In addition to risk factor modification, other therapies have been targeted to slow the progression of peripheral atherosclerosis, as well as to decrease the risk of cardiovascular morbidity and mortality. The role of platelets in thrombus formation has led to many studies in the effectiveness of various antiplatelet agents, particularly aspirin, in the prevention of ischemic events. The meta-analysis by the Antiplatelet Trialists’ Collaboration concluded that, in patients with a history of myocardial infarction or stroke, antiplatelet therapy reduced the risk of ischemic events by approximately 25%.

In patients with PAD treated with bypass surgery, the Antiplatelet Trialists’ Collaboration also found that antiplatelet therapy significantly promoted graft patency following vascular surgery. Thus, it would seem prudent to treat patients with PAD with low-dose aspirin.

In patients with PAD, ticlopidine has been shown to be more effective than placebo at reducing the risk of fatal and nonfatal myocardial infarction and stroke. This observation has led to the development of other drugs including clopidogrel, which lacks many of the side effects of ticlopidine. The clopidogrel versus aspirin for the prevention of ischemic events (CAPRIE) trial demonstrated that PAD patients showed a 24% risk reduction on clopidogrel as compared to aspirin in terms of reducing risk for ischemic events.

In summary, patients with PAD frequently have a history of coronary artery disease and stroke, and even in the absence of this history, PAD remains an independent predictor of cardiovascular morbidity and mortality. Aspirin should be considered as the primary antiplatelet agent for preventing ischemic events in PAD. Aspirin is also effective in maintaining vascular graft patency and may prevent thrombotic complications of PAD. Clopidogrel has FDA approval for the prevention of ischemic events in PAD, and, although based on a subgroup analysis, clopidogrel may be more effective than aspirin in PAD patients.

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