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Dec 13, 2023

A new report suggests that moderate-intensity statins, a drug used to reduce cholesterol in people at risk for cardiovascular disease, combined with ezetimibe, another type of cholesterol-lowering medication, may be just as effective as high-intensity statins.

The study, published in JAMA Cardiology on Wednesday, found taking a lower dose of the statin rosuvastatin (known by the brand name Crestor) alongside ezetimibe (known by the brand name Zetia) can be just as helpful as a higher dose of rosuvastatin when it comes to preventing cardiovascular deaths, hospitalization for cardiovascular events, and strokes.

The combination therapy is frequently used in patients — particularly with those who experience statin side effects like muscles aches — and is well tolerated.

“These results are consistent with prior work showing that anything that lowers LDL-cholesterol will reduce risk. In this case, the combination therapy of lower dose rosuvastatin plus ezetimibe was a little more effective in lowering LDL-cholesterol and had slightly fewer side effects,” Dr. Joshua Knowles, MD, PhD, an associate professor of cardiovascular medicine at Stanford Health Care, told Healthline.

The researchers evaluated the health data of 1,511 people at a very high risk of atherosclerotic cardiovascular disease (ASCVD).

Atherosclerotic cardiovascular disease is heart disease that results from a build-up of a sticky substance called plaque in your arteries, according to the National Institutes of Health. The condition called atherosclerosis builds up slowly due to cholesterol, fats, and other substances. About half of adults between the ages of 45 to 84 in the U.S have atherosclerosis and are unaware of it.

The individuals in the study had taken part in a randomized clinical trial that was conducted between February 2017 and December 2018 in Korea.

Those at very high risk for heart disease included people who had a history of multiple major cardiac events or one major cardiac event in addition to other high-risk health conditions.

Adults with documented ASCVD were split into two groups: one that took a moderate-intensity statin combined with ezetimibe (10 milligrams of ezetimibe with 10 mg of rosuvastatin) and another group that took a high-intensity statin monotherapy (20 mg of rosuvastatin).

Rosuvastatin acts on the liver and inhibits cholesterol synthesis in liver cells while ezetimibe blocks absorption of cholesterol from the gut, reducing the amount of cholesterol that’s available to liver cells, says Knowles.

“By using both medications, physicians can target both the production and absorption of cholesterol,” Joyce Oen-Hsiao, MD, FACC, the director of clinical cardiology at Yale Medicine, said.

To measure the effectiveness of the two therapy options, the researchers evaluated the number of cardiovascular deaths, coronary or peripheral revascularizations, hospitalizations for cardiovascular events, and nonfatal strokes that occurred in the two patient groups within three years.

They found that, among people with a very high risk of cardiovascular disease, there was no significant difference between those who received combination therapy and those who took the high-intensity statin.

However, the median low-density lipoprotein cholesterol (LDL-C) level was much lower in the combination moderate-intensity statin group than in the high-intensity statin group.

The moderate-intensity statins were also associated with a greater mean change in LDL-C levels.

The researchers say their findings suggest that the ezetimibe-rosuvastatin combination is a useful treatment option for people at very high risk with ASCVD.

The 2018 American Heart Association (AHA)/American College of Cardiology (ACC) guidelines on lipid management recommend that people with a very high risk of ASCVD use high-intensity statins.

“Statins work to reduce risk because they lower LDL-cholesterol and since high-intensity statins — a high dose of a potent statin — lower LDL-cholesterol the most, they are the most effective in reducing risk,” says Knowles.

Past research has found that the prescription rate of high-intensity statins in the United States was the prescription rate of a high-intensity statin was 22.5% and nearly 50% of people at very high risk of heart disease weren’t taking high-intensity statins.

Many people are concerned about adverse effects, which have led to the underuse of high-intensity statins.

“Some of this is due to the ‘bad press’ that statins have received, some due to lack of medical access or education,” says Knowles.

Oen-Hsiao says statins are one of the most common medications that people ask to stop.

In certain cases, the medications can cause muscle aches and a slightly increased risk of diabetes.

“Sometimes, the muscle aches are so severe that it can affect patients physically, which can lead to a reduction in exercise,” said Oen-Hsiao.

According to Knowles, even in these cases, the medications still dramatically lower the risk of heart attack or stroke.

Knowles says the greatest “side effects” of taking high-intensity statins include a lower risk of heart attack, stroke, or the need for a procedure such as bypass surgery or cardiac catheterization with stent placement.

Oen-Hsiao says cardiologists often use the combination of moderate-intensity statins plus ezetimibe in people who are unable to tolerate high doses of statins — usually because of muscle aches or elevated liver function tests — to achieve the desired LDL goal.

Some people are able to tolerate a lower statin dose better, says Oen-Hsiao.

Prior research has shown this treatment combination to be similarly effective at preventing negative cardiovascular events as high-intensity statins in people with ASCVD.

This new paper solidified those findings and identified the same effect among people with a very high risk of ASCVD.

Many people require more than one medication to manage their cholesterol levels and heart disease risk.

By having multiple therapy options available, people can choose the type of treatment that aligns with their personal preferences.

“These decisions are nuanced and depend on patient preference, cost, side effects and other considerations,” says Knowles.

Moderate-intensity statins, a drug used to reduce cholesterol in people at risk for cardiovascular disease, combined with ezetimibe, another type of cholesterol-lowering medication, may be just as effective as high-intensity statins. Though high-dose statins are recommended for people with a very high risk of heart disease, many don’t take the medication because of adverse side effects associated with the drug. A lower dose, combined with ezetimibe, can be given to people at high-risk of heart disease who are concerned about the side effects.

A new study finds people at high risk for heart disease can still benefit from moderate-intensity statins.Heart disease is the top cause of death for both men and women in the U.S. Statins can help reduce cholesterol levels, but some people experience painful side effects including muscle aches.