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

J Am Heart Assoc. 2022 Aug 2;11(15):e024531. doi: 10.1161/JAHA.121.024531. Epub 2022 Aug 2.


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.

Keywords: atherosclerotic cardiovascular disease; statin intolerance.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents* / therapeutic use
  • C-Reactive Protein
  • Cholesterol
  • Cholesterol, LDL
  • Dicarboxylic Acids
  • Drug Therapy, Combination
  • Ezetimibe / therapeutic use
  • Fatty Acids
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Treatment Outcome


  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Dicarboxylic Acids
  • Fatty Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  • C-Reactive Protein
  • Cholesterol
  • Ezetimibe

Associated data

  • ClinicalTrials.gov/NCT02666664
  • ClinicalTrials.gov/NCT02988115
  • ClinicalTrials.gov/NCT03001076
  • ClinicalTrials.gov/NCT02991118