Acute effects on exercise tolerance of felodipine and diltiazem, alone and in combination, in stable effort angina

Abstract

The acute effects on exercise tolerance and electrocardiographic ischaemia of felodipine and diltiazem, alone or in combination, were investigated in 12 patients with documented stable effort-induced angina pectoris. After being withdrawn from their previous antianginal treatments, patients received a single oral dose of felodipine 10 mg, diltiazem 60 mg, their combination or placebo on four different days, according to a double-blind, 4 x 4 latin-square design. Exercise time to ischaemic threshold (ST-segment depression = 1 mm) and to peak exercise was significantly prolonged by the felodipine-diltiazem combination (492 and 504 s, respectively) against placebo (301 and 370 s, both P less than 0.01), felodipine alone (381 and 428 s, both P less than 0.01) and diltiazem alone (367 and 422 s, both P less than 0.01). The effects on total work followed a similar pattern. In comparison with placebo, the administration of felodipine and diltiazem alone significantly increased exercise duration as well as total work to ischaemic threshold and to peak exercise, with no differences between the two drugs. Systolic blood pressure during exercise was not affected by any of the treatments. However, in comparison with both placebo and diltiazem, the combination induced an increase (P less than 0.01) in heart rate during exercise. One patient suffered from symptomatic hypotension with the combination, and another had sinus tachycardia after felodipine. In conclusion, the acute concomitant administration of felodipine and diltiazem in patients with stable effort angina induces a marked improvement in exercise tolerance in comparison with placebo, felodipine alone and diltiazem alone. However, the benefit/risk profile of such a combination requires further, long-term investigation.