Review
Current medical therapies for patients with peripheral arterial disease: a critical review

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Abstract

There is a paucity of trials that specifically evaluate the benefits of cardiovascular risk reduction therapies in patients with peripheral arterial disease. We therefore sought to describe the data supporting the use of therapies for lowering cardiovascular risk, preventing ischemic events, as well as managing intermittent claudication, in these patients. A search for randomized, placebo-controlled trials in peripheral arterial disease was conducted using Medline and reference lists of relevant articles. These trials served as the primary sources of data and treatment recommendations, while observational studies and case series were included as sources of commonly accepted treatment recommendations that were not fully supported by the randomized trial. Data from the primary sources support the use of antiplatelet therapy and, potentially, of angiotensin-converting enzyme inhibitors, for preventing ischemic events. In contrast, the evidence demonstrates a nonsignificant trend for treating dyslipidemia to prevent mortality and does not specifically support intensive glycemic control in persons with diabetes or estrogen use in these patients. However, observational data and data derived from trials in persons with other manifestations of cardiovascular disease may be generalized to support the importance of treating key risk factors, such as smoking, diabetes, dyslipidemia, and hypertension. Data supporting the use of estrogen to reduce cardiovascular risk are less clear. Studies do demonstrate improvement in walking ability resulting from exercise rehabilitation programs, as well as from use of cilostazol and, to a more modest degree, pentoxifylline. The consensus is to treat risk factors of peripheral arterial disease patients similarly to patients with other manifestations of atherosclerosis and to use exercise rehabilitation or cilostazol to treat the subset of patients with claudication.

Section snippets

Selection criteria

We searched Medline and the reference lists of relevant articles for treatment trials that included patients with peripheral arterial disease. Disease-related terms included peripheral arterial disease, peripheral vascular disease, peripheral atherosclerosis, claudication, and intermittent claudication. Risk factor–related or drug-related terms included lipids, dyslipidemia, hyperlipidemia, hypertension, diabetes, smoking, estrogen, menopause, antiplatelet, angiotensin-converting enzyme (ACE),

Antiplatelet therapy

The Antiplatelet Trialists’ Collaboration evaluated the efficacy of prolonged (1 month or longer) antiplatelet therapy (in most cases, aspirin) in preventing vascular events, including nonfatal myocardial infarction, stroke, and vascular death (19). This meta-analysis combined data from 145 randomized studies involving more than 100,000 patients, including approximately 70,000 high-risk patients with evidence of cardiovascular disease, such as myocardial infarction, stroke, or transient

Treatment of cardiovascular risk factors

The most common cardiovascular risk factors for peripheral arterial disease include smoking, diabetes, hypertension, dyslipidemia, and abnormalities of homocysteine metabolism, as well as lower estrogen levels after menopause. There is insufficient level 1 or 2 evidence to support the relation between treatment of these risk factors and improved cardiovascular outcomes in persons with peripheral arterial disease. Nonetheless, expert consensus publications strongly recommend treating these risk

Medical treatment of claudication

Medical therapy for claudication includes exercise rehabilitation as well as two drugs approved by the FDA. There are other therapeutic agents in development for this indication, but they await further development.

Treating peripheral arterial disease: evidence versus consensus

Evidence available for cardiovascular risk reduction therapies in patients with peripheral arterial disease supports the use of antiplatelet drugs, in particular clopidogrel. Similarly, data also suggest that ACE inhibitor therapy is likely to be effective. However, these conclusions were derived from subgroup analyses of trials in patients with a broad range of atherosclerotic disease manifestations. Consensus opinion based on evidence from trials in patients with other manifestations of

Acknowledgements

Our thanks to Dr. Gillian Leng for her helpful responses to queries regarding this manuscript.

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