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Peripheral artery disease and intermittent claudication - Medications

Description

An in-depth report on the causes, diagnosis, and treatment of peripheral artery disease (PAD).

Alternative Names

Peripheral arterial disease; PAD; Peripheral vascular disease;

Medications:

Treatments for PAD help manage leg pain and improve function, as well as reduce the risk for heart attack and stroke. Drugs used for improving leg pain and function are generally those that either prevent blood clots (typically antiplatelet drugs) or improve blood flow.

Aspirin and Other Antiplatelet Drugs

Antiplatelet drugs reduce the risk for blood clots. Most patients with peripheral artery disease should receive antiplatelet medication. For the most part, this recommendation is made to prevent future death from heart attack or stroke. Antiplatelet drugs may or may not provide benefit for PAD symptoms and progression.

Aspirin is usually the recommended first-line choice. Clopidogrel (Plavix) is recommended as an alternative.

Dipyridamole (Persantine) may help prevent complications of PAD when taken along with aspirin. Studies are mixed on the benefits of the combination. Without aspirin, the drug does not appear to have any advantages for patients with PAD.

Research indicates that adding an anticoagulant drug, such as warfarin (Coumadin), to antiplatelet therapy does not help prevent heart complications of PAD, and can increase the risks for life-threatening bleeding.

[For more information on these drugs, see In-Depth Report #03: Coronary artery disease.]

Phosphodiesterase Inhibitors

Phosphodiesterase inhibitors are drugs that help improve blood flow.

Cilostazol. Cilostazol (Pletal) is used to treat disabling intermittent claudication. A number of studies have reported that the drug helps improve walking distance and quality of life. It also helps improve HDL and triglyceride levels. Cilostazol works better than pentoxifylline, the first drug approved for claudication. It is expensive, however, and currently recommended only for patients with moderate-to-severe intermittent claudication who do not respond to aspirin or less costly treatments. Common side effects include headache, swelling in the limbs, and stomach problems such as diarrhea and flatulence (gas). It does not appear to have bad effects on the liver or kidney. Similar drugs have had serious side effects in patients with heart failure, so these patients should avoid cilostazol.

Pentoxifylline. Pentoxifylline (Trental) reduces the sticky properties of blood, improving its flow. It is approved in the U.S. for managing claudication, although doctors do not recommend its routine use. Studies regarding the drug's effectiveness have been mixed. Some studies have reported a small effect on walking ability; another found the drug significantly improved walking distance. Other research has found that the drug does not work any better than a dummy pill (placebo). The most common side effects include headache, nausea, heartburn, flatulence (gas), dizziness, blurred vision, and flushing.

Thrombolytics (Clot-Busters)

Alteplase (Activase), also called t-PA, and reteplase (Retavase) are thrombolytic drugs. Such drugs are commonly called "clot-busters." They break up existing clots, and may be used in cases of acute vascular occlusion (the sudden development of a blood clot). They may also be used if a clot is present. Researchers are investigating whether thrombolytics are an effective alternative to surgery in severe cases of PAD. In severe cases, the drugs can be delivered directly into the artery.

Other Drugs Used to Treat Intermittent Claudication

ACE Inhibitors. ACE inhibitors are a type of drug used to treat high blood pressure. The ACE inhibitor ramipril (Altace) is often recommended for patients with symptomatic peripheral artery disease, primarily to reduce the risk of cardiovascular events.

Resources

References

Aboyans V, Criqui MH, Denenberg JO, Knoke JD, Ridker PM, Fronek A. Risk factors for progression of peripheral arterial disease in large and small vessels. Circulation. 2006 Jun 6;113(22):2623-9.

Arain FA, Cooper LT Jr. Peripheral arterial disease: diagnosis and management. Mayo Clin Proc. 2008 Aug;83(8):944-49; quiz 949-50.

Aung PP, Maxwell HG, Jepson RG, Price JF, Leng GC. Lipid-lowering for peripheral arterial disease of the lower limb. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000123.

Collins R, Burch J, Cranny G, Aguiar-Ibáñez R, Craig D, Wright K, et al. Duplex ultrasonography, magnetic resonance angiography, and computed tomography angiography for diagnosis and assessment of symptomatic, lower limb peripheral arterial disease: systematic review. BMJ. 2007 Jun 16;334(7606):1257. Epub 2007 Jun 4

Creager MA and Libby P. Peripheral arterial disease. In: Libby P, Bonow RO, Mann DL, Zipes DP, eds. Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 8th ed. Saunders; 2007:chap 57.

Garg PK, Tian L, Criqui MH, Liu K, Ferrucci L, Guralnik JM, et al. Physical activity during daily life and mortality in patients with peripheral arterial disease. Circulation. 2006 Jul 18;114(3):242-8.

Kikano GE, Brown MT. Antiplatelet therapy for atherothrombotic disease: an update for the primary care physician. Mayo Clin Proc. 2007 May;82(5):583-93.

McDermott MM, Ades P, Guralnik JM, Dyer A, Ferrucci L, Liu K, et al. Treadmill exercise and resistance training in patients with peripheral arterial disease with and without intermittent claudication: a randomized controlled trial. JAMA. 2009 Jan 14;301(2):165-74.

Met R, Bipat S, Legemate DA, Reekers JA, Koelemay MJ. Diagnostic performance of computed tomography angiography in peripheral arterial disease: a systematic review and meta-analysis. JAMA. 2009 Jan 28;301(4):415-24.

Saw J, Bhatt DL, Moliterno DJ, Brener SJ, Steinhubl SR, Lincoff AM, et al. The influence of peripheral arterial disease on outcomes: a pooled analysis of mortality in eight large randomized percutaneous coronary intervention trials. J Am Coll Cardiol. 2006 Oct 17;48(8):1567-72.

Sobel M, Verhaeghe R; American College of Chest Physicians; American College ofChest Physicians. Antithrombotic therapy for peripheral artery occlusive disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):815S-843S.

Steg PG, Bhatt DL, Wilson PWF, D’Agostino R, Ohman EM, Rother, J. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA. Mar 21 2007;29(11)7:1197-1206.

Warfarin Antiplatelet Vascular Evaluation Trial Investigators, Anand S, Yusuf S, Xie C, Pogue J, Eikelboom J, et al. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med. 2007 Jul 19;357(3):217-27.

  • Reviewed last on: 5/13/2009
  • Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
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