Physicians' Academy for Cardiovascular Education

Bempedoic acid associated with reduced MACE and mortality in primary prevention

Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients

Literature - Nissen SE, Menon V, Nicholls SJ, et al. - JAMA. 2023 Jun 24 [Online ahead of print]. doi: 10.1001/jama.2023.9696

Introduction and methods


The recently published CLEAR Outcomes (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) trial showed treatment with bempedoic acid reduced the risk of MACE in statin-intolerant patients compared with placebo [1]. In this mixed population of primary and secondary prevention patients, a considerable proportion exhibited characteristics associated with a high CVD risk but with no a prior CV event.

Aim of the study

In a prespecified subgroup analysis of the CLEAR Outcomes trial, the authors examined the effects of bempedoic acid on the occurrence of MACE in primary prevention.


The CLEAR Outcomes trial was an international, double-blind, placebo-controlled, phase 3 RCT in which 13,970 statin-intolerant patients with (current or previous) high CVD risk were enrolled, of whom 4206 (30%) were in the primary prevention group. Participants were randomized to oral bempedoic acid 180 mg once daily or matching placebo. Median follow-up time for the primary prevention group was 39.9 months.


The primary efficacy endpoint was time to the first occurrence of a composite outcome of CV death, nonfatal MI, nonfatal stroke, or coronary revascularization (4-component MACE). Key secondary endpoints included: (1) time to first occurrence of a composite outcome of CV death, nonfatal stroke, or nonfatal MI (3-component MACE); (2) fatal or nonfatal MI; (3) coronary revascularization; (4) fatal or nonfatal stroke; (5) CV death; and(6) all-cause mortality.

Main results




In a secondary subgroup analysis of the CLEAR Outcomes trial comprising 4206 statin-intolerant patients with high CVD risk but no prior CV event, bempedoic acid treatment was associated with a risk reduction of MACE, CV death, and all-cause mortality compared with placebo. “These findings emphasize the potential value of lipid-modulating therapy in patients who have had no prior cardiovascular event but who have a high risk for a first event, a population that is currently undertreated,” according to the authors.


Show references

Find this article online at JAMA.

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