Statins Alone Aren't the Only Option for High Cholesterol

High cholesterol may be treated with combination therapy instead of just a higher intensity statin

/ Author:  / Reviewed by: Joseph V. Madia, MD Beth Bolt, RPh

(RxWiki News) When unhealthy cholesterol hits very high levels, patients might take a statin medication to help reduce those levels. For those who don’t respond well to this treatment, a lower-intensity statin with another medication may help.

High levels of low-density lipoproteins (LDL), known as the "bad" cholesterol, can increase the risk of heart disease. Many doctors recommend lowering LDL by taking only a moderate- or high-intensity statin. Some patients, however, have a negative reaction to this therapy.

Scientists have recently found that some patients with high cholesterol may respond just as well to a lower-intensity statin combined with other types of cholesterol-fighting medication, specifically bile acid sequestrants or ezetimibe (brand name Zetia).

"Discuss treatment options for lowering cholesterol with your doctor."

Kimberly Gudzune, MD, assistant professor of medicine at Johns Hopkins University in Baltimore, Maryland, and her colleagues reviewed a total of 36 published trials of patients taking statin monotherapy or statins in combination with other treatment.

If LDL cannot be lowered with diet, exercise, weight loss and nutritional supplements, doctors often prescribe statins.

High-intensity statins may be given when LDL is 4.91 mmol/L (millimoles per liter) or greater, which is considered very high, according to the National Cholesterol Education Program. LDL levels less than 2.6 mmol/L are considered optimal.

Previous research has shown that two of the most commonly prescribed statins for intensive monotherapy are atorvastatin (brand name Lipitor) and rosuvastatin (brand name Crestor).

The intensity of statin therapy depends on the dose of medication and which statin is used. For example, 5 milligrams of atorvastatin per day is considered low intensity and 20 to 80 milligrams is considered high intensity.

While statins are generally well-tolerated, some patients experience adverse effects, including muscle pain and damage (myopathy), liver damage, digestive problems, rash or flushing, increased blood sugar or type 2 diabetes and memory loss or confusion.

Dr. Gudzune and team weighed the benefits and harms of taking a lower-intensity statin combined with another medication that would modify lipids. These other medications included bile acid sequestrants, ezetimibe, fibrates, niacin and w-3 fatty acid.

Looking at those who were at high risk for cardiovascular disease, these researchers found that lower-intensity statins combined with bile acid sequestrants or ezetimibe decreased LDL cholesterol at least as well as higher-intensity monotherapy. Data on adverse events, however, was limited.

Bile acid sequestrants and ezetimibe decrease cholesterol absorption in the intestines.

The authors noted that a low-intensity statin plus bile acid sequestrant decreased LDL cholesterol by 0 percent to 14 percent more than mid-intensity monotherapy among patients with abnormally high cholesterol.

Compared to high-intensity monotherapy, a mid-intensity statin given with ezetimibe decreased LDL cholesterol 5 percent to 15 percent more among patients with atherosclerotic cardiovascular disease. That same combo therapy lowered LDL 3 percent to 21 percent more among those with diabetes.

Dr. Gudzune and colleagues did not find sufficient evidence to compare monotherapy to combo therapy with fibrates, niacin and w-3 fatty acid.

"This study informs us that for patients who are intolerant of moderate to higher dose statin therapy for cholesterol reduction, treatment of bad cholesterol can be achieved through using a lower dose version of the statin in combination with other types of cholesterol-lowering medications," said Mohan Sathyamoorthy, MD, Chief of the Baylor All Saints Medical Center Cardiovascular Division.

"By doing so, cholesterol-lowering effects may be more significant. It is important to point out though that this study did not compare cardiovascular event rates between the two treatment strategies. Only you and your doctor can determine the best treatment strategy," Dr. Sathyamoorthy said.

Dr. Gudzune told dailyRx News, "Patients with LDL levels greater than 4.91 mmol/L are at great risk of cardiovascular disease and should have a discussion with their physician about how to decrease their disease risk. High dose statin monotherapy has demonstrated benefits with regards to lowering this risk, so this strategy should always be considered first."

"However, for patients who cannot tolerate high doses of these medications or do not respond to these medications, patients and physicians should weigh the LDL benefits by using combination therapy with lower intensity statin and bile acid sequestrant or ezetimibe."

This study was published online on February 11 in the Annals of Internal Medicine. Funding was provided by the Agency for Healthcare Research and Quality.

Review Date: 
February 10, 2014
Last Updated:
February 13, 2014