Cleveland Clinic-Led Trial Shows That The First Drug Designed for Statin-Intolerant Patients Reduces Serious Cardiovascular Events

Findings from a Cleveland Clinic-led clinical trial showed that the use of bempedoic acid (a cholesterol-lowering drug) in statin-intolerant patients lowered low-density lipoprotein (LDL) cholesterol and reduced heart attacks and coronary procedures.

Findings were presented today during a Late Breaking Science Session at the American College of Cardiology’s 72nd Annual Scientific Session in New Orleans and simultaneously published in the New England Journal of Medicine.

Elevated LDL cholesterol can accumulate in the walls of blood vessels, creating blockages and raising the risk of heart attack or stroke. Statins are the standard first-line treatment for the prevention of cardiovascular disease and work by lowering cholesterol levels in the blood. Statins have been shown in many studies to reduce the risk of stroke, heart attack and death when administered to patients, both with a history of cardiovascular disease and without. However, some patients struggle with adverse side effects like muscle pain, headaches or weakness that prevent them from using statins at recommended doses.

Bempedoic acid is approved by the U.S. Food and Drug Administration as an additional treatment to help lower cholesterol in patients with certain conditions who have high cholesterol despite maximally tolerated statin therapy. The trial, called CLEAR Outcomes, is the first to explore whether bempedoic acid could reduce cardiovascular outcomes.

The study enrolled 13,970 statin-intolerant patients between December 2016 and August 2019 at 1,250 sites in 32 countries. To participate, patients and their physicians were required to confirm that the patient could not tolerate statins. All participants had LDL-c levels of 100 mg/dL or higher and either a previous cardiac event or other risk factors for heart disease. Participants were randomly assigned to take 180 mg of bempedoic acid or a placebo daily and followed for an average of over 3 years. The primary outcome studied was a composite of cardiovascular death, heart attack, stroke or coronary revascularizations (a procedure to open blocked arteries).

The primary outcome was reduced 13% with bempedoic acid treatment. When different types of cardiac events were analyzed separately, bempedoic acid was found to reduce heart attacks by 23% and coronary revascularizations by 19%.

“Until now, there have not been any drugs designed specifically for statin-intolerant patients,” said the study’s lead author Steven E. Nissen, MD, chief academic officer of the Heart Vascular & Thoracic Institute at Cleveland Clinic. “While statins remain the cornerstone of risk reduction in patients with elevated LDL cholesterol, this is a major step forward for a population who need statins but suffer troublesome side-effects.”

Bempedoic acid differs from statins by not activating until it reaches the liver. This limits the drug’s effects on muscle, or other tissues or organs, reducing the likelihood of side effects reported with statins.

Researchers note that the 20-25% reduction in LDL cholesterol reported for bempedoic acid is less than the 40-50% reductions typically achieved with statins. “Overall, these results reveal bempedoic acid can still make a significant difference in the risk of serious cardiac events for patients who cannot tolerate statins,” said Dr. Nissen.

The study was funded by Esperion Therapeutics, developer of bempedoic acid.

Dr. Nissen has served as a consultant for many pharmaceutical companies and has overseen clinical trials for AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Novartis, Mineralys, Silence Therapeutics, and Pfizer. However, he does not accept honoraria, consulting fees or other compensation from commercial entities.