Research Summary

Bempedoic Acid Lowers Risk of Cardiovascular Events Among Those With Statin Intolerance

Anthony Calabro, MA

Cardiologists widely consider statins as the cornerstone of cardiovascular therapy1 because these medications decrease elevated levels of low-density lipoprotein (LDL) cholesterol and reduce the risk of major adverse cardiovascular events in patients with primary or secondary indications.

Although a foundational, go-to treatment option, reports2-4 indicate that 7% to 29% of patients have adverse musculoskeletal effects from statins. These patients are either prevented from taking statins or are severely limited in receiving guideline-recommended doses.

“Statin intolerance is a vexing clinical problem for which we have very limited options,” Steven E. Nissen, MD, cardiologist in the Department of Cardiovascular Medicine at the Cleveland Clinic in Cleveland, OH told Consultant360 in an interview.

But one of those options is bempedoic acid, a prodrug that is activated in the liver by the very-long-chain acyl-CoA synthetase-1 (ACSVL1) enzyme. Because bempedoic acid is activated in the liver and not in the muscles, it’s unlikely to cause the muscle-related adverse effects often associated with statins.

One study5 found that bempedoic acid can reduce LDL cholesterol by as much as 28%, which prompted approval for this indication by the FDA and European Medicines Agency. But the results in randomized clinical trials have been less clear.

Enter Dr Nissen and colleagues who conducted a double-blind, randomized, placebo-controlled trial to determine the effects of bempedoic acid on adverse cardiovascular events in patients who cannot tolerate statins.

Patients 18 to 85 years of age were eligible for the study if they either had a previous cardiovascular event or were considered high risk for a cardiovascular event. A total of 13,970 patients underwent randomization; 6992 patients were assigned to the treatment group and received oral bempedoic acid, 180 mg daily. The remaining 6978 patients were assigned to the placebo group.

The primary efficacy end point was a four-component composite of major adverse cardiovascular events (MACE): death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. The key secondary endpoints included a three-component composite of MACE (death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction), fatal or nonfatal myocardial infarction, coronary revascularization, fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause.

Among those patients who could not tolerate statins and whose primary or secondary prevention of cardiovascular disease was clinically indicated, the risk of a primary endpoint event decreased by 13% with bempedoic acid compared with placebo after a median of 40.6 months of follow-up. Bempedoic acid showed beneficial results compared with placebo when looking at the secondary endpoints as well.

“The risk of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (the first key secondary endpoint) was 15% lower with bempedoic acid than with placebo, and the risks of fatal or nonfatal myocardial infarction and coronary revascularization were 23% lower and 19% lower, respectively,” the authors wrote.

This study did have limitations. For example, the authors included only those patients who reported that they were unable or could not tolerate statins. This resulted in a high mean LDL cholesterol level at baseline.

Still, Dr Nissen believes these results will have far-reaching implications, even for specialists outside of cardiology.

“Everybody who treats patients with high LDL and has cardiovascular risk will be interested in these results,” Dr Nissen told Consultant360. “That includes primary practice physicians and internists. Indeed, it’s not just cardiologists who treat cholesterol. It's many different practitioners. In fact, in women, a lot of the people who treat their cholesterol are obstetrics & gynecology physicians. So they will be interested in these results as well.”

Want more expert perspective? Read our full Q&A interview with lead author, Steven E. Nissen, MD.


1.      Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023;10.1056/NEJMoa2215024. doi:10.1056/NEJMoa2215024.

2.     Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy — European Atherosclerosis Society Consensus Panel statement on assessment, aetiology and management. Eur Heart J. 2015;36:1012-1022.

3.     Bytyçi I, Penson PE, Mikhailidis DP, et al. Prevalence of statin intolerance: a meta-analysis. Eur Heart J. 2022;43:3213-3223.

4.     Hovingh GK, Gandra SR, McKendrick J, et al. Identification and management of patients with statin-associated symptoms in clinical practice: a clinician survey. Atherosclerosis. 2016;245:111-117.

5.     Ballantyne CM, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis. 2018;277:195-203.