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 c oronary 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 rang e, 120 to 480 mg) was established to determine optimal, individual dos ages of slow-release verapamil in 44 patients with stable intermittent claudication (Fontaine classification stage II) with respect to walki ng capacity. A randomized, double-blind, placebo-controlled, crossover study (4 weeks) was performed to assess clinical and hemodynamic effe cts of verapamil. The optimal daily dose of verapamil on maximal walki ng ability was 120 (8 patients), 240 (8 patients), 360 (14 patients), and 480 mg (14 patients). Walking distances were measured at a metrono me-controlled speed of 60 steps per minute on level surface. Optimal i ndividual 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 i nitial systolic ankle pressure (r=.49, P<.001) and ankle/brachial pres sure index (r=.37, P<.013). Verapamil had no effect on systolic ankle pressure, ankle/brachial pressure index, peripheral leg temperature, o r blood pressure, which suggests that the drug may have extrahemodynam ic effects, possibly brought about through improved oxygen metabolism. Conclusions Verapamil showed significant clinical benefits in patient s with moderate intermittent claudication in this short term study. In dividual optimization of drug dosage should be considered an option bo th in trials and in the clinical setting in these patients.