Comparative effects of prolonged therapy with four calcium ion antagonists (diltiazem,nicardipine, tiapamil and verapamil) in patients with chronic stable angina pectoris

Summary The comparative effects of prolonged chronic therapy with diltiazem, nicardipine, tiapamil and verapamil on exercise tolerance, ST-segment changes and heart rate were examined in 63 patients with established chronic stable angina pectoris. Multistage computer-assisted symptom-limited tread-mill exercise tests were performed after 2 weeks of placebo (baseline) and then after 4 months of open-label chronic drug therapy. Diltiazem improved the exercise duration by 95% (p<0.001), nicardipine by 45% (p<0.001), tiapamil by 69% and verapamil by 79% (p<0.001). Maximal ST-segment depression was not altered by any of the drugs, but time to the development of 1 mm ST-segment depression was significantly improved in all cases. Diltiazem and verapamil reduced the heart rate at rest significantly by 6 and 8 beats/minute, respectively, whereas nicardipine increased it by 10 beats/minute (p<0.02), and tiapamil did not produce any significant change. Maximal heart rate at the peak of exercise was increased by 14% with nicardipine (p<0.001) and 6% with verapamil (p<0.05), whereas diltiazem and tiapamil did not produce any appreciable effect. The rate-pressure product at the peak of exercise remained unaltered with diltiazem, tiapamil and verapamil, but with nicardipine it increased significantly to 222±10 units from a baseline of 175±6 units with placebo. During diltiazem treatment, 1 patient died of myocardial infarction after 8 weeks of therapy. During tiapamil, 2 patients were withdrawn after 10 weeks because they developed unstable angina. During verapamil therapy, 4 patients were withdrawn; 1 developed myocardial infarction after 4 weeks, 2 patients developed worsening angina and 1 patient showed prolongation of the PR interval after 8 weeks of treatment. Constipation was reported by 7 patients during verapamil therapy. During nicardipine treatment one patient reported pedaloedema and dyspnoea after 16 weeks and was withdrawn. At the dosages used, all 4 calcium ion antagonists studied have been shown to be effective antianginal agents during long-term therapy, but differing effects on heart rate and rate-pressure product suggest that they do not have a similar mechanism of action.