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Investigational therapies for treating symptoms of lower extremity peripheral artery disease

Emile R Mohler III, MD
Section Editors
Denis L Clement, MD, PhD
John F Eidt, MD
Joseph L Mills, Sr, MD
Deputy Editor
Kathryn A Collins, MD, PhD, FACS


Pharmacologic therapies used in the treatment of patients with lower extremity peripheral artery disease (PAD) are primarily aimed at improving symptoms or slowing the progression of the disease. Therapies under investigation that may become useful for improving symptoms of claudication to avoid the need for revascularization, promote healing of ischemic ulcers, or alter perception of ischemic pain in patients who are poor candidates or who have failed revascularization attempts are reviewed here. The clinical use of these agents is not yet recommended.

For patients with claudication, convincing evidence of benefit of pharmacologic agents for improving symptoms is available only for cilostazol and naftidrofuryl among the myriad of agents that have been evaluated [1-4]. Recommendations for these and other potentially beneficial pharmacologic agents are discussed separately. (See "Management of claudication", section on 'Beneficial'.)

The best therapeutic option for patients with advanced PAD (eg, rest pain, ischemic ulceration, gangrene) is revascularization (percutaneous or surgical). However, many patients are poor candidates for revascularization due to severe medical comorbidities. (See "Treatment of chronic lower extremity critical limb ischemia".)

Other pharmacologic therapy aimed at reducing the risk for future cardiovascular events in patients with PAD, and which may also limit progression of disease, are reviewed elsewhere. (See "Overview of lower extremity peripheral artery disease" and "Prevention of cardiovascular disease events in those with established disease or at high risk".)


The pathophysiology of the impairments associated with ischemia is complex and provides multiple potential targets for novel drug therapies [5,6]. Potential future pharmacologic therapies that remain to be proven beneficial for the treatment of symptoms associated with lower extremity peripheral artery disease, including claudication, are presented below in alphabetical order. These therapies may be targeted either to improving symptoms of claudication or to more severe manifestations of ischemia, such as ischemic rest pain, ulceration, or gangrene.  


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