An RCT 1 with 2 161 subjects with peripheral arterial disease compared combination therapy with an antiplatelet agent (aspirin, ticlopidine, or clopidogrel) and an oral anticoagulant agent (warfarin or acenocoumarol, target INR 2.0 to 3.0) with antiplatelet therapy alone. The mean follow-up time was 35 months. Myocardial infarction, stroke, or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy (12.2%) and in 144 of 1081 patients receiving antiplatelet therapy alone (13.3%) (RR 0.92, 95% CI 0.73 to 1.16, P=0.48). Myocardial infarction, stroke, severe ischemia, or death from cardiovascular causes occurred in 172 patients receiving combination therapy (15.9%) as compared with 188 patients receiving antiplatelet therapy alone (17.4%) (RR 0.91, 95% CI 0.74 to 1.12, P=0.37). Life-threatening bleeding occurred in 43 patients receiving combination therapy (4.0%) as compared with 13 patients receiving antiplatelet therapy alone (1.2%) (RR 3.41, 95% CI 1.84 to 6.35, P<0.001).
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