Physicians' Academy for Cardiovascular Education

Bempedoic acid reduces hs-CRP, but not fibrinogen and IL-6 in patients with residual inflammatory risk

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

Literature - Ridker PM, Lei L, Ray KK, et al. - J Clin Lipidol. 2023 Feb 14;S1933-2874(23)00032-6. doi: 10.1016/j.jacl.2023.02.002

Introduction and methods


As bempedoic acid, an oral inhibitor of ATP citrate lyase, reduces LDL-c and also hs-CRP [1-6], it is a potential therapeutic option for patients with residual cholesterol or inflammatory risk. However, the mechanisms underlying its possible anti-inflammatory effects are uncertain.

Aim of the study

The authors examined the impact of bempedoic acid on fibrinogen and IL-6 and the relationships between bempedoic acid–associated changes in biomarkers (including lipids and lipoproteins) in patients with ASCVD and/or heterozygous familial hypercholesterolemia (HeFH) who were receiving maximal tolerated statin therapy and had residual inflammatory risk.


This was a secondary biomarker analysis of the multicenter, randomized, placebo-controlled CLEAR (Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen) Harmony trial. In this analysis, 817 patients with ASCVD and/or HeFH on maximally tolerated statin therapy who had residual inflammatory risk (defined as baseline hs-CRP ≥2 mg/L) were included who had been randomized (2:1 ratio) to bempedoic acid 180 mg once daily or matching placebo.

Change from baseline to 12 weeks in plasma levels of LDL-c, non–HDL-c, total cholesterol (TC), HDL-c, apoB, triglycerides, hs-CRP, fibrinogen, IL-6, and Lp(a) was measured.

Main results


In this secondary biomarker analysis of the CLEAR Harmony trial, bempedoic acid reduced levels of LDL-c and hs-CRP compared with placebo in patients with ASCVD and/or HeFH and residual inflammatory risk but had no effect on the inflammatory markers fibrinogen and IL-6. In addition, the bempedoic acid–associated reduction in hs-CRP did not correlate with the LDL-c reduction observed in the bempedoic acid group.

According to the authors, their “study, taken together with earlier work, suggest that bempedoic acid—acting upstream of statins—likely has LDL-lowering and anti-inflammatory effects through a similar hepatic mechanism.” They therefore believe that bempedoic acid may be useful to treat patients with residual inflammatory risk or residual cholesterol risk.


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Find this article online at J Clin Lipidol.

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