Factors Associated With Enhanced Low‐Density Lipoprotein Cholesterol Lowering With Bempedoic Acid

BACKGROUND: Bempedoic acid (BA) inhibits ATP‐citrate lyase in the cholesterol synthesis pathway and lowers low‐density lipoprotein cholesterol (LDL‐C). As with other lipid‐lowering therapies, interindividual variation in response to BA was observed in clinical trials. We characterized LDL‐C response to BA using guideline‐defined statin intensity categories and identified clinical factors associated with enhanced LDL‐C lowering with BA. METHODS AND RESULTS: This post hoc analysis used pooled data from 4 phase 3 studies. Patients were randomized 2:1 to once‐daily BA 180 mg (n=2321) or placebo (n=1167) for 12 to 52 weeks and grouped based on percent change in LDL‐C from baseline to week 12 according to guideline‐established statin intensity categories. Factors associated with ≥30% reduction in LDL‐C were identified using logistic regression analyses. From baseline to week 12, BA lowered LDL‐C levels comparable to a moderate‐ or high‐intensity statin (≥30%) in 28.9% of patients; this degree of LDL‐C lowering was observed in 50.9% of patients not receiving background statin therapy. In a multivariable analysis, the absence of statins, female sex, a history of diabetes, ezetimibe use, and higher high‐sensitivity C‐reactive protein level were associated with increased rates of achieving ≥30% LDL‐C reduction with BA (P<0.01 for each). CONCLUSIONS: A large percentage of patients receiving BA achieved LDL‐C reductions comparable to a moderate‐ or high‐intensity statin. Factors including statin absence, female sex, diabetes history, ezetimibe use, and a higher high‐sensitivity C‐reactive protein level may be useful to identify patients who may have a greater LDL‐C reduction with BA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02666664, NCT02991118, NCT02988115, NCT03001076.