A Statin Alternative Lowers Heart Attack Risk by 23 Percent, Drug Trial Shows
Nexletol is a new option for the millions of people in the United States who discontinue statin therapy within a year.
Bempedoic acid (Nexletol), a cholesterol-lowering drug intended for people who can’t or won’t take statins, was shown to reduce the risk of heart attack by 23 percent, according to a late-breaking clinical trial recently presented at the American College of Cardiology Conference and published online March 4 in the New England Journal of Medicine.
“These findings add bempedoic acid to the group of LDL cholesterol lowering medications that have shown clinically meaningful cardiovascular benefits,” said the study’s first author, Steven Nissen, MD, the chief academic officer of Cleveland Clinic’s heart, vascular, and thoracic institute, in a press release.
People who are unwilling or unable to take statins have limited options for other cholesterol-lowering medications. One possible choice is bempedoic acid, which was approved by the U.S. Food and Drug Administration (FDA) in 2020. In early clinical trials, bempedoic acid was shown to lower LDL “bad” cholesterol by 15 to 25 percent, and by 38 percent when combined with ezetimibe (Nexlizet), but its effects on clinical outcomes such as heart attack and stroke had not been studied.
The new research, part of an initiative called the CLEAR Outcomes trial, establishes bempedoic acid as an effective approach to lowering LDL cholesterol and reducing the risk of cardiovascular events like heart attack or stroke.
Is Bempedoic Acid as Effective as Statins?
It’s worth noting that Nexletol lowered LDL-cholesterol levels only about 20 percent more than placebo at six months, says Wesley Milks, MD, a cardiologist and a clinical assistant professor of internal medicine at the Ohio State Wexner Medical Center in Columbus, Ohio. Dr. Milks is a site co-investigator for the CLEAR Outcomes trial, in which the Ohio State University Wexner Medical Center participated.
In contrast, Milks says that high-intensity statin therapy can bring down LDL cholesterol by 50 percent or more, and generally does more to reduce the risk of ASCVD (atherosclerotic cardiovascular disease) than non-statin medications for a given amount of cholesterol reduction.
Up to 29 Percent of People Say They Can’t Tolerate Statins
The CLEAR Outcomes findings support bempedoic acid as an effective therapy for the 7 to 29 percent of patients who report so-called statin intolerance, said Nissen.
Doctors have recommended statins to more than 40 million adults in the United States, according to estimates, making this class of drugs one of the most prescribed in the country. But even though statins have decades of safety and efficacy data behind them, many people decide never to fill the script.
On top of that, a sizable percentage of people who do take statins decide to stop: It’s estimated that between 40 and 75 percent of people discontinue therapy within their first year.
The most cited reason for not taking a statin is potential side effects, specifically muscle pain or aching, and stiffness or cramps.
Bempedoic Acid May Be Less Likely Than Statins to Cause Muscle Pain
According to the study authors, bempedoic acid works in the liver, lowering cholesterol by inhibiting an enzyme called adenosine triphosphate citrate lyase (ACLY).
Because the medication is activated in the liver rather than in the muscle or other tissues, it may be less likely to cause the muscle-related side effects experienced by some patients on statins, wrote the authors.
Nexletol Lowered the Risk of Any Major Cardiac Event
The clinical trial involved almost 14,000 adults who took either a daily bempedoic acid pill or a placebo. The research was funded by Esperion, the pharmaceutical company that produces the drug.
All participants had a history of cardiovascular issues or were assessed to be at high risk for a cardiovascular crisis. All were “statin-intolerant,” meaning they had used statins at some point and stopped because of an issue that began or increased during treatment and disappeared or improved once they stopped taking the drug.
At the end of six months, the group who took Nexletol saw their LDL levels drop by an average of 29.2 points. The participants were followed (median follow-up of 40.6 months) to see how the medication changed their risk of cardiac events.
In addition to reducing the risk of a heart attack, the drug lowered the risk of a person needing cardiac revascularization (treatments that restore blood flow to the heart after some type of blockage) by 19 percent and showed a relative risk reduction of 13 percent for any major cardiac event.
The study also showed statistically significant reductions in death from all cardiovascular causes.
Nexletol Has a Very Good Benefit-to-Risk Ratio
“Bempedoic acid showed good safety, and its benefit-to-risk ratio was very good,” said Nissen in the press release. Rates of muscle-related complaints were similar between trial subjects who took the drug and those on placebo.
The study did show that people taking Nexletol had significantly higher rates of elevated uric acid and gout, as well as cholelithiasis (gallstones), which could suggest that this medication may not be the best option for people with these conditions, says Milks.
