Clinical Question

Is bempedoic acid (Nexletol) effective for the primary prevention of cardiovascular disease?

Evidence-Based Answer

Bempedoic acid can be used to effectively treat hyperlipidemia. (Strength of Recommendation [SOR]: B, single, high-quality, randomized controlled trial [RCT].) Bempedoic acid decreases the incidence of major adverse cardiovascular events, with insignificant increases in liver enzyme and creatine kinase levels, gout, myalgia, and cholelithiasis. When bempedoic acid is used for the primary and secondary prevention of cardiovascular disease, it is more effective than placebo at lowering non–high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol. (SOR: C, disease-oriented evidence based on a single meta-analysis of RCTs.) In patients prescribed a maximum dosage of tolerated statins, bempedoic acid added to ezetimibe, compared with either agent alone, is more effective at lowering LDL cholesterol. (SOR: C, disease-oriented evidence based on a single RCT.)

Evidence Summary

A 2023 subgroup analysis of a double-blind RCT evaluated the benefit of bempedoic acid (180 mg) vs. placebo for primary cardiovascular disease prevention in patients with statin intolerance.¹ The subgroup analysis included 4,206 patients (59% were female between 18 and 85 years of age; 92% identified as White) who met the criteria for high cardiovascular risk without a previous cardiovascular event and intolerance to the guideline-recommended dosage of statins. Most patients had diabetes mellitus (66%) or hypertension (88%). Patients were permitted to continue adjunct antihyperlipidemic agents; 19.3% took a very low-dose statin (defined as less than 10 mg daily of simvastatin or atorvastatin), and 8% took ezetimibe. The primary outcome was the time to first incidence of a four-component major adverse cardiovascular event (i.e., death from cardiovascular cause, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization).