PDF(Pubmed)
Abstract：
BACKGROUND: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.
RESULTS: Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P<0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], P=0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups.
CONCLUSIONS: Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.
RESULTS: Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P<0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], P=0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups.
CONCLUSIONS: Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.
摘要：
背景：细胞色素P4502C19（CYP2C19）中间和低代谢患者在经皮冠状动脉介入治疗（PCI）后表现出氯吡格雷临床疗效下降。然而,迄今为止的结局研究缺乏种族多样性.因此，CYP2C19基因型对氯吡格雷治疗的黑人或非洲裔患者心血管结局的影响尚不清楚.
结果：5个自我认定为黑人或非裔美国人的机构中的成年人，接受PCI和临床CYP2C19基因分型，并接受氯吡格雷治疗。数据是从健康记录中提取的。主要动脉粥样硬化血栓形成（复合死亡，心肌梗塞,缺血性卒中,支架内血栓形成,或不稳定型心绞痛的血运重建)和PCI后1年内出血事件发生率在CYP2C19代谢组之间进行比较,使用多变量Cox回归校正潜在混杂因素,基线变量达到P<0.10的阈值.人群包括567名接受氯吡格雷治疗的Black患者(中位年龄，62岁；46%的女性；70%的患者有急性冠脉综合征的PCI指征）。主要动脉粥样硬化血栓形成事件发生率在接受氯吡格雷治疗的中重度和低代谢患者中（125例中的24例[19.2%]）明显高于接受氯吡格雷无无无功能等位基因治疗的患者（442例中的43例[9.7%]；每100人年发生35.1例与15.9例；调整后的风险比，2.00[95%CI，1.20-3.33]，P=0.008)。总体上出血事件发生率较低（567例中的23例[4.1%]），代谢组之间没有差异。
结论：在真实世界的临床环境中，接受氯吡格雷治疗的CYP2C19中间和低代谢表型的Black患者在PCI后出现不良心血管结局的风险增加。出血结果应谨慎解释。需要进行前瞻性研究，以确定在中度和代谢不良者中基因型指导使用普拉格雷或替格瑞洛是否可以改善接受PCI的Black患者的预后。
结果：5个自我认定为黑人或非裔美国人的机构中的成年人，接受PCI和临床CYP2C19基因分型，并接受氯吡格雷治疗。数据是从健康记录中提取的。主要动脉粥样硬化血栓形成（复合死亡，心肌梗塞,缺血性卒中,支架内血栓形成,或不稳定型心绞痛的血运重建)和PCI后1年内出血事件发生率在CYP2C19代谢组之间进行比较,使用多变量Cox回归校正潜在混杂因素,基线变量达到P<0.10的阈值.人群包括567名接受氯吡格雷治疗的Black患者(中位年龄，62岁；46%的女性；70%的患者有急性冠脉综合征的PCI指征）。主要动脉粥样硬化血栓形成事件发生率在接受氯吡格雷治疗的中重度和低代谢患者中（125例中的24例[19.2%]）明显高于接受氯吡格雷无无无功能等位基因治疗的患者（442例中的43例[9.7%]；每100人年发生35.1例与15.9例；调整后的风险比，2.00[95%CI，1.20-3.33]，P=0.008)。总体上出血事件发生率较低（567例中的23例[4.1%]），代谢组之间没有差异。
结论：在真实世界的临床环境中，接受氯吡格雷治疗的CYP2C19中间和低代谢表型的Black患者在PCI后出现不良心血管结局的风险增加。出血结果应谨慎解释。需要进行前瞻性研究，以确定在中度和代谢不良者中基因型指导使用普拉格雷或替格瑞洛是否可以改善接受PCI的Black患者的预后。
