Patel Rajiv C, Thomas Cameron D, Rossi Joseph S, Franchi Francesco, Keeley Ellen C, Beitelshees Amber L, Duarte Julio D, Ortega-Paz Luis, Kulick Natasha, Winget Marshall, Nguyen Anh B, Yang William E, Venkatesh Sanjay, Angiolillo Dominick J, Cavallari Larisa H, Lee Craig R, Stouffer George A
Division of Cardiology and McAllister Heart Institute, School of Medicine 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. 2025 Jul 15;14(14):e041634. doi: 10.1161/JAHA.125.041634. Epub 2025 Jul 3.
Use of genotyping to guide antiplatelet therapy is associated with improved clinical outcomes in patients naïve to P2Y inhibitors undergoing percutaneous coronary intervention. The relationship between genotype and clinical outcomes in patients on maintenance clopidogrel at the time of percutaneous coronary intervention is unknown.
This was a retrospective, multicenter cohort study. Patients were characterized as intermediate or poor metabolizers versus normal or rapid or ultrarapid metabolizers on the basis of genotype. Major adverse cardiovascular events included cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis.
The study population (N=4246) had a median age of 63.0 (interquartile range, 55.0-71.0) years, was 66.8% men, and 21.3% Black individuals. During 12-month follow-up, major adverse cardiovascular event rates were higher (7.4% versus 4.8%; <0.001) in the maintenance clopidogrel cohort (n=879) compared with the P2Y inhibitor naïve cohort (n=3367). In weighted Cox regression models of the maintenance clopidogrel cohort, major adverse cardiovascular event risk did not significantly differ in the clopidogrel-treated intermediate/poor metabolizer group versus clopidogrel-treated normal/rapid/UM metabolizer group (hazard ratio [HR], 0.88 [95% CI, 0.41-1.86]) versus the prasugrel- or ticagrelor-treated group (HR, 0.73 [95% CI, 0.28-1.87]), although the confidence intervals were wide. In contrast, weighted major adverse cardiovascular events risk in the P2Y inhibitor naïve cohort was higher in the clopidogrel-treated intermediate or poor metabolizers group compared with clopidogrel-treated normal/rapid/ultrarapid metabolizer group or prasugrel- or ticagrelor-treated group.
Patients on maintenance clopidogrel at the time of percutaneous coronary intervention represent a higher-risk patient population than patients who are naïve to P2Y inhibitors and genotype-guided P2Y inhibitor selection at the time of percutaneous coronary intervention may not provide clinical benefit.
对于接受经皮冠状动脉介入治疗且未使用过P2Y抑制剂的患者，采用基因分型指导抗血小板治疗与改善临床结局相关。在接受经皮冠状动脉介入治疗时正在服用氯吡格雷维持治疗的患者中，基因分型与临床结局之间的关系尚不清楚。
这是一项回顾性多中心队列研究。根据基因分型，将患者分为中间代谢型或慢代谢型，以及正常代谢型、快代谢型或超快代谢型。主要不良心血管事件包括心血管死亡、心肌梗死、缺血性卒中或支架血栓形成。
研究人群（N = 4246）的中位年龄为63.0（四分位间距，55.0 - 71.0）岁，男性占66.8%，黑人占21.3%。在12个月的随访期间，正在服用氯吡格雷维持治疗的队列（n = 879）中的主要不良心血管事件发生率高于未使用过P2Y抑制剂的队列（n = 3367）（7.4%对4.8%；P < 0.001）。在正在服用氯吡格雷维持治疗队列的加权Cox回归模型中，氯吡格雷治疗的中间代谢型/慢代谢型组与氯吡格雷治疗的正常代谢型/快代谢型/超快代谢型组相比，主要不良心血管事件风险无显著差异（风险比[HR]，0.88[95%CI，0.41 - 1.86]），与普拉格雷或替格瑞洛治疗组相比（HR，0.73[95%CI，0.28 - 1.87]），尽管置信区间较宽。相比之下，在未使用过P2Y抑制剂的队列中，氯吡格雷治疗的中间代谢型或慢代谢型组的加权主要不良心血管事件风险高于氯吡格雷治疗的正常代谢型/快代谢型/超快代谢型组或普拉格雷或替格瑞洛治疗组。
在接受经皮冠状动脉介入治疗时正在服用氯吡格雷维持治疗的患者比未使用过P2Y抑制剂的患者属于更高风险的人群，并且在经皮冠状动脉介入治疗时采用基因分型指导选择P2Y抑制剂可能无法带来临床获益。
