What cholesterol medications are available?
Sometimes positive changes in diet, lifestyle and exercise are not enough. In these cases, doctors may consider the use of medication that lowers cholesterol. The decision to have a patient begin medication is often based on high levels of LDL cholesterol and other risk factors for cardiovascular disease. For example, medication may be indicated if your low-density lipoprotein level is over 190 or is over 160 and you have several other risk factors for cardiovascular disease. Drugs that reduce LDL blood levels can prevent or reduce the build-up of artery blocking plaques and can limit the possibility of the release of those plaques as dangerous blood clots. Different types of cholesterol-reducing drugs work in different ways. Not all cholesterol comes from the diet -- some is made in the body. So the strategy of some drugs is to prevent the body from making cholesterol. Other cholesterol-reducing drugs interfere with the body's ability to absorb cholesterol from food. A third approach involves drugs that combine with cholesterol and remove it from the bloodstream. Examples of cholesterol-reducing drugs are cholestyramine (Questran), colestipol (Colestid), gemfibrozil (Lopid), lovastatin (Mevacor), pravastatin (Pravachol) and simvastatin (Zocor). Lovastatin, pravastatin and simvastatin belong to a group of medicines called HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors. These drugs prevent the body from making cholesterol by blocking a key enzyme in the process.
There are several types of drugs that can help reduce blood cholesterol levels, including:
Staitins : Statins lower low-density lipoprotein cholesterol levels more than other types of drugs. Statins inhibit an enzyme, HMG-CoA reductase, that controls the rate of cholesterol production in the body. These drugs lower cholesterol by slowing down the production of cholesterol and by increasing the liver's ability to remove the low-density lipoprotein cholesterol already in the blood.
Statins were used to lower cholesterol levels in many of the clinical trials discussed previously. The large reductions in total and LDL cholesterol produced by these drugs resulted in significant reductions in heart attacks and coronary heart disease deaths. Thanks to their safety and to their ability to lower low-density lipoprotein cholesterol the number of coronary heart attacks and heart disease deaths, statins have become the drugs most often prescribed for lowering cholesterol.
Studies using statins have reported 20-60% lower LDL cholesterol levels in people taking them. Statins also reduce high triglyceride levels modestly and produce a mild increase in HDL cholesterol. The statins are most often given in a single dose at the evening meal or at bedtime. It is important that these medications be given in the evening to take advantage of the fact that the body makes more cholesterol at night than during the day. Newer, long-acting statins, such as atorvastatin (Lipitor), may be administered in the morning.
You should begin to see results from the statins after several weeks, with a maximum effect in 4-6 weeks. After about 6-8 weeks, your doctor can do the first check of your LDL cholesterol while you are on the medication. A second measurement of your low-density lipoprotein cholesterol level must be averaged with the first for your doctor to decide whether your dose of medicine should be changed to help you meet your goal.
The statins are well tolerated, and serious side effects are rare (liver problems, muscle soreness, pain, weakness). If this happens, or if you have brown urine, contact your doctor right away to get blood tests for possible muscle problems. Rarely, widespread muscle breakdown, known as rhabdomyolysis, can occur, usually in people who are taking other drugs that interfere with the breakdown of the statin and in people with advanced kidney problems. This is a medical emergency. So, if you have diffuse muscle pain and weakness, or brown urine (a possible sign of muscle breakdown), contact your doctor immediately and stop taking the statin medication. Some people experience an upset stomach, gas, constipation, and abdominal pain or cramps. These symptoms are usually mild to moderate and generally go away as your body adjusts. Monitoring of liver function tests is usually done in patients taking statins.
Niacin : The B vitamin Niacin, in high doses, can lower triglycerides and low-density lipoprotein levels and increase HDL levels. Niacin has been proven to reduce a person's risk of having a second heart attack.
Nicotinic acid or niacin: This water-soluble B vitamin improves all lipoproteins when given in doses well above the vitamin requirement. Nicotinic acid lowers total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels, while raising HDL cholesterol levels.
There are 2 types of nicotinic acid: immediate release and extended release. The immediate-release form of crystalline niacin is inexpensive and widely accessible without a prescription, but, because of potential side effects, it must not be used for cholesterol lowering without the monitoring of a doctor. (Nicotinamide, another form of niacin, does not lower cholesterol levels and should not be used in place of nicotinic acid.) If you take nicotinic acid to lower cholesterol, your doctor will closely monitor you to avoid complications from this medication. You should not take this medication on your own. You may miss important side effects. Nicotinic acid reduces LDL cholesterol levels by 10-20%, reduces triglycerides by 20-50%, and raises HDL cholesterol by 15-35%.
