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Peripheral artery disease and intermittent claudication

Description

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

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 anti-platelet drugs) or open blood vessels. Such drugs also help protect the heart.

Experts 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 thin the blood and reduce the risk for clots. They are used in mild PAD cases, for intermittent claudication, and to prevent blood clots after surgery.

Aspirin. Aspirin is the main antiplatelet drug use to treat chronic intermittent claudication, particularly in patients who also are at risk for heart attack and stroke. The drug improves leg circulation and, when used in early PAD, may prevent clots from forming in the veins.

Clopidogrel. Clopidogrel (Plavix) is a powerful type of drug called a thienopyridine. Some experts recommend it for patients with both PAD and intermittent claudication. In patients with PAD, it may protect the heart and arteries better than aspirin. Ticlopidine (Ticlid) is another effective thienopyridine that has been used for patients with PAD, but dangerous blood disorders, (particularly thrombocytopenia), have been reported in patients who had taken it for heart disease.

Phosphodiesterase Inhibitors

Phosphodiesterase inhibitors are drugs that help keep blood vessels open and blood flowing.

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 only recommended 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 such individuals 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.

Dipyridamole. Dipyridamole 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.

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 during 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

Ramipril . The ACE inhibitor ramipril (Altace) improved blood flow to the legs, reduced leg pain, and helped maximize walking time in a small 2006 study of patients with intermittent claudication. Researchers still have to study whether this medication works best for specific patients (such as those with high blood pressure or diabetes).

Naftidrofuryl. Naftidrofuryl (Nafronyl) is available in Europe for intermittent claudication. It is not approved in the United States. Nafronyl is an anti-platelet drug that also blocks serotonin. This action helps damaged muscle tissue absorb more oxygen from blood. Nafronyl appears to improve quality of life and treadmill walking. However, one study found it did not improve overall walking distance.

Investigational Drugs and Treatments

Growth Factors. Growth factors help new blood vessels grow, an action called angiogenesis. Studies show that recombinant fibroblast growth factor-2 (FGF-2) improves intermittent claudication, even in low doses. The drug may have severe side effects, and long-term safety is unknown. A drug called vascular endothelial growth factor (VEGF) is also under investigation.

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.

Phlebotomy . Phlebotomy, the removal of blood from the body, is sometimes used to reduce the excess iron that accumulates in patients with PAD. However, a 2007 Journal of the American Medical Association study found that reducing iron stores did not significantly lower the risk of heart attack, stroke, or death in patients with PAD.

• Review Date: 3/29/2007
• Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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