FELODIPINE VERSUS PLACEBO IN STABLE EFFORT-INDUCED ANGINA-PECTORIS INPATIENTS 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 wi th placebo in patients with stable effort-induced angina pectoris trea ted 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 exerc ise tests. If total exercise time did not vary by > 15% between the tw o tests and both tests were limited by anginal discomfort and concomit ant ST depression of at least 1 mm, the patients were randomized to do uble-blind treatment (66 patients). Each patient received three of the following treatments: felodipine 2.5, 5, 10, or 20 mg, or placebo. Th e treatments were given o.d. in a cross-over, balanced incomplete bloc k design with three of 3-week treatment periods. Exercise tests were p erformed 12 and 24 h after dose intake at the end of each treatment pe riod. Fifty-nine patients completed the study. Twelve hours after dose administration, 10 and 20 mg felodipine increased time to onset of an ginal pain by 60 and 63 s on the average, respectively, as compared wi th 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) felodipin e. 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 o f 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 depr ession 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 p roduct (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 o r antiischemic effects. Felodipine ER 10 and 20 mg o.d. for 3 weeks ha d antianginal and antiischemic effects lasting at least 12 h after dos e 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 tolerate d.