Treatment Options for High Blood Cholesterol

Cholesterol-Lowering Medications

The primary objective of drug therapy for people with high blood cholesterol is to lower the levels of low-density lipoprotein (LDL) or "bad" cholesterol sufficiently to reduce the risk of coronary artery disease. In general, the LDL cholesterol levels at which cholesterol-lowering medications are considered as an option are as follows:

  • People with existing coronary artery disease:

    • if the LDL cholesterol level is 130 mg/dL or higher
    • goal of drug therapy is to lower the LDL cholesterol level to 100 mg/dL or lower

  • People without coronary artery disease who have less than two risk factors:

    • if the LDL cholesterol level is 190 mg/dL or higher
    • goal of drug therapy is to lower the LDL cholesterol level to 160 mg/dL or lower

  • People without coronary artery disease who have two or more risk factors:

    • if the LDL cholesterol level is 160 mg/dL or higher
    • goal of drug therapy is to lower the LDL cholesterol level to 130 mg/dL or lower

The initial approach to lower LDL cholesterol levels is therapeutic lifestyle changes which include a cholesterol-lowering diet, weight loss, and a regular exercise program. If this approach fails to lower LDL cholesterol levels sufficiently, cholesterol-lowering medications can be considered. A variety of cholesterol-lowering medications are available that include:

  • Statins
  • Bile acid sequestrants
  • Nicotinic acid
  • Fibrates
  • Ezetimibe
  • Postmenopausal hormone therapy

Statins

Statins are medications belonging to a class of drugs known as hydroxymethyl glutaryl coenzyme A reductase inhibitors. Statins are the most commonly prescribed cholesterol-lowering medications. Statins work by blocking a substance that the liver needs to produce cholesterol and they also stimulate the liver to remove excess cholesterol from the bloodstream. In general, statins are the most effective cholesterol-lowering medications and can usually decrease LDL cholesterol levels by 20% to 60%.

Studies have shown that the statins reduce the risk of second heart attack and stroke in patients with proven cardiovascular disease (secondary prevention). The role of statins, however, in the primary prevention of heart attack and stroke in people without proven cardiovascular disease is far less certain and is still under investigation.

Current guidelines of the National Cholesterol Education Program Adult Treatment Panel III recommend the use of statins for primary prevention based on an individual's risk profile and LDL cholesterol levels. For patients with an LDL cholesterol level of less than 160 mg/dL, statin therapy is only recommended for those with diabetes or those with two or more cardiac risk factors and a 10-year risk for a first coronary artery disease event of at least 10%.

A recent meta-analysis of randomized, controlled clinical trials published in the Archives of Internal Medicine (Vol. 166, pp. 2307-2313; Nov. 27, 2006) evaluated the role statin therapy for the primary prevention of cardiovascular diseases in people without proven cardiovascular disease. Based upon the analysis of the data, the authors reached the following conclusions:

  • Statin therapy decreases the incidence of major coronary events (i.e., nonfatal heart attack) in people without known cardiovascular disease.

  • Statin therapy also decreases the incidence of major cerebrovascular events (stroke) in people without known cardiovascular disease.

  • Statin therapy does not reduce the risk of death from a fatal heart attack and does not reduce overall mortality from other causes in people without known cardiovascular disease.

Examples of specific statin medications that may be used to lower LDL cholesterol levels in the bloodstream include:

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

Adverse effects of statin drugs appear to be dose-related and tend to occur more frequently in patients taking higher doses of these medications. Adverse effects also tend to occur more frequently when statin drugs are used in combination with other cholesterol-lowering medications, such as niacin and fibrates. The most common side-effects of statin medications include non-specific muscles aches and pain that are reported to occur in about 5% of people. Elevated liver enzymes develop in up to 1% of people. The most serious adverse effect is a condition called rhabdomyolysis - a serious and potentially life-threatening condition involving destruction of skeletal muscles. Fortunately, this side-effect is rare with less than one death per million patients.

