Randomized trial of the effects of low-dose calcium-heparin in patients with peripheral arterial disease and claudication

PURPOSE: We performed a long-term, multicenter, randomized, double-blind trial to evaluate the efficacy and tolerability of low-dose, subcutaneous calcium-heparin (12,500 IU/day) in comparison with placebo in patients with stable peripheral arterial disease of the lower extremities. PATIENTS AND METHODS: At the end of a 2-week wash-out period, during which aspirin placebo was given, 201 patients were randomly assigned to receive either subcutaneous calcium-heparin or placebo for two 3-month treatment periods, each of which was followed by a 6-month period of observation. All of the patients were given low-dose aspirin (50 mg/day) throughout the 18-month study. The main efficacy variables were pain-free and maximum walking time (by standard treadmill test). Patients answered a questionnaire about pain and the limitation of daily activities. Results were analyzed by intention-to-treat. RESULTS: At the end of the study, the estimated increase in pain-free walking time was 39% in the heparin group and 23% in the placebo group (P = 0.09). The estimated increase in maximum walking time was 40% in the heparin group and 16% in the placebo group (P = 0.05). Patients treated with heparin also reported that they had to stop walking because of leg pain, or had daily activities limited by leg pain, less frequently than the placebo group (P