Felodipine versus placebo in stable effort-induced angina pectoris in patients inadequately controlled with metoprolol--a dose-finding study.

We compared the antianginal and antiischaemic effect and tolerability of four different doses of felodipine extended-release (ER) tablets with placebo in patients with stable effort-induced angina pectoris treated with beta-blocker [metoprolol controlled release (CR) 100 mg once daily, o.d.]. Seventy-five patients were enrolled in the study. At the end of a 2-week single-blind period, all patients performed two exercise tests. If total exercise time did not vary by > 15% between the two tests and both tests were limited by anginal discomfort and concomitant ST depression of at least 1 mm, the patients were randomized to double-blind treatment (66 patients). Each patient received three of the following treatments: felodipine 2.5, 5, 10, or 20 mg, or placebo. The treatments were given o.d. in a cross-over, balanced incomplete block design with three of 3-week treatment periods. Exercise tests were performed 12 and 24 h after dose intake at the end of each treatment period. Fifty-nine patients completed the study. Twelve hours after dose administration, 10 and 20 mg felodipine increased time to onset of anginal pain by 60 and 63 s on the average, respectively, as compared with placebo (p = 0.001). Time to 1-mm ST depression was prolonged by 29 s after 10 mg (p = 0.14) and by 30 s after 20 mg (p = 0.13) felodipine. Time to end of exercise was increased by 28 s (p = 0.07) and 15 s (p > 0.20), respectively. Twenty-four hours after dose, time to onset of angina was 32 (p = 0.09) and 36 s (p = 0.05) longer after 10 and 20 mg felodipine, respectively, than after placebo. Times to 1-mm ST depression and end of exercise were similar to those after placebo. Twelve hours after dose, pain score and ST depression at highest comparable workload were significantly lower in patients receiving felodipine 10 and 20 mg than in those receiving placebo. After 12 h, rate-pressure product (RPP) at highest comparable workload was significantly lower in patients receiving felodipine 20 mg than in those receiving placebo. Felodipine 2.5 and 5 mg had no statistically significant antianginal or antiischemic effects. Felodipine ER 10 and 20 mg o.d. for 3 weeks had antianginal and antiischemic effects lasting at least 12 h after dose administration in patients with angina pectoris who received chronic treatment with metoprolol CR. Felodipine ER 10 mg was as effective as 20 mg. Felodipine appeared to be safe and was generally well tolerated.