAGONISTS

The ability of mibefradil, a new T-channel-selective calcium antagonis t, to improve exercise tolerance and silent ischemic parameters in pat ients with chronic stable angina was compared in 3 separate trials wit h 2 other commonly used calcium antagonists: diltiazem SR (120 mg/twic e daily) and amlodipine (10 mg/day). Compared with amlodipine, mibefra dil 100 mg given once daily over a 3-week period resulted in a statist ically significantly larger increase from baseline in total exercise t olerance test (ETT) duration (treatment difference of 40.9 sec, p = 0. 04), time to onset of angina (treatment difference 61.2 sec, p < 0.001 ), and time to onset of ischemia (treatment difference of 54.4 sec, p = 0.004). The decrease in weekly anginal episodes was 58% with mibefra dil versus 19% with amlodipine, and the reduction in nitroglycerin con sumption was 58% with mibefradil versus a 10% increase with amlodipine . The decrease in the number of silent ischemic episodes detected by a 48-hour Halter recording was significantly larger (p = 0.03) with mib efradil 100 mg (88%) compared with amlodipine 10 mg (38%). Similarly, a larger decrease in the duration of silent ischemia was observed with mibefradil (69%) compared with that seen with amlodipine (38%). The p reliminary results of a second trial comparing mibefradil with amlodip ine were consistent with the first demonstrating that the improvement for all 3 Err parameters was larger for mibefradil (ETT duration: 55.2 sec; delay in onset angina: 74.2 sec; time to onset of ischemia: 63.6 sec), but in this trial the treatment differences did not reach stati stical significance. In the trial comparing mibefradil (100 mg once da ily) with diltiazem SR (120 mg twice daily), both compounds had equiva lent effects on all ETT parameters tested. Mibefradil produced a 21% i ncrease in exercise duration compared with a 20% increase with diltiaz em. Although mibefradil yielded larger increases in the time to onset of angina and the time to onset of 1-mm ST-segment depression (42% and 38%, respectively) than did diltiazem (34% and 25%, respectively), th e treatment differences did not reach statistical significance. Both m ibefradil and diltiazem SR were associated with at least a 70% reducti on from baseline in anginal frequency and nitroglycerin consumption. M ibefradil-treated patients showed greater decreases in heart rate and the rate-pressure product at each stage of the Err than patients treat ed with amlodipine or diltiazem SR. All 3 drugs were well tolerated. H owever, compared with mibefradil, amlodipine and diltiazem SR produced a higher incidence of leg edema. In conclusion, the effectiveness of mibefradil in improving all 3 Err parameters was greater than that of amlodipine and equivalent to that of diltiazem SR. Moreover, mibefradi l provided greater reductions in the heart rate and cardiac workload t han did the other 2 drugs. (C) 1997 by Excerpta Medica, Inc.