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

Background

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.

Methods

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

Conclusion

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.

References

Show references

Find this article online at J Clin Lipidol.

Share this page with your colleagues and friends: