Bempedoic Acid Significantly Reduces Total Cardiovascular Events, Study Finds

In a groundbreaking development, the Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial has unveiled a novel approach to tackling cardiovascular risk in patients intolerant to statins. The study focused on bempedoic acid, an ATP citrate lyase (ACL) inhibitor, which not only effectively lowered low-density lipoprotein cholesterol (LDL-C) but also demonstrated a significant reduction in the total incidence of major adverse cardiovascular events (MACE).

The study results were published in the journal JAMA Cardiology.

Bempedoic acid, an inhibitor of ATP citrate lyase (ACL), has been shown to decrease low-density lipoprotein cholesterol (LDL-C) levels and major adverse cardiovascular events (MACE) by 13% in patients facing high cardiovascular risk and exhibiting intolerance to statins and high-intensity statin medications. Despite these positive outcomes, the impact of bempedoic acid on the overall occurrence of cardiovascular events remains uncertain. Hence researchers conducted a CLEAR Outcomes trial to determine the impact of bempedoic acid on the total incidence of MACE.

Conducted between December 2016 and November 2022, the trial involved 13,970 patients, aged 65 on average, with 51.8% being male. These patients, at high risk for cardiovascular disease and unable to tolerate recommended statins, were randomly assigned to receive daily doses of bempedoic acid or a placebo.

The primary focus of the study was to assess the impact of bempedoic acid on the total occurrence of MACE, encompassing cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and coronary revascularization (MACE-4). The secondary focus of interest was the duration until the occurrence of the initial event related to cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (MACE-3).

Findings:

• Over a median follow-up period of 3.4 years, patients treated with bempedoic acid experienced a 21% reduction in LDL-C levels and a 22% reduction in high-sensitivity C-reactive protein (hsCRP) levels after 6 months. These outcomes alone underscore the efficacy of bempedoic acid in managing key risk factors for cardiovascular events.
• The study's pivotal finding lies in the association between bempedoic acid treatment and a substantial reduction in the risk of MACE-4 (hazard ratio [HR], 0.80), MACE-3 (HR, 0.83), myocardial infarction (HR, 0.69), and coronary revascularization (HR, 0.78).
•  While no statistically significant difference was observed for stroke (HR, 0.80), the overall impact on cardiovascular events is undeniable.

This breakthrough marks a significant advancement in cardiovascular treatment, particularly for individuals facing challenges with traditional statin therapies. Bempedoic acid not only addresses LDL-C levels but also demonstrates a tangible benefit in lowering the total number of cardiovascular events. This could potentially reshape treatment strategies for patients at high cardiovascular risk who have, until now, struggled with statin intolerance.

The findings open avenues for a new era in cardiovascular care, providing hope for improved outcomes and reduced risks for a population that has long grappled with limited therapeutic options. As research continues to unravel the potential of bempedoic acid, its role in cardiovascular disease management is poised to become increasingly pivotal.

Further reading: Nicholls SJ, Nelson AJ, Lincoff AM, et al. Impact of Bempedoic Acid on Total Cardiovascular Events: A Prespecified Analysis of the CLEAR Outcomes Randomized Clinical Trial. JAMA Cardiol. Published online January 17, 2024. doi:10.1001/jamacardio.2023.5155