Atherosclerotic peripheral arterial disease is associated with an increased risk of myo- cardial infarction, stroke, and death from cardiovascular causes. Antiplatelet drugs reduce this risk, but the role of oral anticoagulant agents in the prevention of car- diovascular complications in patients with peripheral arterial disease is unclear.

Methods

We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent (target international normal- ized ratio [INR], 2.0 to 3.0) or to antiplatelet therapy alone. The first coprimary out- come was myocardial infarction, stroke, or death from cardiovascular causes; the sec- ond coprimary outcome was myocardial infarction, stroke, severe ischemia of the peripheral or coronary arteries leading to urgent intervention, or death from cardio- vascular causes.

Results

A total of 2161 patients were randomly assigned to therapy. The mean follow-up time was 35 months. Myocardial infarction, stroke, or death from cardiovascular causes oc- curred in 132 of 1080 patients receiving combination therapy (12.2%) and in 144 of 1081 patients receiving antiplatelet therapy alone (13.3%) (relative risk, 0.92; 95% con- fidence interval [CI], 0.73 to 1.16; P=0.48). Myocardial infarction, stroke, severe ische- mia, or death from cardiovascular causes occurred in 172 patients receiving combina- tion therapy (15.9%) as compared with 188 patients receiving antiplatelet therapy alone (17.4%) (relative risk, 0.91; 95% CI, 0.74 to 1.12; P=0.37). Life-threatening bleed- ing occurred in 43 patients receiving combination therapy (4.0%) as compared with 13 patients receiving antiplatelet therapy alone (1.2%) (relative risk, 3.41; 95% CI, 1.84 to 6.35; P<0.001).

Conclusions

In patients with peripheral arterial disease, the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in pre- venting major cardiovascular complications and was associated with an increase in life-threatening bleeding.