Peripheral Artery Disease and Intermittent Claudication

Description

Alternative Names

Reducing Heart Risk Factors

Many experts now recommend that PAD patients be given the optimal treatments for managing any heart risk factors as well as treatments for intermittent claudication. Some require medications if they cannot control these risk factors with lifestyle measures. Specific medications may be better than others for PAD patients.

Statins and Treatment for Unhealthy Cholesterol and Lipid Levels

Aggressively controlling cholesterol levels is known to reduce mortality rates in patients with peripheral artery disease. Unhealthy cholesterol levels are major contributors to atherosclerosis, the common factor in heart disease and peripheral artery disease. Many experts now recommend that patients with PAD receive lipid-lowering treatment, just as patients do who have atherosclerosis in the heart arteries.

A number of drugs are available for lowering cholesterol. Those discussed in this report may be particularly beneficial for PAD patients. Statins, for example, may have additional advantages for patients with PAD, regardless of cholesterol levels.

Other useful cholesterol-lowering agents are fibrates and nicotinic acid, which are important agents for people who need to lower triglycerides and increase HDL. In fact, some evidence suggests that this lipid imbalance may be a more important factor for PAD than high-LDL cholesterol. In fact, combinations of such drugs with statins may be particularly beneficial.

Statins. Statins are the most effective drugs for the treatment of high cholesterol, and may even become important agents for many people at risk for heart disease who have normal cholesterol levels or below. Statins inhibit the liver enzyme hMG-CoA reductase, which is used in the manufacturing of cholesterol. Statins are particularly effective for lowering LDL levels. They also reduce triglycerides, apparently in direct proportion to their LDL-lowering effects. Statins also raise HDL levels, but to a lesser extent than other anti-cholesterol drugs.

Statins include lovastatin (Mevacor), pravastatin (Pravachol), and simvastatin (Zocor). These are the most studied statins and have proven effectiveness and good safety record. Newer, synthetic statins include fluvastatin (Lescol) and atorvastatin (Lipitor).

Statins effectively reduce the risk of heart attack and stroke in both women and men and in adults at any age (including the elderly) with unhealthy cholesterol levels. They may have similar benefits even in statin users, including PAD patients, who are at high risk for heart disease, even if they had normal or low cholesterol levels.

Of note, evidence now strongly suggests that statins have specific benefits for patients with PAD, including improving symptoms of intermittent claudication. In a 2003 study, for example, statin use was associated with improved leg function, regardless of the patients' cholesterol levels.

• Statins improve the function of the endothelium--the lining of blood vessels, thereby improving blood flow. (Oddly, this benefit apparently does not extend to people with diabetes.)
• 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 may help curtail blood clotting, a major factor in heart attacks.
• Some evidence suggests that they might promote growth of new blood vessels and might help prevent intermittent claudication.

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

The primary safety concern with statins has involved an uncommon condition called myopathy, which can cause muscle damage and in some cases, muscle and joint pain. The risk for myopathy is highest at higher doses and in older people, those who are small or frail, people who abuse alcohol, and those who are hypothyroid. There is also a higher risk if statins are used before surgery, and if people are taking multiple medications.

Statins also can effect the liver, particularly at higher doses, so periodic liver function tests should be administered. Statins should not be taken by anyone with liver problems or by women during pregnancy or breast-feeding. It should be noted that no studies have reported liver failure from statins, even in people with liver disease.

There have also been a few reports of peripheral neuropathy in patients taking statins. This condition causes sensation changes in the limbs, fingers and toes, including numbness, tingling, or pain.

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 lower cholesterol than the Lopid. Most fibrates have been shown to lower the risk of heart attack. They may have the following benefits for PAD patients:

• They are good choices for many patients who need to lower triglyceride levels and increase HDL but who cannot take nicotinic acid
• A study on fenofibrate further suggested that it reduced certain clotting factors (another risk factor for heart disease) and also uric acid (a risk factor for gout).

In one 2002 study, PAD patients who took bezafibrate experienced fewer non-fatal heart attacks and the severity of intermittent claudication was reduced. However, the drug had no effect on stroke.

Side effects 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 and substances including warfarin, some oral drugs used for diabetes, certain antibiotics, and grapefruit juice.

Nicotinic Acid (Niacin). Nicotinic acid is the active compound found in niacin, or vitamin B3. It raises HDL levels higher than any other anti-cholesterol drug and is the first choice for patients with low HDL levels. It is also extremely effective in reducing triglyceride levels. This agent then may have role for some patients with peripheral artery disease.

Brands include Niacor, Nicolar, and Slo-Niacin. An extended-release form (Niaspan), administered at bedtime, may have fewer side effects, including headaches and flushing, than rapidly-acting niacin agents. 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 physician's direction in order to ensure its safety and effectiveness. Combinations with other agents, particularly statins, may add significant benefits.

Many patients find its side effects intolerable, however. 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 usually occur between five minutes to hours after taking the drug and can last for minutes to, uncommonly, hours. The body does become tolerant to these effects eventually, and they generally subside. Gastrointestinal problems are common. Other side effects include dry skin and mucous membranes and darkening of the skin.

About 3% to 5% of people taking nicotinic acid develop liver abnormalities, which disappear after the medication is discontinued. The extended form (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 experience elevated levels in blood glucose, which could be a problem for people with diabetes. Niacin's effects on HDL and triglycerides, however, are especially suited for the lipid imbalances that are common in diabetes. And, some studies have reported that diabetics who use niacin had little trouble with glucose control.

ACE Inhibitors and Managing High Blood Pressure

People should aggressively control hypertension. Evidence suggests that the most protective agents for patients with high blood pressure and PAD may be angiotensin-convertingenzyme (ACE) inhibitors, which are described below.

Other important blood-pressure lowering agents are beta blockers and diuretics, calcium-channel blockers, and newer agents called angiotensin-receptor blockers (ARBs). Diuretics are low cost agents that have a proven track record for reducing mortality rates in most patient groups. Beta blockers potentially narrow blood vessels and are not ordinarily prescribed for patients with severe PAD.

Angiotensin Converting Enzyme Inhibitors. Angiotensin converting enzyme (ACE) inhibitors 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), and lisinopril (Prinivil, Zestril). ACE inhibitors are expensive, however, and the role for most people with high blood pressure may be limited. Nevertheless, they appear to be important agents for patients with peripheral artery disease and those with diabetes.

Side effects include an irritating cough, excessive drops in blood pressure, and allergic reactions. (In some people, the cough is intolerable. Iron supplements or the drug picotamide may prove to help reduce the frequency of coughs.) One rare but severe side effect, granulocytopenia, which is an extreme reduction in white blood cells, has been observed. In rare cases (0.3%), patients suffer a sudden and severe allergic reaction called angioedema that 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 action, they are not generally given with potassium-sparing diuretics or potassium supplements.

They can harm a developing fetus and should not be used during pregnancy, particularly in the second and third trimester.