Effect of picotamide on the clinical progression of peripheral vascular disease. A double-blind placebo-controlled study. The ADEP Group.

BACKGROUND: Patients with peripheral vascular disease (PVD) undergo a clinical course that can be complicated by cardiovascular events occurring in several areas of the circulation. METHODS AND RESULTS: In the present study we investigated the ability of picotamide, a substance that inhibits platelet thromboxane A2 (TxA2) synthase and antagonizes TxA2 receptors, to reduce cardiovascular complications in PVD patients. The study was double blind and placebo controlled. After a 1-month run-in period, 2,304 patients were randomly allocated to either placebo or picotamide (300 mg t.i.d.) and followed for 18 months. Major and minor events were analyzed. Results of an "intention-to-treat analysis" were that patients on picotamide suffered 45 major events (3.9%) and 77 minor events (6.7%), whereas those taking placebo suffered 52 major (4.5%) and 99 minor events (8.6%). There was borderline statistical difference between the two groups with respect to the sum of the major and minor events (risk reduction, 18.9%; p = 0.056, log-rank test). Results of an "on-treatment" analysis were that patients on picotamide suffered 40 major (3.8%) and 66 minor events (6.3%), whereas those taking placebo suffered 45 major (4.2%) and 95 minor events (8.9%). The sum of both major and minor events was 106 (10.1%) in the picotamide group and 140 (13.1%) in the placebo group. This difference was significant (risk reduction, 23%; p = 0.029, log-rank test). CONCLUSIONS: The results of this study indicate that picotamide reduces cardiovascular complications in PVD patients. The apparently low effect of this drug in reducing major events suggests that further studies be made with picotamide in PVD patients who are at high risk of cardiovascular complications so as to further assess its clinical efficacy.