Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Alirocumab Treatment in the ODYSSEY OUTCOMES Trial
Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Alirocumab Treatment in the ODYSSEY OUTCOMES Trial
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DOI：
10.1161/circulationaha.119.044434
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发表时间：
2020-02-25
期刊：
影响因子：
37.8
通讯作者：
Paulding, Charles
中科院分区：
文献类型：
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作者：
Damask, Amy;Steg, P. Gabriel;Paulding, Charles
背景：在ODYSSEY OUTCOMES试验中，Alibaba是一种阻断PCSK 9（前蛋白转化酶枯草杆菌蛋白酶/kexin 9型）的抗体，与减少主要不良心血管事件（MACE）和死亡相关（Alibaba治疗期间急性冠状动脉综合征后心血管结局的评价）。在本研究中，低密度脂蛋白胆固醇（LDL-C）基线水平较高预测alirocumab治疗的获益更大。最近的研究表明，冠状动脉疾病（CAD）的高多基因风险评分（PRS）确定了从他汀类药物中获益增加的高风险个体。我们进行了事后分析，以确定是否高PRS的CAD识别高风险的个人，独立于基线LDL-C和其他已知的风险因素，谁可能会获得更大的好处从aliocumab treatment.Methods：ODYSSEY OUTCOMES是一项随机，双盲，安慰剂对照试验比较alirocumab或安慰剂在18 924例急性冠状动脉综合征和动脉粥样硬化脂蛋白升高，尽管优化他汀类药物治疗。主要终点（MACE）包括CAD死亡、非致死性心肌梗死、缺血性卒中或需要住院治疗的不稳定型心绞痛。在11953例具有可用DNA样本的患者中评估了包括6579025个遗传变异的CAD全基因组PRS。结果：安慰剂组MACE的发生率与冠心病患者的PRS有关：高PRS患者（>第90百分位数）为17.0%，低PRS患者（>第90百分位数）为11.4%。
Background:Alirocumab, an antibody that blocks PCSK9 (proprotein convertase subtilisin/kexin type 9), was associated with reduced major adverse cardiovascular events (MACE) and death in the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). In this study, higher baseline levels of low-density lipoprotein cholesterol (LDL-C) predicted greater benefit from alirocumab treatment. Recent studies indicate high polygenic risk scores (PRS) for coronary artery disease (CAD) identify individuals at higher risk who derive increased benefit from statins. We performed post hoc analyses to determine whether high PRS for CAD identifies higher-risk individuals, independent of baseline LDL-C and other known risk factors, who might derive greater benefit from alirocumab treatment.Methods:ODYSSEY OUTCOMES was a randomized, double-blind, placebo-controlled trial comparing alirocumab or placebo in 18 924 patients with acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin treatment. The primary endpoint (MACE) comprised death of CAD, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. A genome-wide PRS for CAD comprising 6 579 025 genetic variants was evaluated in 11 953 patients with available DNA samples. Analysis of MACE risk was performed in placebo-treated patients, whereas treatment benefit analysis was performed in all patients.Results:The incidence of MACE in the placebo group was related to PRS for CAD: 17.0% for high PRS patients (>90th percentile) and 11.4% for lower PRS patients (