Rationale and design of the effect of evolocumab in patients at high cardiovascular risk without prior myocardial infarction or stroke (VESALIUS-CV) trial.

Autor: Bohula EA; TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address: ebohula@bwh.harvard.edu., Marston NA; TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Ruzza A; Amgen, Thousand Oaks, CA., Murphy SA; TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., De Ferrari GM; Department of Medical Sciences, University of Turin and Department of Cardiology, Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Turin, Italy., Diaz R; Estudios Clínicos Latino America, Santa Fe, Argentina., Leiter LA; Li Ka Shing Knowledge Institute of St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada., Elliott-Davey M; Amgen, Cambridge, United Kingdom., Wang H; Amgen, Thousand Oaks, CA., Bhatia AK; Amgen, Thousand Oaks, CA., Giugliano RP; TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Sabatine MS; TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Jazyk: angličtina
Zdroj: American heart journal [Am Heart J] 2024 Mar; Vol. 269, pp. 179-190. Date of Electronic Publication: 2023 Dec 29.
DOI: 10.1016/j.ahj.2023.12.004
Abstrakt: Background: The reduction of low-density lipoprotein cholesterol (LDL-C) with evolocumab, a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9i), reduces the risk of major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD) with a prior MI, prior stroke, or symptomatic peripheral artery disease, with no offsetting safety concerns. The effect of evolocumab on CV outcomes in lower risk patients without a history of MI or stroke has not been explored.
Study Design: VESALIUS-CV is a randomized, double-blind, placebo-controlled, global clinical trial designed to evaluate the effect of evolocumab on the risk of major cardiovascular events in patients at high cardiovascular risk but without a prior ischemic event. The study population consists of 12,301 patients with atherosclerosis or high-risk diabetes mellitus without a prior MI or stroke; an LDL-C ≥ 90 mg/dL, or non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 120 mg/dL, or apolipoprotein B ≥ 80 mg/dL; and treated with optimized lipid-lowering therapy. Patients were randomized in a 1:1 ratio to evolocumab 140 mg subcutaneously every 2 weeks or matching placebo. The primary efficacy objective is to assess whether evolocumab reduces the risk of the dual primary composite endpoints of coronary heart disease (CHD) death, myocardial infarction (MI), or ischemic stroke (triple primary endpoint) and of CHD death, MI, ischemic stroke, or ischemia-driven arterial revascularization (quadruple primary endpoint). Recruitment began in June 2019 and completed in November 2021. The trial is planned to continue until at least 751 patients experience an adjudicated triple endpoint, at least 1254 experience an adjudicated quadruple endpoint, and the median follow-up is ≥4.5 years.
Conclusion: VESALIUS-CV will determine whether the addition of evolocumab to optimized lipid-lowering therapy reduces cardiovascular events in patients at high cardiovascular risk without a prior MI or stroke.
Trial Registration: NCT03872401.
Competing Interests: Disclosures Drs. Bohula, Giugliano, Marston, Murphy and Sabatine are members of the TIMI Study Group. The TIMI Study Group reports grant support through Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc., Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Siemens Healthcare Diagnostics, Inc., Softcell Medical Limited, Verve Therapeutics, Zora Biosciences. Dr. Bohula reports personal fees from Kowa, Novo Nordisk, Servier and Esperion. Dr. Marston reports no personal fees. Dr. Leiter reports personal fees from Amarin, Amgen, AstraZeneca, HLS, Kowa, Merck, Pfizer, and Sanofi. Dr. Bhatia, Dr. Wang and Ms. Elliott-Davey are employees and stockholders of Amgen. Dr. Ruzza is former Amgen employee and stockholder, has a pending patent application PCT/US2021/034489 on PCSK9 inhibitors and methods of use thereof to treat cholesterol-related disorders, and is currently GSK employee and stockholder. Dr. Giugliano reports personal fees from Amgen, Daiichi-Sankyo, Dr. Reddy's Laboratories, Inventiva Pharma, Medical Education Resources, Pfizer, Sanofi, SUMMEET. Dr. Sabatine reports personal fees from Amgen; Anthos Therapeutics; AstraZeneca; Beren Therapeutics; Boehringer Ingelheim; Dr. Reddy's Laboratories; Fibrogen; Intarcia; Merck; Moderna; Novo Nordisk; Precision BioSciences; Silence Therapeutics.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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