Peripheral arterial disease (PAD) is a highly prevalent but largely undiagnosed condition that affects an estimated 27 million people in Europe and North America. Caused by atherosclerotic occlusion of the leg arteries, PAD is associated with an increased risk of cardiovascular and cerebrovascular events, including death, myocardial infarction (MI), and stroke. It’s also associated with a higher total mortality compared with other manifestations of atherosclerosis. Despite an expanding treatment armamentarium for the condition, PAD patients continue to be undiagnosed and face a high incidence of cardiovascular events.

A definitive diagnosis of PAD may not always be evident, even in symptomatic patients. For example, similar symptoms may be caused by arthritis of the hip or knee joint or by sciatica. A typical symptom is claudication in the legs—exertional pain while walking, particularly walking longer distances and up inclined surfaces. However, some patients may experience atypical claudication. Instead of describing their symptoms as exertional pain, patients may report that their legs are easily fatigued or cramp during the day with activity. This can easily be mistaken for old age; therefore, greater physician awareness of PAD overall and improved knowledge of atypical claudication may enhance the detection of PAD.

Patients with asymptomatic PAD are still at increased risk of cardiovascular events, particularly MI and stroke. Other than the systemic risk associated with PAD, limb-threatening ischemia and amputation may also occur. However, the risk of developing limb-threatening ischemia is relatively low in patients with asymptomatic PAD.


In an effort to improve the medical treatment of PAD, the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial was conducted. It enrolled patients with documented coronary artery disease, cardiovascular disease, symptomatic PAD, or multiple atherothrombotic risk factors and investigated the use of clopidogrel plus low-dose aspirin compared with low-dose aspirin alone in patients with these conditions. Currently, guidelines from the American College of Cardiology and the American Heart Association recommend either clopidogrel or aspirin alone for patients with symptomatic PAD.

In a post hoc subgroup analysis, my colleagues and I evaluated patients from the CHARISMA trial who were identified as having PAD, most of whom were symptomatic. Results demonstrated that dual therapy of clopidogrel plus aspirin reduced the rate of MI in patients with PAD compared with patients taking aspirin alone as well as reduced the rate of hospitalization for ischemic events. There were, however, increased rates of minor bleeding when clopidogrel was added to aspirin treatment. The data from CHARISMA showed that dual antiplatelet therapy in stable PAD patients appears to provide some protection against MI. Future trials will need to validate the results prospectively, but the early indications are that this may be a promising treatment approach for select patients.

On the Alert for PAD

Physicians should be vigilant for PAD, even in the absence of the classic symptoms of claudication. If a PAD diagnosis is in question, screening for the condition is safe and inexpensive. For example, an ankle brachial index, pulse volume recording (PVR) alone, or PVR while exercising can be used. There are many options available to improve patients’ symptoms and future ischemic risk, including lifestyle modification, medical therapy, and surgical procedures. Smoking cessation, institution of a walking program, and statin therapy are particularly important. It is essential that physicians become aware of and familiar with the symptomatic and asymptomatic characteristics of this disease.