Optimal control of myocardial ischaemia: the benefit of a fixed combination of atenolol and nifedipine in patients with chronic stable angina.

OBJECTIVE To study the effects on myocardial ischaemia of 50 mg of atenolol, 20 mg of slow release nifedipine, and their fixed combination given 12 hourly. DESIGN A treadmill exercise test and 24 hour ambulatory electrocardiographic monitoring were carried out after a period of five days off treatment (control) and at the end of three weeks of each treatment period. PATIENTS 23 patients with stable angina pectoris, documented coronary artery disease, and a positive exercise test were randomised in a double blind, three way, cross over study. RESULTS Compared with the control, nifedipine significantly induced an increase in resting heart rate of (mean (SEM)) 14 (2) beats/min whereas atenolol and the combination significantly reduced it by 24 (2) and 20 (1) beats/min respectively. The number of exercise tests rendered negative after each intervention was five for nifedipine, nine for atenolol, and 11 for the combination. Compared with the control the time to the start of myocardial ischaemia (1 mm ST segment depression) during exercise significantly increased by 3.2 (0.6) min after nifedipine, by 4.6 (0.4) min after atenolol, and by 4.6 (0.5) min after the combination; rate-pressure product (beats/min. mm Hg) at 1 mm ST segment depression increased by 2824 (970) after nifedipine but fell by 4436 (900) and 4501 (719) after atenolol and the combination. The weekly frequency of angina was reduced from a mean of five while taking nifedipine, to three while taking atenolol, and to two while taking the combination. The total ischaemic time during ambulatory monitoring was significantly reduced from 69 (17) min during control to 37.5 (9.8) min during nifedipine, to 15.6 (5.5) min during atenolol, and to 6.5 (2.7) min during the combination. CONCLUSION The undesirable effect of a high basal heart rate induced by nifedipine was neutralised by its combination with atenolol. Whereas atenolol and the combination were equally efficacious in controlling exercise induced ischaemia, the combination was more effective in reducing total ischaemic burden.