For the roughly 94 million Americans with high cholesterol, 90 percent are prescribed a class of drugs called statins. These drugs help lower low-density lipoprotein (LDL)—commonly called the “bad” cholesterol—in the blood, but can trigger muscle pain, increase blood sugar or occurence of type 2 diabetes, and occasionally cause liver damage or neurological issues. An estimated 10 to 30 percent of patients stop taking them due to these unwanted side effects.
However, a different medication already used around the world might be a solid alternative for those who can’t take statins. A large study published on March 4 in the New England Journal of Medicine found that bempedoic acid can lower LDL levels by 21.7 percent.
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While statins are considered both safe and effective, they don’t work for everyone. In 2020 the Food and Drug Administration approved bempedoic acid—sold under the brand name Nexletol—to treat patients who can’t or won’t take statins. There was a lack of data from randomized controlled trials on the drug’s effects on heart health, despite studies showing it could lower LDL by 17 to 28 percent. The new research was funded in part by Esperion Therapeutics, the Michigan-based maker of Nexletol.
Bempedoic acid works by drawing cholesterol out of the waxy plaque that can build up in artery walls and interfere with blood flow, the same way that statins do. Too much plaque buildup can lead to strokes and heart attacks. According to the authors, bempedoic acid is activated in the liver and not the muscles, so it is unlikely to cause musculoskeletal pain the way statins can.
The study included 13,970 patients from 32 countries with an average age of 65 years old. Every participant had experienced musculoskeletal adverse effects from statins, and required alternative treatment. There were roughly the same number of men and women in the trial, but 91 percent were white and 17 percent were Hispanic or Latinx.
The participants were randomized into two groups: one took bempedoic acid and the other was given a placebo. The researchers followed up with the patients for up to five years and found that the drug was well-tolerated and reduced LDL cholesterol by 21.7 percent compared with the placebo. Additionally, the risk of cardiovascular events was 13 percent lower with bempedoic acid over a median of 3.4 years compared with the placebo. By comparison, some statins can lower LDL levels by as much as 50 percent.
According to the authors, the drug worked in patients who’d previously experienced a cardiovascular event or were at risk of a first event. The study also included multiple diabetics, and did not observe any blood-sugar increases from the treatment. There were a few more cases of gout and gallstones in the group that took bempedoic acid than in the placebo group, but one of the authors told CNN that lowering the risk of a heart attack outweighs a possible gout attack.
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In an editorial accompanying the study, John H. Alexander, the director of cardiovascular research at Duke Clinical Research Institute, wrote, “The benefits of bempedoic acid are now clearer. It is now our responsibility to translate this information into better primary and secondary prevention for more at-risk patients, who will, as a result, benefit from fewer cardiovascular events.”
However, proving that a medication can lower cholesterol does not automatically mean it will improve cardiac health. In 2020, a drug made by Eli Lilly called evacetrapib dramatically lowered LDL cholesterol, but doubled “good” high-density lipoprotein (HDL) and did not prevent heart attacks. The new bempedoic acid study was also not conducted long enough to get a sense of how many deaths it did or did not prevent.
The positive findings are just the first step in getting the statin alternative to be more widely accepted by physicians. The study’s co-author Steven Nissen, the chair of cardiovascular medicine at the Cleveland Clinic, told The Washington Post that unless there is critical “outcome data” showing that bempedoic acid reduces heart attacks, doctors are not as likely to prescribe the treatment and insurers may not cover it.
“In the current era where we have other cholesterol-lowering drugs, people are not going to use a drug that does not have demonstrated outcome benefits. People want evidence. Everybody has been waiting for this trial,” Nissen said.
NYU Langone Health cardiologist Howard Weintraub commented that while some will not consider a medication successful unless it reduces mortality, he believes that is short-sighted. “I think there’s more to doing medicine than counting body bags,” he told CNN. Weintraub was not involved in this specific study, but was pleased with the results, especially for those who could benefit from lowering cholesterol but can’t take statin medications. “Preventing things that can be life changing … and certainly change your quality of life forever going forward,” he said, “I think is a good thing.”