Atherothrombosis, characterized by
atherosclerotic plaque rupture and subsequent occlusive or subocclusive
thrombus formation is the primary cause of acute ischemic syndromes involving all vascular beds and accounts for more than one-third of all deaths in the developed world. Platelet activation and aggregation constitute the most critical component in the pathophysiology of atherothrombotic disease.
Aspirin is currently the most commonly used
antiplatelet agent and one of the most frequently prescribed drugs, with as many as 30 million Americans on chronic
aspirin regimens. Multiple well-designed prospective randomized clinical trials have demonstrated
aspirin's efficacy in both primary and
secondary prevention of a wide variety of entities that the atherothrombotic disease spectrum encompasses, such as cerebrovascular, coronary artery, and
peripheral vascular disease. Despite its proven benefit, however, a growing body of evidence suggests that up to 70% of
aspirin-takers may still be at risk for atherothrombotic complications due to resistance. Patients with laboratory-confirmed
aspirin resistance seem to have an almost fourfold increase in their risk for acute thrombotic episodes, which underlines the magnitude of the problem for the vascular specialist. In this article, we review the physiology of platelet activation and the role of
aspirin as an
antiplatelet agent; the various laboratory assays used in assessing
aspirin effectiveness; and current data on
aspirin resistance and its clinical implications in patients with
cardiovascular disease. We also review the studies that explore this phenomenon in patients with
peripheral arterial disease and discuss the optimal management options in
aspirin-resistant individuals. Suggestions are advanced for the direction of future trials evaluating
aspirin resistance in patients with
vascular disease.