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

Abstract

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 <0.01). CONCLUSIONS: Treatment with low-dose subcutaneous calcium-heparin is safe and effective in improving walking performance and reducing physical disability in patients with stable peripheral arterial disease and claudication.