Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC USA.
Department of Pharmacotherapy & Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy, University of Florida Gainesville FL USA.
J Am Heart Assoc. 2024 Jun 18;13(12):e033791. doi: 10.1161/JAHA.123.033791. Epub 2024 Jun 14.
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 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.
Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical 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 <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], =0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups.
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.
细胞色素 P450 2C19（CYP2C19）中间代谢和弱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降低。然而，迄今为止的研究结果缺乏种族多样性。因此，在接受氯吡格雷治疗并自我认同为黑人或非裔美国人的患者中，基因型对心血管结局的影响仍不清楚。
来自 5 个机构的成年人自我认同为黑人或非裔美国人，接受了 PCI 和临床基因分型，并接受了氯吡格雷治疗。从健康记录中提取数据。使用多变量 Cox 回归分析，根据潜在混杂因素和基线变量调整，比较了 CYP2C19 代谢物组中 PCI 后 1 年内主要动脉血栓形成（死亡、心肌梗死、缺血性中风、支架血栓形成或不稳定型心绞痛血管重建的复合终点）和出血事件发生率。该人群包括 567 名接受氯吡格雷治疗的黑人患者（中位年龄 62 岁；46%为女性；70%为 PCI 的急性冠脉综合征指征）。氯吡格雷治疗的中间代谢和弱代谢患者的主要动脉血栓形成事件发生率明显高于无功能等位基因的氯吡格雷治疗患者（125 例中的 24 例[19.2%]与 442 例中的 43 例[9.7%]；每 100 人年 35.1 至 15.9 例事件；调整后的危险比，2.00 [95%CI，1.20-3.33]，=0.008）。总体出血事件发生率较低（567 例中的 23 例[4.1%]），且在代谢物组之间无差异。
在真实临床环境中，接受氯吡格雷治疗的 CYP2C19 中间代谢和弱代谢表型的黑人患者 PCI 后发生不良心血管结局的风险增加。出血结局应谨慎解释。需要前瞻性研究来确定在接受 PCI 的黑人患者中，中间代谢和弱代谢者使用普拉格雷或替格瑞洛的基因型指导是否改善结局。
