Pharmacological Therapy for Hypercholesterolemia

Prescription Image - Masterfile

The introduction of HMG-CoA reductase inhibitors (statins) has significantly advanced the treatment of hypercholesterolemia. Statins can reduce LDL cholesterol levels by 20–40 percent and, at maximum doses, they can lower levels by 40–50 percent. They also can modestly increase HDL ("good") cholesterol levels, usually by about 5–10 percent.

These medications are usually well tolerated, have few side effects, and are taken once or twice a day. Because the body produces cholesterol primarily during the night, these medicines usually are taken after dinner or during the evening. Higher doses can be split and taken once in the morning and once in the evening.


Commonly prescribed statins include the following:

  • Atorvastatin (Lipitor)
  • Fluvastatin (Lescol)
  • Lovastatin (Mevacol)
  • Pitavastatin (Livalo; approved in August 2009)
  • Pravastatin (Pravachol)
  • Rosuvastatin calcium (Crestor)
  • Simvastatin (Zocor)

Rare side effects associated with statins include mild inflammation of the liver, muscle inflammation, pain, and weakness. Inflammation of the liver can be detected by liver function tests, which usually are performed once or twice during the first several months of therapy and periodically (e.g., twice a year) thereafter. *This recommendation was modified by the FDA in February 2012. Patients who experience severe muscle pain or weakness or any uncomfortable side effect should speak with their physician.

Lipitor has been combined with the blood pressure-lowering drug Norvasc to treat patients with high cholesterol and high blood pressure. This combination drug, which is called Caduet, offers the convenience of taking only one medication to control both conditions.

In November 2011, the FDA approved atorvastatin calcium tablets—the first generic form of Lipitor. This medication, which has the same quality and strength of the brand name drug, is available four doses—10 mg, 20 mg, 40 mg and 80 mg. Side effects include diarrhea, joint pain, nasal inflammation and urinary tract infection (UTI).

The U.S. Food and Drug Administration approved important safety revisions to statin labels in February 2012. Label changes include the following:

  • A recommendation that patients undergo liver enzyme tests prior to beginning statin therapy and then as clinically indicated thereafter has been added. (Previous labeling recommended periodic liver enzyme monitoring for all patients taking statin drugs.)
  • Information about possible reversible cognitive changes, such as memory loss and confusion, and increased blood glucose levels while on statin therapy has been added.
  • Information about the contraindications and dosing instructions for lovastatin (Mevacol) has been updated.

Other Medications to Treat High Cholesterol

Other cholesterol-lowering medications can be used alone, or combined with a statin, to reduce cholesterol to an acceptable level. Combining medications may increase the risk for liver and/or muscle inflammation.

Other medications include the following:

  • Cholestyramine (LoCHOLEST, Questran)
  • Colestipol (Colestid)
  • Fenofibrate (Tricor)
  • Fluvastatin (Lescol)
  • Gemfibrozzil (Lopid)
  • Niacin (Niacinol, Niacor, Nicolar, Slo-Niacin)

In December 2012, the FDA approved a new medication to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in people with a rare cholesterol disorder called homozygous familial hypercholesterolemia (HoFH). This medication, called lomitapide (Juxtapid), is intended for use in combination with a low fat diet and other lipid-lowering treatments.

Although HoFH affects only one in 1,000,000 people in the United States, heart attack and death are common in people with the disorder—often before the age of 30. Lomitapide is a capsule that is taken once per day, without food and at least two hours after the last meal of the day. This medication blocks the absorption of fat-soluble nutrients, so patients are advised to take daily supplements that contain fat-soluble vitamins and essential fatty acids while taking lomitapide.

It carries a Boxed Warning due to a serious risk of liver toxicity, and can lead to progressive liver disease with chronic use. Lomitapide also interacts with several other medications. Common side effects include abdominal pain, diarrhea, nausea, vomiting and indigestion.

Another medication—mipomersen sodium (Kynamro)—was approved by the FDA in January 2013 to treat HoFH. This medication is administered by injection given once per week. It is also used in combination with lipid-lowering medications and lifestyle measures. Kynamro carries a Boxed Warning due to a serious risk for liver toxicity. Common side effects include injection site reaction, flu-like symptoms, nausea and headache. Kynamro can cause elevated liver enzymes. Additional studies are ongoing.

Alirocumab (Praluent injection) and evolocumab (Repatha)—the first and second medications in a class of drugs called proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors—were approved in July and August 2015 respectively. These medications are used in addition with diet and statin therapy in adults with heterozygous familial hypercholesterolemia (HeFC) and adults with clinical atherosclerotic heart disease (e.g., heart attack, stroke) who need to lower LDL further. Repatha also can be used in adults with HoFH.

Praluent and Repatha target a specific protein (PCSK9), which reduces the number of receptors in the liver that work to remove LDL cholesterol from the blood. As of July 2015, clinical trials evaluating the risks/benefits of adding Praluent to statin therapy to reduce cardiovascular disease is ongoing.

Side effects of Praluent and Repatha include itching, swelling, pain, or bruising at the site of the injection, nasal congestion, and flu-like symptoms. Severe allergic reactions also may occur with both drugs.

Updated by Remedy Health Media

Publication Review By: Stanley J. Swierzewski, III, M.D.

Published: 30 Jun 2000

Last Modified: 31 Aug 2015