Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy
Open accessAbstract
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: ClinicalTrials.gov identifier: NCT03337308.
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Overall risk of bias was low in 7 of 11 included trials and moderate in 4 trials.
“The overall risk of bias was low 7 of 11 trials [7, 9–12, 15, 16], with 4 trials being assessed as having a moderate risk of bias [8, 13, 14, 17].”
From The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials (2024) · cites this paper as [16]
The Methods (Statistical analysis) and Discussion describe this individual trial and its data-integrity concerns, but do not assess the risk of bias across 11 trials. Searches for the low/moderate risk-of-bias counts found no passage in our copy reporting them. (LLM, conf=0.76)
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Cites
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“The overall risk of bias was low 7 of 11 trials [7, 9–12, 15, 16], with 4 trials being assessed as having a moderate risk of bias [8, 13, 14, 17 ].”
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Self-citation
- Authors
- Ballantyne, C. M., Laufs, U., Ray, K. K., Leiter, L. A., Bays, H. E., Goldberg, A. C., Stroes, E. S., MacDougall, D., Zhao, X., & Catapano, A. L.
- Affiliations
- Baylor College of Medicine (US)
- University Hospital Leipzig (DE)
- Imperial College London (GB)
- St. Michael's Hospital (CA)
- Louisville Metabolic and Atherosclerosis Research Center (US)
- Washington University School of Medicine, USA
- Amsterdam UMC Location University of Amsterdam (NL)
- Esperion Therapeutics (United States) (US)
- University of Milan (IT)
- Corresponding author
- Ballantyne, Christie M
- ORCID
- Venue
- European Journal of Preventive Cardiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-07-29
- Volume
- 27
- Issue
- 6
- Pages
- 593-603
- ISSN
- 2047-4873 (ISSN-L)
- 2047-4881
- PMC
- PMC7153222
- OpenAlex
- W2965327853
- Cited by
- 358
- References
- 8
- Citations by year
- 2026: 30 · 2025: 44 · 2024: 57 · 2023: 51 · 2022: 65 · 2021: 60 · 2020: 48 · 2019: 2
- FWCI
- 41.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Journal of Preventive Cardiology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Qucosa (Saxon State and University Library Dresden) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- American Heart Association
- Amgen
- Eli Lilly and Company
- Pfizer
- Sanofi
- Regeneron Pharmaceuticals
- Ionis Pharmaceuticals
- Amarin Corporation
- Medicines Company
- Kowa Company
- Mylan
- European Atherosclerosis Society
- National Institute for Health and Care Research
- Esperion Therapeutics
- National Institutes of Health
- Abbott Diagnostics
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- bempedoic acid, ezetimibe, fixed-dose combination, hypercholesterolemia, LDL cholesterol lowering, high cardiovascular risk, atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, high-sensitivity C-reactive protein, statin intolerance, drug safety, lipid-lowering therapy
- MeSH terms
- Ezetimibe, Aged, Anticholesteremic Agents, Cardiovascular Diseases, Dicarboxylic Acids, Double-Blind Method, Drug Combinations, Fatty Acids, Female, Humans, Hypercholesterolemia, Cholesterol, LDL, Male, Middle Aged, Time Factors, United States, Biomarkers, Down-Regulation, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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