Comparative Cardiovascular Benefits of Bempedoic Acid and Statin Drugs.

Background: In the CLEAR (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) Outcomes trial, treatment of statin-intolerant patients with bempedoic acid produced a 21% decrease in low-density lipoprotein cholesterol (LDL-C) relative to placebo and a 13% relative reduction in the risk of major adverse cardiovascular events.
Objectives: This study sought to determine whether the relationship between LDL-C lowering and cardiovascular benefit achieved with bempedoic acid resembles that observed with statins when standardized per unit change in LDL-C.
Methods: To compare the treatment effect of bempedoic acid with statins, the methodology of the Cholesterol Treatment Trialists' Collaboration (CTTC) was applied to outcomes among the 13,970 patients enrolled in the CLEAR Outcomes trial. The CTTC endpoint of "major vascular event" was a composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal stroke, or coronary revascularization. HRs for CTTC-defined endpoints were normalized to 1 mmol/L differences in LDL-C levels between bempedoic acid and placebo groups.
Results: A first major vascular event occurred in 703 (10.1%) patients in the bempedoic acid group and 816 (11.7%) patients in the placebo group (HR: 0.85; 95% CI: 0.77-0.94). When normalized per 1 mmol/L reduction in LDL-C, the HR was 0.75 (95% CI: 0.63-0.90), comparable to the rate ratio of 0.78 reported for statins in the CTTC meta-analysis. Normalized risk reductions were similar for bempedoic acid and statins for the endpoints of major coronary events, nonfatal myocardial infarction, and coronary revascularization.
Conclusions: Cardiovascular risk reduction with bempedoic acid is similar to that achieved with statins for a given absolute magnitude of LDL-C lowering. (Evaluation of Major Adverse Cardiovascular Events in Participants With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated with Bempedoic Acid [ETC-1002] or Placebo [CLEAR Outcomes]; NCT02993406).
Competing Interests: Funding Support and Author Disclosures This work was funded by Esperion Therapeutics, Inc. The trial was designed by the sponsor, Esperion Therapeutics, in collaboration with the Cleveland Clinic Coordinating Center for Clinical Research (C5Research) and an academic Executive Committee. At the completion of the trial, the database was transferred to C5Research. Statisticians at Esperion conducted data analyses for this paper. Dr Lincoff wrote the first draft and all subsequent drafts of the paper, which was reviewed and approved by all authors. The sponsor reviewed the paper and provided suggested revisions, but the final decision on content was reserved for the academic authors. Dr Lincoff has received research funding for this trial from Esperion; has received grants from Eli Lilly, AbbVie, CSL, AstraZeneca, and Novartis; has received personal fees from Novo Nordisk, Eli Lilly, Akebia, Alnylam, Amgen, Ardelyx, Becton-Dickson, Brainstorm Cell, Cadrenal, Endologix, Fibrogen, GlaxoSmithKline, Intarcia, Medtronic, Neovasc, Provention Bio, and ReCor; and has received travel support for attending steering committee meetings from Novo Nordisk, Esperion, and Eli Lilly. Dr Ray has received unrestricted research grants (in the last 3 years) to Imperial College London from Amgen, Sanofi, Regeneron, Daiichi-Sankyo, and Ultragenix; has received consulting fees for serving as a member of the steering committee and executive committee of clinical trials and roles as principal investigator and national lead investigator from Novartis, Daiichi-Sankyo, Kowa, Esperion, Novo Nordisk, MSD, Lilly, Silence Therapeutics, AstraZeneca, New Amsterdam Pharma, Bayer, Beren Therapeutics, Cleerly, EmendoBio, Scribe, CRISPR, Vaxxinity, Amarin, Regeneron, Ultragenix, Cargene, and Resverlogix; has served on advisory boards, providing advice on data, its interpretation, and future lines of research; has received lecture fees for Continuing Medical Education and non–Continuing Medical Education symposia at international meetings from Novartis, Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Viatris, Amarin, Biologix Pharma, Sanofi, Amgen, Esperion, Daiichi-Sankyo, and Macleod Pharma; owns stock options in New Amsterdam Pharma and PEMI31; and has served as European Atherosclerosis Society President (unpaid). Dr Sasiela was an employee of, has served as a paid consultant for, and owns stock in Esperion Therapeutics, Inc. Dr Nicholls has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, Novartis, InfraReDx, and Sanofi-Regeneron; and has served as a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi-Regeneron, Novo Nordisk, CSL Sequiris, and Vaxxinity. Dr Li is an employee of Esperion Therapeutics, Inc. Dr Cho has served on the steering committee for the CLEAR Outcomes trial. Dr Libby has served as an unpaid consultant for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Novo Nordisk, Novartis, Pfizer, Sanofi-Regeneron, Cartesian, Esperion, Genentech, and Moderna; has served as an unpaid scientific advisory board member for the Baim Institute, Medimmune, Dewpoint, Pfizer, DalCor Pharmaceuticals, Olatec Therapeutics, XBiotech Inc, Caristo, CSL Behring, PlaqueTech, TenSixteen Bio, Soley Therapeutics, and Elucid Bioimaging; has received laboratory funding from Pfizer and CSL Behring; holds patents pending for use of canakinumab and for treatment for brain ischemia-reperfusion injury; has served as an unpaid consultant or been involved in clinical trials for Amgen, AstraZeneca, the Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Moderna, Novo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; has served on the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Eulicid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, PlaqueTec, TenSixteen Bio, Soley Therapeutics, and XBiotech Inc; has received research funding to his laboratory in the last 2 years from Novartis, Novo Nordisk, and Genentech; has served on the board of directors for XBiotech Inc; has held a financial interest in Xbiotech (a company developing therapeutic human antibodies), TenSixteen Bio (a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential to discover and develop novel therapeutics to treat age-related diseases), and Soley Therapeutics (a biotechnology company combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics); and has had his interests reviewed and managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies. Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd., Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, Valeo Pharma; and has received salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Failure Society, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and TIMI Study Group (Brigham Health). Dr Nissen has received grant support from Esperion for the CLEAR Outcomes Trial; and the Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from AbbVie, AstraZeneca, Arrowhead, Amgen, Bristol Myers Squibb, Eli Lilly, Medtronic, MyoKardia, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics, in which Dr Nissen is involved in these clinical trials but receives no personal remuneration for his participation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)