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WAVE a Red Flag for Combination Antithrombotic Therapy

Adding an anticoagulant to antiplatelet therapy did not reduce risk for cardiovascular events in patients with PAD.

Patients with peripheral arterial disease have an increased risk for cardiovascular events. In response to great interest in strategies that might reduce that risk, investigators from seven countries tested whether the combination of antiplatelet and anticoagulant therapy is superior to antiplatelet therapy alone at reducing the risk for cardiovascular death, MI, stroke, or severe ischemia of the coronary or peripheral arteries necessitating intervention. The Warfarin Antiplatelet Vascular Evaluation (WAVE) trial investigators randomized 2161 patients (mean age, 64; 73.6% men) who had peripheral arterial disease but were not at high risk for bleeding and had no recent stroke, dialysis treatment, or other indication for oral anticoagulation. After a 2- to 4-week run-in period on combination therapy, patients were given aspirin, ticlopidine, or clopidogrel alone or in combination with warfarin or acenocoumarol.

Mean follow-up duration was 35 months. International normalized ratios were within the target range of 2.0 to 3.0 at 62% of follow-up visits. Incidence of the composite endpoint of cardiovascular death, MI, and stroke was similar between the combination-therapy group (12.2%) and the antiplatelet-only group (13.3%; relative risk, 0.92; P=0.48). Incidence of another composite endpoint of the same events plus severe ischemia of the coronary or peripheral arteries necessitating intervention was also similar between the two groups (15.9% vs. 17.4%; RR, 0.91; P=0.37). The combination-therapy group had an increased risk for life-threatening bleeding (4.0% vs. 1.2%; RR, 3.41; P<0.001).

Comment: This trial does not support combining anticoagulants with antiplatelet therapy to reduce the risk for cardiovascular events in patients with peripheral arterial disease.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology July 18, 2007

Citation(s):

The Warfarin Antiplatelet Vascular Evaluation Trial Investigators. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med 2007 Jul 19; 357:217-27.

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