Long-Term Effects of Ticlopidine on Lower Limb Blood Flow, Ankle/Brachial Index and Symptoms in Peripheral Arteriosclerosis

The aim was to test within a randomized double-blind trial whether the platelet inhibitor ticlopidine might improve peripheral blood flow and distal pressures in patients with aortofemoral arteriosclerosis. One hundred and one patients with intermittent claudication were studied after one year, after two to three years, and after five years of treatment with ticlopidine, 500 mg/day, or placebo. Analysis was performed according to years on treatment. Baseline flow values as assessed by venous occlusion plethysmography were significantly and similarly deranged in the ticlopidine and placebo groups as compared with a reference group of healthy subjects. Ankle/brachial index was unrelated to either leg blood flow variables or walking distance. After five years of treatment (median follow-up time) a slight tendency to a slower progression of disease was observed in the ticlopidine group as compared with placebo. However, intergroup differences were not significant. Therefore, the potential benefit of ticlopidine in this respect is from a clinical point of view certainly only marginal. Minor increases in claudication distances were found with no difference between groups. Smoking habits and lipoproteins were mainly unaltered at the end of the study. It is concluded that platelet inhibition for up to five years has no clear beneficial effect on leg blood flow variables, ankle/brachial index, or walking distances and probably no clinically relevant retarding effect on the slow progression of atherosclerosis. This lack of influence must be distinguished from the antithrombotic effect of ticlopidine, shown as a decreased incidence of acute cardiovascular events and mortality in the authors' multicenter study, STIMS (the Swedish Ticlopidine Multicenter Study).