Efficacy and safety of bempedoic acid in women with hypercholesterolemia: Pooled analyses from phase 3 trials

Background and aims Sex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid. Methods Patients were grouped into two pools: atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) “on statins”, and “low-dose or no statin”. Percent changes from baseline to at least week 12 in low-density lipoprotein-cholesterol (LDL-C), non–high-density lipoprotein-cholesterol (non–HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed by statin pool and sex. Results Overall, 3623 patients were included (bempedoic acid, 2425; placebo, 1198). Significant reductions in lipid parameters and hsCRP were observed with bempedoic acid vs . placebo in both sexes in the ASCVD and/or HeFH on statins (n = 3009) and the low-dose or no statin (n = 614) pools ( p ≤0.002). Compared with men, women had significantly greater placebo-corrected reductions in LDL-C (−21.2% vs . −17.4%; p =0.044), non–HDL-C (−17.3% vs . −12.1%; p =0.003), TC (−13.8% vs . −10.5%; p =0.012), and Apo B ( − 16.0% vs . −11.3%; p =0.004) in the ASCVD and/or HeFH on statins pool. Women had numerically greater reductions than men in lipid parameters in the low-dose or no statin pool and hsCRP in both pools. The safety of bempedoic acid was comparable between sexes. Conclusions In this pooled analysis, women experienced significant improvements in levels of LDL-C and other lipid parameters with bempedoic acid. ### Competing Interest Statement A.C.G. has received research grants/support from Amgen, Akcea/Ionis, Arrowhead, Esperion Therapeutics, Inc., NewAmsterdam Pharma, Novartis, Pfizer, Regeneron, and Sanofi; has served as a consultant for Akcea, Esperion Therapeutics, Inc., NewAmsterdam Pharma, IONIS, Novartis, and Regeneron, and performed editorial work for the Merck Manuals. M.B. has received research grants/support from Amgen, Sanofi, Mylan/Viatris, and Valeant, and has served as a consultant for Amgen, Daiichi Sankyo, Esperion Therapeutics, Inc., Freia Pharmaceutici, Herbapol, Kogen, KRKA, Novartis, Novo Nordisk, Polfarmex, Polpharma, Regeneron, Sanofi Aventis, Servier, Teva, and Zentiva; he serves as Chief Medical Officer at Nomi Biotech Corporation Ltd. A.L.C. has received research grants/support from Amarin, Amgen, Menarini, Mylan, Sanofi, and Sanofi Regeneron, and has served as a consultant for or received honoraria from Akcea, Amarin, Amgen, Daiichi Sankyo, Esperion Therapeutics, Inc., Ionis, Kowa, Medco, Menarini, MSD, Mylan, Novartis, Recordati, Regeneron, Sanofi, and The Corpus. P.B.D. has received institutional research grants/support from Regeneron, Regenxbio, and Retrophin/Travere, and has served as a consultant for Akcea, Esperion Therapeutics, Inc., Ionis, Kaneka, Regeneron, and Novo Nordisk. L.A.L. has received research grants/support from Amgen, AstraZeneca, Kowa, The Medicines Company, and Novartis. He has also served as an advisor and/or provided continuing medical education on behalf of Amarin, Amgen, AstraZeneca, Esperion Therapeutics, Inc., HLS, Merck, Novartis, Pfizer, and Sanofi. J.C.H. is an employee of Esperion Therapeutics, Inc. and may own Esperion stock or stock options. L.L. is a consultant contracted by Esperion Therapeutics, Inc. and may own Esperion stock or stock options. G.B.J.M. has received research grant(s)/support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, HLS Therapeutics, Merck, Novo Nordisk, and Sanofi, and has served as a consultant for these companies, as well as Esperion Therapeutics, Inc., Novartis, Amgen, Sanofi, and Servier. ### Funding Statement This work was supported by Esperion Therapeutics, Inc. The work of ALC was supported in part by Ministero della Salute, Ricerca corrente. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: In all four trials (CLEAR Wisdom [[NCT02991118][1]], CLEAR Harmony [[NCT02666664][2]], CLEAR Tranquility [[NCT03001076][3]], and CLEAR Serenity [[NCT02988115][4]]) protocols were approved by local independent ethics committees at each study site, and all study participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. 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