Lipid lowering with bempedoic acid added to a proprotein convertase subtilisin/kexin type 9 inhibitor therapy: A randomized, controlled trial
Open accessAbstract
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) lower low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. However, some patients receiving PCSK9i therapy might require additional lipid-lowering therapy (LLT) to reach LDL-C goals. Bempedoic acid is an oral, once-daily, ATP-citrate lyase inhibitor that significantly lowers LDL-C in patients with hypercholesterolemia when given alone or as add-on therapy to statins and/or ezetimibe. OBJECTIVE: Assess safety and efficacy of bempedoic acid added to PCSK9i (evolocumab) background therapy in patients with hypercholesterolemia. METHODS: This phase 2, randomized, double-blind, placebo-controlled study was conducted in three phases: 1.5-month screening/washout period including discontinuation of all LLTs, a 3-month period wherein patients initiated background PCSK9i therapy, and a 2-month treatment period in which patients were randomized 1:1 to receive bempedoic acid 180 mg or placebo once daily while continuing PCSK9i therapy. RESULTS: Of 59 patients randomized, 57 completed the study. Mean baseline LDL-C after 3 months of PCSK9i background therapy was 103.1 ± ± 30.4 mg/dL. Bempedoic acid added to background PCSK9i therapy significantly lowered LDL-C by 30.3% (P < .001) vs placebo. Compared with placebo, bempedoic acid significantly lowered apolipoprotein B, non-high-density lipoprotein cholesterol, and total cholesterol (nominal P < .001 for all), and high-sensitivity C-reactive protein (P = .029). When added to background PCSK9i therapy, the safety profile of bempedoic acid was comparable to that observed for placebo. CONCLUSIONS: When added to a background of PCSK9i therapy, bempedoic acid significantly lowered LDL-C levels with a safety profile comparable to placebo in patients with hypercholesterolemia.
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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 [13]
The cited paper reports a single randomized trial. Its Study design and treatment and Statistical analysis sections describe that trial, but the passages do not assess risk of bias across 11 trials. Searches for the seven-low/four-moderate breakdown and for risk-of-bias assessment found no supporting passage in our copy. (LLM, conf=0.75)
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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 ].”
- Authors
- Rubino, J., MacDougall, D. E., Sterling, L. R., Kelly, S. E., McKenney, J. M., & Lalwani, N. D.
- Affiliations
- PMG Research (US)
- Esperion Therapeutics (United States) (US)
- Virginia Commonwealth University (US)
- Corresponding author
- Rubino, John
- MacDougall, Diane E.
- Sterling, Lulu Ren
- Kelly, Stephanie E.
- McKenney, James M.
- Lalwani, Narendra D.
- Venue
- Journal of Clinical Lipidology
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 15
- Issue
- 4
- Pages
- 593-601
- ISSN
- 1876-4789 (ISSN-L)
- 1933-2874
- OpenAlex
- W2949390415
- Cited by
- 69
- References
- 6
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 17 · 2023: 20 · 2022: 7 · 2021: 4 · 2020: 3
- FWCI
- 11.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of clinical lipidology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Esperion Therapeutics
- 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, PCSK9 inhibitors, evolocumab, hypercholesterolemia, LDL cholesterol lowering, ATP-citrate lyase inhibitor, apolipoprotein B, non-HDL cholesterol, high-sensitivity C-reactive protein, drug safety
- MeSH terms
- Proprotein Convertase 9, PCSK9 Inhibitors, Aged, Hypolipidemic Agents, Dicarboxylic Acids, Double-Blind Method, Drug Therapy, Combination, Fatty Acids, Female, Humans, Hypercholesterolemia, Cholesterol, LDL, Male, Middle Aged
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