Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients
Clinical question: Are there alternatives to statins for primary prevention?
Background: Statins that lower low-density lipoprotein (LDL) cholesterol are major therapeutics in reducing both primary and secondary risks of cardiovascular events. However, up to 29% of patients report intolerance, most commonly myalgias. Bempedoic acid is an adenosine triphosphate citrate lyase inhibitor targeting the cholesterol synthesis pathway. It reduces cholesterol production and helps clear LDL cholesterol in circulation. It is a prodrug that is activated in the liver and not in peripheral muscle, which helps to reduce the risk of adverse muscle effects.
Study design: Masked, randomized, clinical trial
Setting: 32 countries (including the U.S., Russia, Germany, Poland, South Africa, Canada, Türkiye, Mexico, Spain, Colombia, Australia, and the U.K.) with 1,250 participating sites
Synopsis: In this study, 4,206 primary prevention patients were randomized to receive bempedoic acid 180 mg orally daily versus placebo for the primary prevention of cardiovascular events. After an average of four years, they found a statistically significant reduction in high-sensitivity CRP level by 0.34 mg/L in the treatment group compared with a reduction of 0.01 mg/L in the control group. Significant reductions in cardiovascular death, nonfatal myocardial infarction, and stroke were found.
Some interesting limitations are that 66% of the patients overall had diabetes mellitus, the majority of the patients were from Eastern Europe, 58% were females, and the average LDL was around 142.5 mg/dL. Therefore, results might be exaggerated due to higher baseline LDLs. Side effects mentioned were liver function test elevations, acute kidney injury, elevated uric acid levels, gout, and cholelithiasis.
Bottom line: In patients who are statin intolerant, bempedoic acid is a medication to consider for the primary prevention of cardiac events. However, more randomized controlled trials are needed to determine the actual risk reduction, especially in non-diabetics.
Citation: Nissen SE, et al. Bempedoic acid for primary prevention of cardiovascular events in statin-intolerant patients. JAMA. 2023;330(2):131–140. doi:10.1001/jama.2023.9696.
Dr. Shahatto is a hospitalist in the division of hospital medicine and an assistant clinical professor in the department of medicine at UC San Diego Health at the University of California in San Diego.