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

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      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.
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