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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;

Reducing Heart Risks

If a patient cannot control heart risk factors with lifestyle measures, treatment may be needed.

Drug Treatment for Unhealthy Cholesterol and Lipid Levels

It is very important for people with PAD to keep their LDL ("bad cholesterol") levels to below 100 mg/dL. If patients have serious heart disease risk factors (high blood pressure, diabetes, other unhealthy lipids) in addition to PAD, they may need to aim for LDL levels below 70 mg/dL. Aggressive control of cholesterol levels is known to reduce death rates in patients with peripheral artery disease (PAD). Unhealthy cholesterol levels are major contributors to atherosclerosis, the common factor in PAD and heart disease. Many experts now recommend that patients with PAD receive drugs to lower cholesterol.

There are a number of drugs available for lowering cholesterol. Those discussed in this report are believe to have particular benefits for patients with PAD. [For more information on these cholesterol-lowering drugs, see In-Depth Report #23: Cholesterol.]

Statins. Statins are the most effective drugs for the treatment of high cholesterol. Statins block the liver enzyme hMG-CoA reductase, which the body uses to make cholesterol. Statins are particularly effective for lowering LDL levels and triglycerides. They also raise HDL levels, but not as much as other anti-cholesterol drugs.

Statins include:

• Lovastatin (Mevacor)
• Pravastatin (Pravachol)
• Simvastatin (Zocor)
• Fluvastatin (Lescol)
• Atorvastatin (Lipitor)
• Rosuvastatin (Crestor)

Statins reduce the risk of heart attack and stroke. Evidence strongly suggests that statins have specific benefits for patients with PAD. In a 2003 study, statin use was associated with improved leg function, regardless of the patients' cholesterol levels.

• Statins improve the function of the lining of blood vessels, which improves blood flow.
• Statins appear to reduce inflammation in the arteries, which is now believed to be a major factor in blood vessel injury.
• Some evidence suggests that statins might promote growth of new blood vessels and help prevent intermittent claudication.

Side effects of statins include headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

Statins can also cause an uncommon condition called myopathy. Myopathy cause muscle damage and, in some cases, muscle and joint pain. The risk for myopathy increases with higher doses. The following increases one's risk of myopathy

• Older age
• Small size or frailty
• Alcohol abuse
• Hypothyroidism
• Use of multiple medications

There is also a higher risk of myopathy if statins are used before surgery.

Statins also can effect the liver, particularly at higher doses, so periodic liver function tests should be done. Statins should not be taken by anyone with liver problems or by women who are pregnant or breast-feeding.

Nicotinic Acid (Niacin). Nicotinic acid is the active compound found in niacin (vitamin B3). It raises HDL levels more than any other anti-cholesterol drug, and is the first choice for patients with low HDL levels. Nicotinic acid is also extremely effective in reducing triglyceride levels. It may be beneficial for some patients with PAD.

Brands of nicotinic acid include Niacor, Nicolar, and Slo-Niacin. An extended-release form (Niaspan), taken at bedtime, may have fewer side effects than other types of niacin. Although niacin is available over-the-counter, the active form used for cholesterol is given in much higher doses and is available only by prescription. It is important to take this medication under a doctor's direction in order to ensure its safety and effectiveness. Combinations with other drugs, particularly statins, may add significant benefits.

Many patients can not tolerate the side effects of niacin. About a quarter of patients taking rapid-acting forms of nicotinic acid stop taking them. The most common side effects are flushing of the face and neck, itching, headache, blurred vision, and dizziness. They can occur between 5 minutes to hours after taking the drug and can last for varying lengths of time. The body does get used to these effects eventually, so they generally go away. Gastrointestinal problems are common. Other side effects include dry skin and mucous membranes and darkening of the skin.

About 3 - 5% of people taking nicotinic acid develop liver abnormalities, which go away after the medication is stopped. The extended form of Niaspan appears to be safe for the liver, but people with chronic liver disease should not use any form of nicotinic acid. People with gout should avoid nicotinic acid, since it elevates uric acid.

The role of nicotinic acid in people with diabetes is less clear. About 30% of patients who take niacin have a jump in blood glucose levels. But some studies have reported that diabetics who use niacin had little trouble with glucose control. Niacin's effects on HDL and triglycerides are especially suited for the lipid imbalances that are common in diabetes.

Fibrates. Fibrates (sometimes called fibric acid derivatives) break down the particles that make triglycerides. Gemfibrozil (Lopid) is the standard fibrate. Newer fibrates, including fenofibrate (Tricor) and bezafibrate (Bezalip), may be more effective in lowering cholesterol than gemfibrozil. Most fibrates have been shown to lower the risk of heart attack. A study on fenofibrate suggested that it reduced certain clotting factors (another risk factor for heart disease).

Fibrates may be good choices for many patients who need to lower triglyceride levels and increase HDL, but who cannot take nicotinic acid.

In one study, patients with PAD who took bezafibrate experienced fewer non-fatal heart attacks and the severity of intermittent claudication was reduced.

Side effects of fibrates may include gastrointestinal discomfort, aching muscles, sensitivity to sunlight, and skin rashes. Impotence has been associated with fibrates in less than 1% of patients. Fibrates have been known to cause gallstones, so people with gallbladder problems should not use these drugs. The drugs may cause abnormal heart rhythms and can affect the liver and kidney. They interact with a number of drugs including warfarin, some oral drugs used for diabetes, and certain antibiotics. Fibrates also interact with grapefruit juice.

Managing High Blood Pressure

Evidence suggests that best drugs for patients with high blood pressure and PAD may be angiotensin-converting-enzyme (ACE) inhibitors. These drugs block the effects of the angiotensin-renin-aldosterone system, which is thought to have many harmful effects on the heart and blood vessels.

ACE inhibitors include:

• Captopril (Capoten)
• Enalapril (Vasotec)
• Quinapril (Accupril)
• Benazepril (Lotensin)
• Ramipril (Altace)
• Perindopril (Aceon)
• Lisinopril (Prinivil, Zestril)

They are important drugs for patients with PAD and diabetes who also have high blood pressure.

Side effects include an irritating cough, excessive drop in blood pressure, and allergic reactions. In some people, the cough is intolerable. Iron supplements or the drug picotamide may help reduce the frequency of coughs.

One rare, but severe, side effect is granulocytopenia, which is an extreme reduction in white blood cells.

In rare cases (0.3%), patients who take ACE inhibitors suffer a sudden and severe allergic reaction called angioedema, which causes swelling in the eyes and mouth and may close off the throat.

Although ACE inhibitors can protect against kidney disease, they also increase potassium retention in the kidneys. This increases the risk for cardiac arrest if levels become too high. Because of this, ACE inhibitors are generally not given with potassium-sparing diuretics or potassium supplements.

ACE inhibitors can harm a developing fetus and should not be used during pregnancy.

[For more information on blood pressure drugs, see In-Depth Report #14: High blood pressure.]

• 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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