ANTIANGINAL AND ANTIISCHEMIC EFFICACY OF NICORANDIL COMPARED WITH NIFEDIPINE IN PATIENTS WITH ANGINA-PECTORIS AND CORONARY HEART-DISEASE - A DOUBLE-BLIND, RANDOMIZED, MULTICENTER STUDY

Patients with stable, effort-induced angina pectoris and a typical combination of anginal pain and ischemic ST depression in exercise tolerance tests were randomized to treatment for 8 weeks with nicorandil (a newly developed antianginal and anti-ischemic drug) or nifedipine. After 4 weeks, the dosage of nicorandil was increased from 10 mg b.i.d. to 20 mg b.i.d., but the recommended dosage of nifedipine, 20 mg b.i.d., was kept constant during the study period. Double-blind treatment was preceded by a 2-week prephase during which patients were treated with isosorbide dinitrate. During the study period, patients were asked to report the rate of anginal attacks and consumption of sublingual nitroglycerin. Measurements of blood pressure and heart rate at rest and during exercise always were performed 2 h after drug intake. Fifty-eight patients were randomized-29 to nicorandil and 29 to nifedipine. There were large individual variations in anginal attack rates, which makes group comparisons difficult, but in the nicorandil group, the anginal attack rate decreased significantly compared with baseline frequency. Systolic blood pressure at rest was reduced significantly only with the highest dose of nicorandil, but nifedipine had a significant effect on both systolic and diastolic blood pressures as well as on the heart rate. Both treatments significantly increased exercise duration, time to onset of angina pectoris, and time to 1-mm ST depression. In the nicorandil group, an improvement was noted with the 20-mg dose compared with the 10-mg dose, but no significant differences were noted between the nicorandil and nifedipine groups after either 4 or 8 weeks of treatment. During the double-blind treatment. there were four dropouts in the nicorandil group (one because of palpitation and fatigue, one because of myocardial infarction, and two because of headache) and three dropouts in the nifedipine group (one because of atrial fibrillation, one because of tachycardia and vertigo, and one because of noncompliance). The most common adverse effect reported in both groups was headache of mild-to-moderate intensity. Symptoms caused by peripheral vasodilatation were commonly reported in the nifedipine group. Thus, both drugs caused significant and clinically relevant improvement in exercise test variables. A more pronounced effect on peripheral vasodilatation with nifedipine compared with nicorandil was reflected by a more marked effect on resting hemodynamics and a higher frequency of vasodilator side effects in the nifedipine group.