USA: Bempedoic Acid Study Findings

A recent study published in the Journal of Clinical Lipidology has shown that bempedoic acid (BA), an ATP citrate lyase inhibitor, may potentially reduce inflammation and lower cholesterol in patients with known atherosclerotic disease and/or heterozygous familial hypercholesterolemia.

Study Overview

Bempedoic acid (BA) has been shown to inhibit ATP citrate lyase and effectively reduce both LDL-C and high-sensitivity C-reactive protein (hs-CRP). However, the underlying mechanisms that could lead to anti-inflammatory effects with BA are unknown, as is its potential impact on lipoprotein.

The study was a secondary biomarker analysis, randomized placebo-controlled multi-centre trial called the CLEAR Harmony trial. The trial included 817 patients with atherosclerotic disease or heterozygous familial hypercholesterolemia who were already taking statin therapy. Participants were randomly allocated in a 2:1 ratio to receive oral BA (180mg o.d.) or a placebo over a 12-week period.

Key Clinical Findings

• The results showed that BA was associated with significant reductions in:
  • Low-density lipoprotein cholesterol (-21.1%)
  • Non-high-density lipoprotein cholesterol (-14.3%)
  • Total cholesterol (-12.8%)
  • Apolipoprotein B (-13.15%)
  • High-density lipoprotein-cholesterol (-8.3%)
  • High-sensitivity C-reactive protein (-26.5%) over 12 weeks
• There was a slight increase in lipoprotein(a) (2.4%) and fibrinogen (2.1%) and minimal effect on Interleukin-6 (-3.7%).
• There was no significant correlation between BA-associated changes in lipid markers and hs-CRP, except for a weak correlation with HDL-C.
• The study also found that the lipid-lowering and inflammation inhibition pattern with BA was almost identical to what is observed with statin therapy.

The study results suggest that BA may be a useful treatment option to address both residual cholesterol and inflammatory risks in patients already taking statins. The exact mechanisms underlying the potential anti-inflammatory effects of BA are still uncertain, and further research is needed to fully understand the drug's effects on lipoprotein(a).

Dr. Paul Ridker, the study's lead author, noted that "these findings suggest that BA has the potential to be a very important addition to the armamentarium of lipid-lowering therapies. However, he also cautioned that more research is needed to determine the long-term effects of BA and its potential side effects.”

Reference

Ridker P., Lei L., Ray K., Ballantyne C., Bradwin G., Rifai N., 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 Journal of Clinical Lipidology, 2023, 02.13 DOI: https://doi.org/10.1016/j.jacl.2023.02.002