依洛尤单抗对无既往心肌梗死或中风的高心血管风险患者的疗效（VESALIUS-CV）试验的原理与设计

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

作者信息

Bohula Erin A, Marston Nicholas A, Ruzza Andrea, Murphy Sabina A, De Ferrari Gaetano M, Diaz Rafael, Leiter Lawrence A, Elliott-Davey Mary, Wang Huei, Bhatia Ajay K, Giugliano Robert P, Sabatine Marc S

机构信息

TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

出版信息

Am Heart J. 2024 Mar;269:179-190. doi: 10.1016/j.ahj.2023.12.004. Epub 2023 Dec 29.

DOI:10.1016/j.ahj.2023.12.004

PMID:38160917

Abstract

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.

摘要

背景

依洛尤单抗是一种完全人源化的前蛋白转化酶枯草溶菌素/克新9型（PCSK9i）单克隆抗体抑制剂，用其降低低密度脂蛋白胆固醇（LDL-C）可降低已确诊的动脉粥样硬化性心血管疾病（ASCVD）且有心肌梗死（MI）病史、中风病史或有症状的外周动脉疾病患者发生主要不良心血管事件的风险，且不存在安全性顾虑。依洛尤单抗对无MI或中风病史的低风险患者心血管结局的影响尚未得到研究。

研究设计

VESALIUS-CV是一项随机、双盲、安慰剂对照的全球临床试验，旨在评估依洛尤单抗对心血管风险高但无既往缺血事件患者发生主要心血管事件风险的影响。研究人群包括12301例患有动脉粥样硬化或高危糖尿病且无既往MI或中风的患者；低密度脂蛋白胆固醇（LDL-C）≥90mg/dL，或非高密度脂蛋白胆固醇（non-HDL-C）≥120mg/dL，或载脂蛋白B≥80mg/dL；并接受了优化的降脂治疗。患者按1:1比例随机分为每2周皮下注射140mg依洛尤单抗组或匹配的安慰剂组。主要疗效目标是评估依洛尤单抗是否能降低冠心病（CHD）死亡、心肌梗死（MI）或缺血性中风（三联主要终点）以及CHD死亡、MI、缺血性中风或缺血驱动的动脉血运重建（四联主要终点）这两个主要复合终点的风险。招募工作于2019年6月开始，2021年11月完成。该试验计划持续至至少751例患者经历经判定的三联终点、至少1254例患者经历经判定的四联终点，且中位随访时间≥4.5年。