Twenty-four-hour activity of felodipine extended release in chronic stable angina pectoris

Abstract

To investigate the antiischemic efficacy and duration of action of the dihydropyridine calcium antagonist felodipine, 15 patients with stable exertional angina were enrolled in a double-blind, crossover study comparing 2 doses (5 and 10 mg) of felodipine extended release (ER) and placebo given once daily for 1 week. Bicycle exercise tests were repeated at the end of each treatment period 4 and 24 hours after dosing. Four hours after closing with both felodipine doses, only 5 patients discontinued the exercise test because of >2 mm of ST-segment depression, whereas 10 continued until exhaustion (p < 0.01 vs placebo). Compared with placebo, total exercise time was increased by 19% (p < 0.001), with no difference between doses. After 24 hours, exercise duration was prolonged up to physical exhaustion in 6 patients taking felodipine 10 mg (p < 0.05 vs both placebo and felodipine 5 mg); moreover, 11 patients taking 10 mg and 5 taking 5 mg increased time to 1 mm of ST depression ≥15% compared with exercise time during the placebo test. Mean time to 1 mm of ST depression at 24 hours was increased by 8% with 5 mg and by 18% with 10 mg (p < 0.001 vs placebo; p < 0.01 between doses). Total exercise time at 24 hours was increased with both doses (p < 0.001), with greater efficacy with the 10-mg dose (p < 0.05 vs 5 mg). This increased exercise tolerance may be attributed to a reduced afterload and increased myocardial oxygen supply: systolic blood pressure at rest was reduced (p < 0.005 vs placebo), and rate-pressure product at 1 mm of ST depression was increased (p < 0.02 vs placebo). In conclusion, a once-daily administration of felodipine ER provides antiischemic activity for 24 hours; the 5- and 10-mg doses are equally effective 4 hours after dosing, whereas the 10-mg dose is more efficacious at 24 hours. Because no differences in tolerability were observed, the 10-mg dose should be preferred for the once-daily treatment of chronic stable angina.