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.

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.

• Authors: Paul M Ridker, Lei Lei, Kausik K Ray, Christie M Ballantyne, Gary Bradwin, Nader Rifai
• Journal: Journal of clinical lipidology (J Clin Lipidol) 2023 Mar-Apr Vol. 17 Issue 2 Pg. 297-302 ISSN: 1933-2874 [Print] United States
• PMID: 36813656 (Publication Type: Randomized Controlled Trial, Multicenter Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023. Published by Elsevier Inc.

Chemical References

• 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Cholesterol, LDL
• Interleukin-6
• C-Reactive Protein
• Fibrinogen
• Lipoprotein(a)
• Cholesterol

Topics

• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Cholesterol, LDL
• Interleukin-6
• C-Reactive Protein
• Fibrinogen
• Lipoprotein(a)
• Treatment Outcome
• Cholesterol
• Double-Blind Method