Bile Acid Sequestrants

Bile acid sequestrants are medications that are often prescribed along with statins to reduce levels of LDL cholesterol in the bloodstream. Bile acids are substances needed for digestion that are produced by the liver using cholesterol as a substrate. Bile acid sequestrants are medications that bind to bile acids which forces the liver to use more cholesterol to produce bile acids. The overall effect is a reduction in LDL cholesterol levels by about 10% to 20%.

Examples of bile acid sequestrants include:

  • Cholestyramine (Prevalite; Questran)
  • Colestipol (Colestid)
  • Colesvelam (WelChol)

Side-effects of bile acid sequestrants may include:

  • Bloating
  • Constipation
  • Gas
  • Nausea

Nicotinic Acid

Studies have shown that nicotinic acid or niacin lowers total cholesterol; lowers LDL cholesterol; and lowers triglyceride levels. It also increases the levels of HDL or "good" cholesterol. Although nicotinic acid is available over-the-counter, a prescription form of this product is also available (e.g., Niaspan). The prescription form of nicotinic is preferred and should be used under the care and supervision of a physician.

Possible serious side-effects of nicotinic acid may include:

  • Gout
  • High blood sugar
  • Liver problems
  • Stomach irritation

Fibrates

Fibrates are medications that can reduce triglyceride levels by as much as 20% to 50%, however, they are not very effective for reducing blood levels of LDL cholesterol. Fibrates can also increase levels of HDL cholesterol by up to 15%.

Examples of fibrates include:

  • Gemfibrozil (Lopid)
  • Fenofibrate (Lofibra; Tricor)

Side-effects of fibrates may include:

  • Elevated liver enzymes
  • Gallstones
  • Interaction with anticoagulant medications
  • Nausea

Ezetimibe

Ezetimibe (Zetia) belongs to a new class of cholesterol-lowering medications known as cholesterol absorption inhibitors. Ezetimibe lowers the levels of blood cholesterol by limiting the absorption of dietary cholesterol by the small intestine. The most common side-effects are back pain and joint pain. Ezetimibe may be used alone or it may be used in combination with a statin drug.

Vytorin is an example of a cholesterol-lowering medication that contains both a cholesterol absorption inhibitor (ezetimibe) and a statin drug (simvastatin). Vytorin was approved by the U.S. Food and Drug Administration (FDA)in 2004 and is indicated to reduce high LDL-cholesterol levels.

In November 2008, the FDA issued an early communication that it is investigating a possible association between the use of Vytorin and a potentially increased incidence of cancer. The FDA obtained preliminary data from a clinical trial known as the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) indicating that a larger percentage of test subjects treated with Vytorin died from all types of cancer when compared to subjects who were taking a placebo during the 5-year SEAS study.

The purpose of the SEAS study was to determine whether lowering LDL-cholesterol levels with Vytorin would reduce the risk of cardiovascular events (i.e., heart attack; stroke) in patients with aortic stenosis - a narrowing of the opening of the aortic valve in the heart. A lower overall cardiovascular risk was not found for subjects taking Vytorin during the study. A possible association between the use of Vytorin and a potentially increased incidence of cancer was an additional observation during the 5-year study period.

The FDA anticipates receiving a final SEAS study report in December 2008 and the Agency's review and evaluation of the clinical trial data is expected to take an additional 6 months. FDA will communicate its conclusions and recommendations at that time. In the meantime, health care professionals and caregivers should continue to monitor patients taking Vytorin and report side-effects from the use of this drug to the FDA.

This information reflects the FDA's current analysis of available data concerning Vytorin. Disseminating this information does not mean that FDA has concluded there is a causal relationship between Vytorin and cancer. Nor does it mean that FDA is advising health care professionals to discontinue prescribing Vytorin. FDA is considering but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this information when additional data becomes available.

Postmenopausal Hormone Therapy

In the past, hormone therapy (estrogen plus progestin) was used as a means of lowering cholesterol in many postmenopausal women. This practice, however, has been abandoned due to the results of more recent studies, particularly the Women's Health Inititative, which indicated that hormone therapy increases the risk of developing heart disease, breast cancer, and other complications.