Peripheral arterial disease: Pathophysiology, risk factors, and role of antithrombotic therapy

Objective: To provide an overview of the impact of peripheral arterial disease (PAD) and the steps that can be taken to reduce its burden through greater awareness of the disease, improved diagnosis, and better treatment, with emphasis on the use of antiplatelet agents. Data Sources: Recent (1990-2003) published scientific literature, as identified by the author through Medline searches, using the terms peripheral arterial disease, atherothrombosis, pathophysiology, risk factors, treatment, clinical trials, and reviews on treatment. Study selection: Recent systematic English-language review articles and reports of controlled randomized clinical trials were screened for inclusion. Data Synthesis: PAD is a distinct atherothrombotic syndrome marked by stenosis and occlusion of peripheral arterial beds, typically those in the lower extremities. Symptoms range from intermittent claudication (IC) during exercise to peripheral limb ischemia requiring limb amputation. IC, the most common symptom, is experienced by 2% to 3% of men and 1% to 2% of women aged 60 years and older. Despite its recognition as a major atherothrombotic risk factor, PAD is not widely appreciated by clinicians, and most cases remain undiagnosed. Asymptomatic PAD, as indicated by a reduced ankle brachial systolic pressure index, should alert the health care provider to the presence of diffuse atherothrombotic disease and need for treatment. Risk factors for development and progression of PAD include smoking, hypertension, diabetes, hyperlipidemia, and physical inactivity. The aim of pharmacotherapy is to improve the symptoms of PAD (especially IC), defer onset of limb-threatening ischemia, and improve long-term survival. Successful treatment strategies include risk factor modification, particularly smoking cessation; initiation of regular exercise; control of hypertension, diabetes, and hyperlipidemia; and use of antiplatelet agents to reduce the risk of atherothrombotic events. Available data suggest that aspirin reduces morbidity and mortality in PAD, while clopidogrel reduces the risk of atherothrombotic events such as myocardial infarction and stroke in these patients. Conclusion: Increased awareness among members of the health care community about the prevalence of PAD and benefits associated with risk-factor reduction and antiplatelet therapy could produce substantial decreases in the burden of this disease.