Peripheral Artery Disease and Intermittent Claudication

Description

Alternative Names

Medications

Managing Leg Pain and Improving Functioning. Agents used for improving leg pain and function are generally those that either prevent blood clots (typically anti-platelet agents) or open blood vessels. Such drugs also reduce the risk for heart disease and stroke. Aspirin is the least intensive anti-platelet agent that is used to reduce cardiovascular risk in patients with PAD. Clopidogrel (Plavix), a more potent platelet inhibitor, is sometimes recommended for patients with PAD and intermittent claudication. Cilostazol is a newer agent that improves blood flow and is proving to useful for disabling intermittent claudication. Other drugs may also be beneficial.

Reducing the Risk for Heart Attack and Stroke. Experts now recommend that PAD patients be given the optimal treatments for managing any heart risk factors as well as treatments for intermittent claudication. All patients should take lifestyle measures to reduce the risk factors that place them in danger of heart attack and stroke. Patients with both diabetes and PAD should be screened for heart disease. Important heart protective drugs for PAD patients include the following:

• The antiplatelet agents used to improve leg function also protect the heart.
• The best protective anti-hypertensive agents for PAD patients may be angiotensin-convertingenzyme (ACE) inhibitors.
• The cholesterol-lowering agents known as statins are proving to have specific benefits for PAD. Other agents may also be helpful.

Aspirin and Other Antiplatelet Agents

So-called antiplatelet drugs increase blood flow by reducing the risk for blood clots. They are used in mild PAD cases, for intermittent claudication, and to prevent blood clots after surgery. These agents are used to improve PAD itself and also to help prevent heart attack and stroke.

Aspirin. Aspirin is the mainstay antiplatelet agent for chronic intermittent claudication, particularly in patients who also are at risk for heart attack and stroke. The drug improves leg circulation and when used early in PAD may prevent clots from forming in the veins. It is taken daily by many PAD patients to reduce the risk for a heart attack or stroke, although it is uncertain if has any effect in delaying or preventing progression of atherosclerosis (hardening of the arteries) itself.

Clopidogrel. Clopidogrel (Plavix) is a powerful oral platelet inhibitor called a thienopyrindine and some experts recommend it for patients with both PAD and intermittent claudication. It may have greater heart and circulatory benefits for patients with PAD than aspirin does. It is showing significant benefits for patients with heart disease. A 2001 report on a major study of patients with acute coronary syndromes found a lower incidence of heart attacks, stroke, and death from heart disease in patients taking clopidogrel compared to those taking aspirin. Ticlopidine (Ticlid) is another effective thienopyrindine and has been used for PAD patients, but dangerous blood disorders, particularly thrombocytopenia, have been reported in patients who had taken it for heart disease.

Phosphodiesterase Inhibitors

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

Cilostazol. Cilostazol (Pletal) has been approved for treating disabling intermittent claudication. A number of studies have now reported improved walking distance and quality of life with its use. It also has other heart-protective properties, including improvements in HDL and triglyceride levels. It is superior to pentoxifylline, the first agent approved for claudication. It is expensive, however, and is currently recommended for patients who do not respond to aspirin or less costly treatments. Common side effects include headache, swelling in the limbs, and gastrointestinal distress that includes diarrhea and flatulence. It does not appear to have adverse effects on the liver or kidney. Similar agents have had serious side effects in patients with heart failure, however, so such individuals should avoid cilostazol.

Dipyridamole. Dipyridamole, another phosphodiesterase inhibitor, may help prevent complications of peripheral artery disease when added to aspirin. Studies are mixed on the benefits of the combination. (The drug does not appear to have any advantages for PAD patients when used alone.)

Thrombolytics (Clot-Busters)

Alteplase (Activase), also called t-PA, and reteplase (Retavase) are thrombolytic agents (commonly known as a "clot-busters"). These agents break up existing clots, and may used in special circumstances. Thrombolytics may be employed in cases of acute vascular occlusion (the sudden development of a blood clot). They may be used as part of a surgical procedure if a clot is present. They are also being investigated as an alternative to surgery in severe cases of PAD. In such events, they can be administered directly into the artery using a specially catheter. They are being researched as the sole agent or with other anti-clotting drugs.

Other Agents Used to Improve Blood Flow in Intermittent Claudication

A number of unique agents are available or under investigation for intermittent claudication. Many are antiplatelet agents that contain other factors that provide additional benefits, including heart protection in some.

Pentoxifylline. Pentoxifylline (Trental) reduces the sticky properties of blood, improving its flow. It is approved in the US for managing claudication, although experts do not recommend its routine use. Unfortunately, major studies have reported only a small effect on walking ability. Some, in fact, reported no additional benefits compared to placebo (a "sugar" pill), although Italian studies published in 2002 found that pentoxifylline was associated with significantly improved walking distance compared to placebo. The most common side effects include headache, nausea (in nearly a third of those taking pentoxifylline), heartburn and gas, dizziness, blurred vision, and flushing.

Prostaglandins. Prostaglandins are vasodilators; they improve blood flow by relaxing smooth muscles and opening the blood vessels. Some may have anti-clotting activity.

• Prostaglandin E1. Early studies on prostaglandin E1 in intermittent claudication were promising. The drug must be injected, however, and more recent studies have not reported significant benefits.
• Beraprost. Early studies using beraprost, a prostaglandin that can be taken orally, suggested that it might extend the limits of exercise in patients with intermittent claudication. Nevertheless, subsequent studies have not confirmed these positive results. The drug may have heart benefits but studies are mixed. Side effects include headache, stomach distress, and anemia, although they appear to be mild. More research is needed.

Naftidrofuryl. Naftidrofuryl (Nafronyl) is available in Europe for intermittent claudication. It is an anti-platelet agent that also blocks serotonin. Such actions enhance the ability for damaged muscle tissue to absorb oxygen from blood. It appears to improve quality of life and treadmill walking, although according to one study, not overall walking distance. It may have benefits for the heart.

FGF-2 and Growth Factors. Growth factors that promote angiogenesis (the production of new blood vessels) are also under investigation. Recombinant fibroblast growth factor-2 (FGF-2) is one such agent. Studies are reporting improved intermittent claudication, even in low doses. It may have severe adverse effects, however, and long-term safety is unknown. A genetically designed agent 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.