Combination of bempedoic acid, ezetimibe, and atorvastatin in patients with hypercholesterolemia: A randomized clinical trial

Atherosclerosis. 2021 Mar:320:122-128. doi: 10.1016/j.atherosclerosis.2020.12.023. Epub 2020 Dec 31.


Background and aims: Many patients with hypercholesterolemia fail to achieve sufficient low-density lipoprotein cholesterol (LDL-C) lowering despite use of guideline-recommended lipid-lowering therapies. This study evaluated LDL-C lowering with the combination of bempedoic acid, ezetimibe, and atorvastatin.

Methods: This was a phase 2, randomized, double-blind, placebo-controlled study (NCT03051100). After washout of lipid-lowering drugs, patients were randomized 2:1 to triple therapy (bempedoic acid 180 mg, ezetimibe 10 mg, and atorvastatin 20 mg; n = 43) or placebo (n = 20) once daily for 6 weeks. The primary endpoint was percent change from baseline in LDL-C at week 6.

Results: Mean age for the 63 randomized patients was 61.2 years; baseline LDL-C was 154.8 mg/dL. At week 6, mean LDL-C lowering with triple therapy (-63.6%) was significantly greater than with placebo [-3.1%; difference, -60.5% [(95% CI, -68.0% to -53.0%); p < 0.001]. Significant reductions with triple therapy vs. placebo were also observed for non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein (p < 0.001 for all). With triple-therapy, 90% of patients achieved LDL-C <70 mg/dL and 95% of patients had ≥50% lower LDL-C from baseline to week 6; no patients in the placebo group met either goal. The majority of treatment-emergent adverse events were mild to moderate in severity. No patients experienced clinically relevant elevations in aminotransferase or creatine kinase levels.

Conclusions: Among patients with hypercholesterolemia, the combination of bempedoic acid, ezetimibe, and atorvastatin significantly lowered LDL-C, allowing more than 90% of patients in this study to reach guideline-recommended LDL-C goals.

Keywords: Bempedoic acid; Ezetimibe; Hypercholesterolemia; Lipid-lowering therapy; Low-density lipoprotein cholesterol; Statin.

Publication types

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

MeSH terms

  • Anticholesteremic Agents* / adverse effects
  • Atorvastatin / adverse effects
  • Dicarboxylic Acids
  • Double-Blind Method
  • Drug Therapy, Combination
  • Ezetimibe / adverse effects
  • Fatty Acids
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects
  • Hypercholesterolemia* / diagnosis
  • Hypercholesterolemia* / drug therapy
  • Middle Aged
  • Treatment Outcome


  • Anticholesteremic Agents
  • Dicarboxylic Acids
  • Fatty Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  • Atorvastatin
  • Ezetimibe