Effect of verapamil in intermittent claudication - A randomized, double-blind, placebo-controlled, cross-over study after individual dose-response assessment

Background The calcium antagonist verapamil is a vasodilator drug that has been shown to increase oxygen extraction of ischemic tissues in coronary and peripheral vascular disease. Methods and Results Since the balance between the positive and the negative effects of vasodilation may be delicate in ischemic diseases a dose-response study (dose range, 120 to 480 mg) was established to determine optimal, individual dosages of slow-release verapamil in 44 patients with stable intermittent claudication (Fontaine classification stage II) with respect to walking capacity. A randomized, double-blind, placebo-controlled, crossover study (4 weeks) was performed to assess clinical and hemodynamic effects of verapamil. The optimal daily dose of verapamil on maximal walking ability was 120 (8 patients), 240 (8 patients), 360 (14 patients), and 480 mg (14 patients). Walking distances were measured at a metronome-controlled speed of 60 steps per minute on level surface. Optimal individual doses of verapamil increased mean pain-free walking distance by 29% from 44.9 to 57.8 meters (P<.01) and maximal walking distance by 49% from 100.7 to 149.8 meters (P<.001) compared with placebo. The increase in maximal walking distance correlated positively only with initial systolic ankle pressure (r=.49, P<.001) and ankle/brachial pressure index (r=.37, P<.013). Verapamil had no effect on systolic ankle pressure, ankle/brachial pressure index, peripheral leg temperature, or blood pressure, which suggests that the drug may have extrahemodynamic effects, possibly brought about through improved oxygen metabolism. Conclusions Verapamil showed significant clinical benefits in patients with moderate intermittent claudication in this short term study. Individual optimization of drug dosage should be considered an option both in trials and in the clinical setting in these patients.