Peripheral arterial disease is a prevalent manifestation of atherosclerosis that is associated with significant risk of morbidity and mortality and also a marked reduction in ambulatory capacity and quality of life. Unfortunately, PAD is undertreated with regard to risk factor modification, use of antiplatelet therapies, and management of symptoms. The data to support intensive risk modification in PAD patients have not been as extensively established as is the case for patients with coronary artery disease.

Clinical trials specifically in the PAD population are needed to address the benefits of the treatment of hyperlipidemia (including not only LDL cholesterol reduction, but also modification of other lipid fractions), diabetes, elevated homocysteine levels, and other prevalent risk factors in PAD. Despite these limitations, patients with PAD should be considered candidates for secondary disease prevention strategies.

Target goals for the management of atherosclerotic risk factors should be achieved in all PAD patients. The use of ACE inhibitors may confer additional benefits in terms of a reduction in the risk of fatal and nonfatal ischemic events. The data are better in support of the use of antiplatelet therapies to prevent ischemic events in PAD. Aspirin should be considered in all PAD patients, with clopidogrel an alternate (and potentially more effective) agent. Studies evaluating the combination of clopidogrel with aspirin or aspirin with other antiplatelet agents are needed.

Medical therapies to treat the symptoms of claudication and limited mobility are now well established. A supervised walking exercise program should first be considered in all patients, given the low risk and marked improvements seen in functional capacity. Pharmacologic therapies are also available that offer meaningful improvements in functional status. Pentoxifylline has limited utility, but cilostazol has been shown to improve both treadmill walking capacity and quality of life.

Peripheral Arterial Disease Introduction Epidemiology Risk Factors Pathogenesis Clinical Presentation and Diagnosis Medical Therapy Antiplatelet Therapy Claudication Medical Therapy Interventional Therapy for PAD Critical Leg Ischemia in Peripheral Arterial Disease Conclusions References

A number of other compounds such as propionyl-l-carnitine, pros-taglandins, L-arginine, lipid-lowering drugs, and angiogenic growth factors are under investigation for both claudication and critical leg ischemia. Future studies may confirm the benefits of combining treatments for claudication, including exercise following angioplasty or exercise plus a medication.

Patients who do not respond to medical therapies for their claudication symptoms should be considered for angioplasty if they have a lesion amenable to the procedure. Patients with critical leg ischemia should be initially considered for vascular surgery and/or angioplasty.