†Efficacy and Safety of Bempedoic Acid in Patients with Metabolic Syndrome

Abstract

<h3>Lead Author's Financial Disclosures</h3> MDS has received funding/grant support from Amgen, the National Institutes of Health, and Novartis, and honorarium for consultancy from Amgen, Novartis, Novo Nordisk and Regeneron. <h3>Study Funding</h3> Esperion Therapeutics, Inc. <h3>Background/Synopsis</h3> Metabolic syndrome (MetS) is associated with increased risk of cardiovascular events. Bempedoic acid (BA) is an ATP citrate lyase inhibitor that lowers LDL-C in patients with hypercholesterolemia. <h3>Objective/Purpose</h3> To assess efficacy and safety of BA in patients with and without metabolic syndrome. <h3>Methods</h3> We investigated the lipid-lowering efficacy, safety, and effect of BA on glycemic parameters and high-sensitivity C-reactive protein (hsCRP) according to baseline metabolic status using pooled data (n=3623) from 4 phase-3, randomized, double-blind studies in which patients were randomized 2:1 to BA or placebo (PBO) for 12-52 weeks. Patients with diabetes mellitus (n=1114) were excluded from the analyses. The remaining patients were categorized as having MetS (n=936; defined using modified IAS guidelines with BMI as a proxy for waist circumference) or nonMetS (n=1573). Assessments included absolute or % change from baseline to week 12 in LDL-C, other lipid parameters, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and hsCRP; and treatment-emergent adverse events (TEAEs). <h3>Results</h3> Background statin intensity was similar between groups (Table). BA significantly lowered LDL C at week 12 vs PBO, to a greater extent in patients with MetS than nonMetS (PBO corrected % change from baseline of −22.3 MetS; −18.4 nonMetS; interaction P=.0472). BA also significantly lowered total cholesterol, non-HDL-C, and apo B % change at week 12 vs PBO to a similar extent in both subgroups. In patients with MetS, absolute reductions in HbA1c and FPG were significantly greater with BA vs PBO; changes in HbA1C and FPG were not significantly different for BA vs PBO in the nonMetS group (interaction P=.0003 and .0017, respectively). hsCRP % change from baseline was substantially lowered with BA vs PBO in both groups (insignificant interaction based on log of hsCRP absolute change). The incidence of TEAEs was comparable in both subgroups.subgroups and greater lowering of LDL-C, HbA1c, and FPG levels in patients with MetS vs nonMetS. <h3>Conclusions</h3> Overall, BA demonstrated comparable safety in both metabolic subgroups and greater lowering of LDL-C, HbA1c, and FPG levels in patients with MetS vs nonMetS.