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Effects of bempedoic acid on CRP, IL-6, fibrinogen and lipoprotein(a) in patients with residual inflammatory risk: A secondary analysis of the CLEAR harmony trial

Published:February 13, 2023DOI:https://doi.org/10.1016/j.jacl.2023.02.002
Effects of bempedoic acid on CRP, IL-6, fibrinogen and lipoprotein(a) in patients with residual inflammatory risk: A secondary analysis of the CLEAR harmony trial
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      Highlights

      • •
        Bempedoic acid (BA) reduces hsCRP with minimal effect on fibrinogen, IL-6, or Lp(a).
      • •
        No correlation between lipid changes and hsCRP changes with BA.
      • •
        Findings for BA are almost identical to that of statin therapy.
      • •
        BA may be an option to treat residual inflammatory and residual cholesterol risk.

      Abstract

      While bempedoic acid (BA), an inhibitor of ATP citrate lyase, lowers high-sensitivity C-reactive protein (hsCRP) and low-density lipoprotein cholesterol (LDL-C), the mechanisms underlying the potential anti-inflammatory effects of BA are uncertain, as are effects of this agent on lipoprotein(a).  To address these issues, we conducted a secondary biomarker analysis of the randomized placebo-controlled multi-center CLEAR Harmony trial which included 817 patients with known atherosclerotic disease and/or heterozygous familial hypercholesterolemia who were taking maximally tolerated statin therapy and had residual inflammatory risk, defined as a baseline hsCRP ≥2 mg/L. Participants were randomly allocated in a 2:1 ratio to oral BA 180 mg once daily or matching placebo.  Placebo-corrected median percent changes (95% CI) from baseline to 12 weeks associated with BA were −21.1% (−23.7 to −18.5) for LDL-C; −14.3% (−16.8 to −11.9) for non–high-density lipoprotein cholesterol; −12.8% (−14.8 to −10.8) for total cholesterol; −8.3% (−10.1 to −6.6) for high-density lipoprotein cholesterol (HDL-C); −13.1% (−15.5 to −10.6) for apolipoprotein B; 8.0% (3.7 to 12.5) for triglycerides; −26.5% (−34.8 to −18.4) for hsCRP; 2.1% (−2.0 to 6.4) for fibrinogen, −3.7% (−11.5, 4.3) for interleukin-6; and 2.4% (0.0 to 4.8) for lipoprotein(a). There was no correlation between BA associated lipid changes and BA associated change in hsCRP (all r<0.05), except for a weak correlation with HDL-C (r = 0.12). Thus, the pattern of lipid lowering and inflammation inhibition with BA is almost identical to what is observed with statin therapy suggesting that BA could be a useful treatment option to address both residual cholesterol risk and residual inflammatory risk.

      TRIAL REGISTRATION

      ClinicalTrials.gov Identifier: NCT02666664; https://clinicaltrials.gov/ct2/show/NCT02666664.

      Keywords

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      Article info

      Publication history

      Published online: February 13, 2023
      Accepted: February 8, 2023
      Received: November 13, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Conflict of interest: Ridker: Dr. Ridker has received institutional research grant support from Novartis, Kowa, Amarin, Pfizer, Esperion, and the NHLBI; has served as a consultant to Novartis, Flame, Agepha, AstraZeneca, Janssen, Civi Biopharm, Glaxo Smith Kline, SOCAR, Novo Nordisk, Uptton, Omeicos, Health Outlook, Montai Health, New Amsterdam, Boehringer-Ingelheim, Angiowave, RTI; Zomagen, Cytokinetics, Horizon Therapeutics, and Cardio Therapeutics; and receives compensation for service on the Peter Munk Advisory Board (University of Toronto), the Leducq Foundation, Paris FR, and the Baim Institute (Boston, MA). Lei: Dr. Lei is an employee of Esperion Therapeutics. Ray: Dr. Ray has received institutional research grant(s)/support from Amgen, MSD, Pfizer, Regeneron, and Sanofi, and served as a consultant for or received honoraria from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Cargene, CRISPR, Eli Lilly, Esperion Therapeutics, Kowa, Medicines Company, MSD, New Amsterdam, Novo Nordisk, Novartis, Pfizer, Regeneron, Resverlogix, Sanofi, Scribe Therapeutics, Vaxxinity, Viatris and Zuellig Pharma. Ballantyne: Dr. Ballantyne has received research grants/support from Abbott Diagnostics, Akcea, Amarin, Amgen, Esperion Therapeutics, Ionis, Novartis, Regeneron, Roche Diagnostic, Sanofi-Synthelabo, National Institutes of Health, American Diabetes Association and the American Heart Association (all paid to the institution, not to the individual); has also served as a consultant for Abbott Diagnostics, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Esperion, Intercept, Ionis, Matinas BioPharma, Merck, Novartis, Novo Nordisk, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. Bradwin: None. Rifai: None.

      Author contributions: Concept and design: Ridker, Rifai; Acquisition, analysis, or interpretation of data: Ridker, Lei, Ray, Ballantyne, Bradwin, Rifai; Drafting of the manuscript: Ridker; Critical revision of the manuscript for important intellectual content: Ridker, Lei, Ray, Ballantyne, Bradwin, Rifai; Statistical analysis: Lei; Administrative, technical, or material support: Bradwin, Rifai; Supervision: None; Author access to data: Dr Ridker had access to all the study data and takes responsibility for the integrity of the data and the accuracy of the data analysis.

      Identification

      DOI: https://doi.org/10.1016/j.jacl.2023.02.002

      Copyright

      © 2023 National Lipid Association. Published by Elsevier Inc. All rights reserved.

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