Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy

Eur J Prev Cardiol. 2020 Apr;27(6):593-603. doi: 10.1177/2047487319864671. Epub 2019 Jul 29.


Aims: The aim of this study was to evaluate the low-density lipoprotein cholesterol lowering efficacy and safety of a bempedoic acid 180 mg and ezetimibe 10 mg fixed-dose combination in patients with hypercholesterolemia and a high risk of cardiovascular disease receiving maximally tolerated statin therapy.

Methods: This phase 3, double-blind clinical trial enrolled adult patients at high risk of cardiovascular disease due to atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or multiple cardiovascular disease risk factors. Patients were randomly assigned (2:2:2:1) to treatment with the fixed-dose combination, bempedoic acid 180 mg, ezetimibe 10 mg or placebo added to stable background statin therapy for 12 weeks. The primary efficacy endpoint was the percentage change from baseline to week 12 in low-density lipoprotein cholesterol.

Results: Among the 301 patients included in the primary analysis, the mean baseline low-density lipoprotein cholesterol level was 3.87 mmol/L (149.8 mg/dL). At week 12, the fixed-dose combination lowered low-density lipoprotein cholesterol (-36.2%) significantly more than placebo (1.8% (placebo-corrected difference -38.0%); P < 0.001), ezetimibe alone (-23.2%; P < 0.001) or bempedoic acid alone (-17.2%; P < 0.001). The fixed-dose combination lowered low-density lipoprotein cholesterol levels similarly across subgroups, including patients receiving high-intensity, other-intensity or no statin therapy. Improvements with the fixed-dose combination were also observed in secondary efficacy endpoints, including high-sensitivity C-reactive protein. In this trial, fixed-dose combination treatment had a generally similar safety profile compared with bempedoic acid, ezetimibe or placebo.

Conclusion: The bempedoic acid and ezetimibe fixed-dose combination significantly lowered low-density lipoprotein cholesterol versus placebo or other oral monotherapies and had a favourable safety profile when added to maximally tolerated statin therapy in patients with hypercholesterolemia and high cardiovascular disease risk.

Trial registration: identifier: NCT03337308.

Keywords: Bempedoic acid; LDL-cholesterol; ezetimibe; hydroxymethylglutaryl-CoA reductase inhibitors; hypercholesterolemia; hyperlipidemias; hypolipidemic agents; lipid-regulating agents.

Publication types

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

MeSH terms

  • Aged
  • Anticholesteremic Agents / administration & dosage*
  • Anticholesteremic Agents / adverse effects
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / blood*
  • Dicarboxylic Acids / administration & dosage*
  • Dicarboxylic Acids / adverse effects
  • Double-Blind Method
  • Down-Regulation
  • Drug Combinations
  • Ezetimibe / administration & dosage*
  • Ezetimibe / adverse effects
  • Fatty Acids / administration & dosage*
  • Fatty Acids / adverse effects
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / diagnosis
  • Hypercholesterolemia / drug therapy*
  • Male
  • Middle Aged
  • Time Factors
  • Treatment Outcome
  • United States


  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol, LDL
  • Dicarboxylic Acids
  • Drug Combinations
  • Fatty Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  • Ezetimibe

Associated data