Brief Communication| Volume 17, ISSUE 2, P297-302, March 2023

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:


      • 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.


      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 Identifier: NCT02666664;


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