†Safety and Efficacy of Bempedoic Acid in Patients with Renal Impairment

Abstract

<h3>Lead Author's Financial Disclosures</h3> PPT has received honorarium for consultancy from Amarin, AstraZeneca, Kowa, Merck, Novo-Nordisk, and Resverlogix. <h3>Study Funding</h3> Esperion Therapeutics, Inc. <h3>Background/Synopsis</h3> Patients with renal impairment and elevated levels of low-density lipoprotein cholesterol (LDL-C) are at very high risk for cardiovascular disease. Statins are safe and effective in this population but are often underutilized and underdosed; additional non-statin therapies to lower LDL-C are needed. Bempedoic acid (BA) is an ATP citrate lyase inhibitor that lowers LDL-C. <h3>Objective/Purpose</h3> To evaluate the safety and efficacy of BA in patients with Stage 2 or Stage 3a+b renal impairment. <h3>Methods</h3> Data were pooled from four phase 3 studies in which patients were randomized 2:1 to BA or placebo (PBO) for 12 to 52 weeks. All studies permitted stable background lipid-lowering therapy: in 2 studies, patients received background moderate- to high-intensity statin, and in 2 studies, patients had a history of statin intolerance and received low-dose or no statin. Patients were grouped by baseline estimated glomerular filtration rate (eGFR [mL/min/1.73m2]) into the following renal function subgroups: Stage 1 (≥90), Stage 2 (60-89) or Stage 3a+b (30-59). <h3>Results</h3> A total of 3,619 (2,422 BA; 1,197 PBO) patients were included in the analysis. Baseline Stage 2 or Stage 3a+b renal impairment was present in 63% and 15% of patients in each treatment arm, respectively; 22% of the patients had Stage 1 renal function at baseline. LDL-C lowering of BA was similar across renal function subgroups with significant reductions at week 12 from baseline in each subgroup: Stage 1-20.8%, Stage 2 -18.8% and Stage 3a+b -21.1% (P < .0001 vs PBO for each; interaction P = .4442). Significant reductions in ApoB levels were also observed with BA treatment compared with PBO regardless of renal function (P < .0001). The overall pattern of adverse events was consistent across the renal function subgroups; any differences appeared to be driven by overall BA vs PBO differences rather than by renal function at baseline. Creatinine levels were generally consistent within each renal function subgroup in both arms with arm means varying by < 7% at each assessed time point through 52 weeks. <h3>Conclusions</h3> BA was generally well-tolerated among patients with Stage 2 or Stage 3a+b renal impairment and significantly lowered LDL-C regardless of renal function status.