Abstract Body (Do not enter title and authors here): Background: Bempedoic acid lowers LDL-cholesterol (LDL-C) and reduces major adverse cardiovascular events (MACE) in statin-intolerant patients at high risk for, or with, established cardiovascular (CV) disease. In the CLEAR Outcomes trial 41% of participants were taking other background lipid lowering therapies (LLT). It is unknown if bempedoic acid monotherapy reduces the risk for MACE and if the LDL-C lowering effect remains beyond 12 weeks.
Research Questions: Does bempedoic acid monotherapy decrease MACE compared with placebo? What is the LDL-C lowering effect of bempedoic acid monotherapy at 6 months?
Methods: CLEAR Outcomes randomized 13970 statin-intolerant adults at high risk for, or with established CV disease to bempedoic acid 180 mg or placebo. Fifty-nine percent of participants (8217) were not taking any LLT at baseline. In this subpopulation, we assessed the impact of bempedoic acid on the primary composite outcome of nonfatal myocardial infarction (MI), coronary revascularization, nonfatal stroke, CV death (MACE4) and key secondary outcomes including the composite of nonfatal MI, nonfatal stroke, CV death (MACE3), the individual components of MACE4, and all-cause death in a time-to-event manner using cox proportional hazards. Additionally, we assessed LDL-C change after 6 months of therapy.
Results: Compared with placebo, bempedoic acid monotherapy reduced MACE4 by 14% (HR 0.86; 95% CI, 0.76 – 0.97). Other key secondary outcomes demonstrated similar efficacy of bempedoic acid monotherapy compared with the overall trial population (Figure). Bempedoic acid monotherapy lowered LDL-C by -20.6% (95% CI, -21.7 to -19.6%) compared with placebo at 6 months. Serious adverse events (AE) were reported in 27.9% and 27.1% of patients who received bempedoic acid monotherapy and placebo, respectively. AEs that led to study drug discontinuation occurred in 11.3% and 11.0% of patients, respectively.
Conclusions: Bempedoic acid demonstrates similar efficacy and safety when taken as monotherapy compared with all participants in CLEAR Outcomes. These data support its use as monotherapy to reduce CV events in statin-intolerant patients with high CV risk.