Get answers to your heart disease prevention questions.
An in-depth report on the diagnosis, treatment, and prevention of unhealthy cholesterol levels.
Hypercholesterolemia; LDL; HDL; Triglycerides
Statins are the most effective drugs for the treatment of high cholesterol, particularly for lowering LDL levels. They also have modest effects in lowering triglycerides and increasing HDL levels. Statins inhibit the liver enzyme HMG-CoA reductase, which the body uses to manufacturer of cholesterol. These drugs effectively reduce the risk of major coronary events, including first and second heart attacks and stroke, in adults with unhealthy cholesterol levels.
Brands. Statins approved in the U.S. include:
Statins may also be prescribed as fixed-dose combination drugs, which combine two drugs in one pill:
Statins may be prescribed along with other cholesterol-lowering drugs, such as bile acid-binding resins, nicotinic acid (niacin), and fibrates.
Side Effects. Statins tend to be better tolerated than other cholesterol-lowering drugs Side effects may 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 is an uncommon condition called myopathy, in which a patient may experience muscle pains and certain lab tests may be elevated. A specific myopathy, called rhabdomyolysis, can lead to kidney failure, but fortunately its occurrence is very rare. The risk for myopathy/rhabdomyolysis is highest at higher doses and in older people (over 65 years), those with hyperthyroidism, and those with renal insufficiency (kidney disease). Both statins and fibrates carry a risk for myopathy. The combination of the two drugs increases this side effect. Some people who use a statin-fibrate combination withdraw from the regimen because of muscle discomfort.
In general, all statin therapy should start at a lower dose and be raised incrementally until healthy cholesterol levels are maintained. Patients should immediately tell their doctor about any unusual muscle discomfort or weakness, fever, nausea or vomiting, or darkening of urine color. Rosuvastatin (Crestor), may be associated with increased risk for myopathy and rhabdomyolysis, especially when given at the highest dose level (40 mg). The FDA advises that patients should not start therapy at a higher dose. In addition, people of Asian heritage appear to metabolize the drug differently and should start treatment at the lowest rosuvastatin dose (5 mg).
Statins can also affect the liver, particularly at higher doses, so patients should have periodic liver function tests. Anyone with liver problems and women who are pregnant or breastfeeding should not use statins. High doses of statins increase the risk for kidney failure, particularly for patients with other existing risk factors (diabetes, hypertension, atherosclerosis, history of heart failure).
Interactions with Drugs and Food. Statins may have some adverse interactions with other drugs, including other cholesterol-lowering medications. Among the drugs that increase the risk for adverse effects are cyclosporine, macrolide antibiotics, and certain antifungals. Patients should tell their doctors about any other medications they are taking. Grapefruit juice and Seville oranges may increase statin potency.
Brands. Nicotinic acid is the active compound found in niacin, or vitamin B3. It is a particularly helpful choice for patients with low HDL levels. 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 drugs. Although niacin is available over the counter, the active form used for cholesterol treatment is given in much higher doses. It is important to take this medication under a doctor's direction in order to ensure its safety and effectiveness.
Benefits. When used in high doses, niacin has the following benefits:
Combinations with other drugs, particularly statins, may add significant benefits.
Side Effects. Many patients do not like the side effects of the rapidly-absorbed form of niacin. About a quarter of patients who use 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 5 minutes to hours after taking the drug and can last for minutes to, uncommonly, hours. The body may eventually become tolerant to these effects, so they may diminish in time.
The following may reduce flushing and itching:
Stomach problems are common. Other side effects include dry skin and mucous membranes and darkening of the skin.
About 30% of patients who take niacin experience elevated levels in blood sugar (glucose), which can 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. Some studies report that people with diabetes who use niacin have little trouble with blood sugar control.
Potentially Serious Complications. About 3 - 5% of people taking niacin develop liver problems, which usually resolve 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 also avoid niacin because it elevates uric acid.
Brands. Fibrates (sometimes called fibric acid derivatives) break down the particles that make triglycerides. Gemfibrozil (Lopid, generic) is the standard fibrate. It is usually taken twice a day, 30 minutes before breakfast and before the evening meal. Other fibrates include fenofibrate (Tricor) and bezafibrate (Bezalip). They may be more effective in lowering cholesterol than gemfibrozil.
Benefits. Fibrates have the following effects on cholesterol, lipids, and other factors:
Side Effects. Side effects may include gastrointestinal discomfort, aching muscles, sensitivity to sunlight, and skin rashes. 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.
Drug Interactions. Fibrates interact with a number of drugs and substances, including warfarin, some oral drugs used for diabetes, certain antibiotics, and grapefruit juice.
Bile-acid binding resins work, as their name suggests, by binding to bile in the digestive tract. This reduces cholesterol in the following way:
Brands. Cholestyramine (Questran, Questran Light) is commonly used in a powder that is dissolved in liquid. Colesevelam (Welchol) is available in tablet form. Colestipol (Colestid) is another type of resin drug.
Side Effects. None of these drugs poses major risks. Most, however, cause constipation, heartburn, gas, and other gastrointestinal problems, side effects that many people cannot tolerate. Colesevelam, a newer resin, appears to have significantly fewer of these side effects.
Bile-acting drugs may contribute to calcium loss and therefore increase the risk for osteoporosis. Over time, deficiencies of vitamins A, D, E, and K may occur, and vitamin supplements may be necessary.
Bile acid binders can also elevate triglyceride levels. Rarely, toxic effects on the liver have been reported. Patients with liver disorders should be monitored.
Bile-acid binding resins may also interfere with the absorption of other medications, including digoxin (Lanoxin), thyroid replacement hormones, warfarin, beta-blocker drugs, and a number of medications used to treat low blood sugar. In order to prevent drug interactions, other drugs should be taken 1 hour before or 4 - 6 hours after taking the bile acid-binding resins.
Ezetimibe (Zetia) blocks absorption of cholesterol that comes from food. Ezetimibe is usually prescribed alone or in combination with a statin. Ezetimbe is also used in combination with fenofibrate (Tricor) for reduction of total cholesterol and LDL in patients with mixed hyperglycemia (high LDL levels, high triglycerides, low HDL levels) whose cholesterol has not been adequately controlled through diet alone.
Vytorin, is a combination of ezetimbe and the statin simvastatin into a single fixed dose pill. An important study found that combination does not protect arteries better than a statin alone. As a result, most doctors now reocmmend reserving ezetimbe for use as an add-on drug when statins do not achieve adequate LDL lowering. Vytorin should not be used along with fibrate drugs.
Lovaza is a prescription form of omega-3 fish oil, which may be prescribed to help lower triglyceride levels. Side effects include burping and a fishy taste. LDL levels may increase in some patients.
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