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Circulation：高PRS的CAD患者可从alirocumab治疗中明显获益

2020-03-01 QQY MedSci原创

PRSCADAlirocumab
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Alirocumab，一种阻断PCSK9(前蛋白转化酶枯草素/kexin 9型)的抗体；在ODYSSEY OUTCOMES试验中，与主要心血管不良事件(MACE)和死亡减少相关。在本研究中，较低密度脂蛋白胆固醇(LDL-C)的基线水平越高，预示Alirocumab的疗效越好。近期研究表明，冠状动脉疾病(CAD)的高多基因风险评分(PRS)可以鉴别出那些从他汀类药物中获益更多的高危个体。研究人员进行

Alirocumab，一种阻断PCSK9(前蛋白转化酶枯草素/kexin 9型)的抗体；在ODYSSEY OUTCOMES试验中，与主要心血管不良事件(MACE)和死亡减少相关。在本研究中，较低密度脂蛋白胆固醇(LDL-C)的基线水平越高，预示Alirocumab的疗效越好。近期研究表明，冠状动脉疾病(CAD)的高多基因风险评分(PRS)可以鉴别出那些从他汀类药物中获益更多的高危个体。研究人员进行了事后分析，以确定冠心病的高PRS是否能独立于基础LDL-C和其他已知的风险因素之外识别出较高风险的、能从alirocumab治疗中获益更多的个体。

ODYSSEY OUTCOMES是一个随机的、双盲的、安慰剂为对照的试验，在18 924位急性冠脉综合征和粥样硬化脂蛋白升高患者中对比Alirocumab和安慰剂。主要结点（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性心绞痛。对11 953例有可用DNA样本的患者的冠心病全基因组PRS（包含6 579 025个遗传变异）进行评估。

MACE在安慰剂组的发生率与CAD的PRS相关：高PRS患者 17.0%，低PRS患者 11.4%；该PRS相关性不能用基础LDL-C或其他已知的风险因素来解释。与安慰剂相比，Alirocumab对MACE绝对风险和相对风险的降低在高PRS患者中均多于低PRS患者。高PRS组和第PRS组采用Alirocumab治疗的绝对风险分别降低了6.0%和1.5%，相对风险分别降低了37%和13%。

CAD的高PRS与急性冠脉综合征后的复发性MACE风险增高有关，还与Alirocumab治疗的绝对和相对风险降低更大有关，为风险分层和精准医疗提供了一个独立的工具。

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    2020-04-28 linlin2312

    #ROC#

    0

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    2020-09-05 snf701207

    #mAb#

    0

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    2020-12-08 kzlchina

    #PRS#

    0

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    2020-03-03 30397604

    #Alirocumab#

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