Combination therapy with warfarin plus clopidogrel improves outcomes in femoropopliteal bypass surgery patients

Background: Patients having undergone femoropopliteal bypass surgery remain at significant risk of graft failure. Although antithrombotic therapy is of paramount importance in these patients, the effect of oral anticoagulation therapy (OAT) on outcomes remains unresolved. We performed a randomized, prospective study to assess the impact of OAT plus clopidogrel vs dual antiplatelet therapy on peripheral vascular and systemic cardiovascular outcomes in patients who had undergone femoropopliteal bypass surgery. Methods: Three hundred forty-one patients who had undergone femoropopliteal surgery were enrolled and randomized: 173 patients received clopidogrel 75 mg/d plus OAT with warfarin (C + OAT), and 168 patients received dual antiplatelet therapy with clopidogrel 75 mg/d plus aspirin 100 mg/d (C + acetylsalicylic acid [ASA]). Study end points were graft patency and the occurrence of severe peripheral arterial ischemia, and the incidence of bleeding episodes. Results: Follow-up ranged from 4 to 9 years. The graft patency rate and the freedom from severe peripheral arterial ischemia was significantly higher in C + OAT group than in C + ASA group (P = .026 and .044, respectively, Cox-Mantel test). The linearized incidence of minor bleeding complications was significantly higher in C + OAT group than in C + ASA group (2.85% patient-years vs 1.37% patient-years; P = .03). The incidence of major adverse cardiovascular events, including mortality, was found to be similar (P = .34) for both study groups. Conclusions: In patients who have undergone femoropopliteal vascular surgery, combination therapy with clopidogrel plus warfarin is more effective than dual antiplatelet therapy in increasing graft patency and in reducing severe peripheral ischemia. These improvements are obtained at the expenses of an increase in the rate of minor anticoagulation-related complications. (J Vasc Surg 2012;56:96-105.)