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.

Doctors now recommend that patients with PAD be given treatments for managing both heart risk factors and intermittent claudication.

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 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 experts 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.

Investigational Drugs and Treatments

Growth Factors. Growth factors help new blood vessels grow, an action called angiogenesis. The results of high-quality clinical trials have been disappointing. Growth factors may have severe side effects, and long-term safety is unknown.

Mesoglycan. Mesoglycan has been studied for a few years. This drug breaks up blood clots, and studies have suggested that oral mesoglycan may improve walking distance.

Prostaglandins. Prostaglandins relax smooth muscles and open the blood vessels, which improves blood flow. These types of drugs are called vasodilators. Some may have anti-clotting activity.

• Prostaglandin E1. Early studies on prostaglandin E1 in intermittent claudication have been promising. However, more recent studies have not reported significant benefits. The drug is injected.
• Beraprost. Beraprost is a prostaglandin that can be taken by mouth. Early studies suggested that it might allow patients with intermittent claudication to exercise for longer periods of time. Subsequent studies have not confirmed these positive results. Side effects include headache, stomach distress, and anemia, although they appear to be mild.