A common and troublesome side effect of nicotinic acid is flushing or hot flashes, which are the result of blood vessels opening wide. Most people develop a tolerance to flushing, which can sometimes be decreased by taking the drug during or after meals or by the use of aspirin or other similar medications prescribed by your doctor 30 minutes prior to taking niacin. The extended-release form may cause less flushing than the other forms.
The effect of high blood pressure medicines may also be increased while you are on niacin. If you are taking high blood pressure medication, it is important to set up a blood pressure monitoring system while you are getting used to your new niacin regimen. A variety of gastrointestinal symptoms, including nausea, indigestion, gas, vomiting, diarrhea, and the activation of peptic ulcers, has been seen with the use of nicotinic acid. Three other major adverse effects include liver problems, gout, and high blood sugar. Risk of the latter 3 complications increases as the dose of nicotinic acid is increased. Your doctor may not prescribe this medicine for you if you have diabetes because of the effect on your blood sugar.
Extended-release niacin is often better tolerated than crystalline niacin. However, its liver toxicity (liver damage) is probably greater. Therefore, the dose of extended-release niacin is usually limited to 2 grams per day.
Bile acid sequestrants : These drugs bind with cholesterol-containing bile acids in the intestines and are then eliminated in the stool. The usual effect of bile acid sequestrants is to lower low-density lipoprotein cholesterol by about 10-20%. Small doses of sequestrants can produce useful reductions in low-density lipoprotein cholesterol.
Bile acid sequestrants are sometimes prescribed with a statin to enhance cholesterol reduction. When these drugs are combined, their effects are added together to lower low-density lipoprotein cholesterol by more than 40%.
Cholestyramine (Questran, Questran Light), colestipol (Colestid), and colesevelam (Welchol) are the 3 main bile acid sequestrants currently available. These 3 drugs are available as powders or tablets. They are not absorbed from the gastrointestinal tract, and 30 years of experience with these drugs indicates that long-term use is safe.
Bile acid sequestrant powders must be mixed with water or fruit juice and must be taken once or twice (rarely, 3 times) daily with meals. Tablets must be taken with large amounts of fluids to avoid stomach and intestinal problems. Sequestrant therapy may produce a variety of symptoms, including constipation, bloating, nausea, and gas. The bile acid sequestrants are not prescribed as the sole medicine to lower your cholesterol if you have high triglycerides or a history of severe constipation. Although sequestrants are not absorbed, they may interfere with the absorption of other medicines if taken at the same time. You must take other medications at least 1 hour before or 4-6 hours after the sequestrant. You should talk to your doctor about the best time to take this medicine, especially if you take other medications.
Cholesterol absorption inhibitors : This new class of drugs was approved in late 2002. The drug inhibits cholesterol absorption in the gut and has few, if any, side effects. Cholesterol absorption inhibitors may rarely be associated with tongue swelling (angioedema). Ezetimibe (Zetia) is the first drug in this class. Ezetimibe reduces LDL cholesterol by 18-20%. It is probably most useful in people who cannot take statins or as an additional drug for people who take statins but who notice side effects when the statin dose is increased. Adding ezetimibe to a statin is equivalent to doubling or tripling the statin dose.
Fibrates : These cholesterol-lowering drugs are primarily effective in lowering triglycerides and, to a lesser extent, increasing HDL cholesterol levels. Gemfibrozil (Lopid), the fibrate most widely used in the United States, can be effective for people with high triglyceride levels. However, gemfibrozil is not very effective for lowering LDL cholesterol. It is used in some people with heart disease for whom a goal of treatment is lowering triglycerides or raising HDL. Another fibrate is fenofibrate (Tricor), which is more effective at lowering triglycerides and low-density lipoprotein cholesterol. Some people taking fibrates may have side effects such as stomach or intestinal discomfort. Fibrates may increase the likelihood of your developing gallstones and can increase the effect of medications that thin the blood. Your doctor will monitor you. The dose of fibrates should be reduced if your kidney function declines.
Hormone replacement therapy : The risk of heart disease is increased in women after menopause. The increasing risk may be related to loss of estrogen that comes with menopause. Previously, women might have been treated with hormone replacement therapy (replacing the estrogen and perhaps progestin). Recent studies have found that women on hormone replacement therapy did not benefit by having a lower rate of heart-related events compared with women treated with placebo.
Therefore, postmenopausal women who are judged by their doctor to need drug treatment to reduce their risk for heart disease should consider cholesterol-lowering drugs instead of hormones because cholesterol-lowering drugs have been shown to be safe and effective in lowering cholesterol and reducing coronary heart disease risk.