Genotype-Guided P2Y₁₂-Inhibitor De-Escalation Strategy in Acute Coronary Syndrome: Observational Evidence From the POPular-GUIDE PCI.

IF 7.2 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation: Cardiovascular Interventions Pub Date : 2026-05-01 Epub Date: 2026-02-26 DOI:10.1161/CIRCINTERVENTIONS.125.016084

Wout W A van den Broek, Jaouad Azzahhafi, Qiu Ying F van de Pol, Dean R P P Chan Pin Yin, Niels M R van der Sangen, Shabiga Sivanesan, J Peper, Ankie M Harmsze, Ronald J Walhout, Melvyn Tjon Joe Gin, Nicoline J Breet, Jorina Langerveld, Yolande Appelman, Ron H N van Schaik, José P S Henriques, Wouter J Kikkert, Jurriën M Ten Berg

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引用次数: 0

Abstract

Background: A genotype-guided de-escalation strategy-switching from a potent P2Y₁₂ inhibitor to clopidogrel-may reduce bleeding risk in patients with acute coronary syndrome. This analysis evaluated the safety and effectiveness of routine genetic testing to guide antiplatelet therapy in clinical practice.

Methods: In this investigator-initiated, prospective, multicenter implementation study, patients received either standard care, with antiplatelet therapy at the physician discretion, or genotype-guided therapy. In the genotype-guided group, physicians were recommended to switch to clopidogrel in noncarriers of CYP2C19 loss-of-function alleles. The coprimary end points were major adverse cardiac events, a composite of cardiovascular death, myocardial infarction, or stroke, and major or nonmajor clinically relevant bleeding, at 1 year of follow-up. Hazard ratios were adjusted for baseline differences between cohorts using multivariable Cox regression. Net adverse cardiac events comprised all-cause death, myocardial infarction, stroke, stent thrombosis, and major bleeding. A Bonferroni-adjusted significance level of α=0.025 was applied.

Results: A total of 9907 patients were included in the analysis. Of these, 1208 (12%) were included in the genotype-guided cohort, whereas 8699 (88%) were assigned to the standard care cohort. Major adverse cardiac events occurred in 107 patients (8.9%) in the genotype-guided cohort and 897 patients (10.3%) in the standard care cohort (adjusted hazard ratio, 1.05 [95% CI, 0.85-1.29]; P=0.64). Major or nonmajor clinically relevant bleeding was reported in 146 patients (12.1%) in the genotype-guided cohort compared with 1384 patients (15.9%) in the standard care cohort (adjusted hazard ratio, 0.79 [95% CI, 0.67-0.94]; P=0.01). There was no significant association with net adverse cardiac events (adjusted hazard ratio, 0.91 [95% CI, 0.76-1.09]; P=0.31).

Conclusions: In patients with acute coronary syndrome receiving antiplatelet therapy, implementation of a CYP2C19 genotype-guided de-escalation strategy in clinical practice was associated with a significant reduction of major and nonmajor clinically relevant bleeding compared with standard care at 12 months, without increasing ischemic events.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03823547.

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基因型引导的p2y12抑制剂在急性冠脉综合征中的降级策略：来自POPular-GUIDE PCI的观察证据

背景：基因型导向的降压策略——从强效P2Y12抑制剂切换到氯吡格雷——可能降低急性冠脉综合征（ACS）患者的出血风险。本分析评估了常规基因检测在临床实践中指导抗血小板治疗的安全性和有效性。方法：在这项研究者发起的、前瞻性的、多中心实施的研究中，患者接受标准治疗，在医生的判断下接受抗血小板治疗，或基因型指导治疗。在基因型引导组中，建议医生对CYP2C19功能缺失等位基因非携带者改用氯吡格雷。主要终点是1年随访时的主要心脏不良事件，心血管死亡、心肌梗死或中风的复合，以及主要或非主要临床相关出血。使用多变量Cox回归调整队列间基线差异的风险比。净不良心脏事件包括全因死亡、心肌梗死、中风、支架血栓形成和大出血。采用bonferroni校正显著性水平α=0.025。结果：共纳入9907例患者。其中，1208例（12%）被纳入基因型引导队列，而8699例（88%）被分配到标准治疗队列。基因型引导组107例（8.9%）患者发生严重心脏不良事件，标准治疗组897例（10.3%）患者发生严重心脏不良事件（校正风险比1.05 [95% CI, 0.85-1.29]； P=0.64）。基因型引导队列中有146例（12.1%）患者报告了重大或非重大临床相关出血，而标准治疗队列中有1384例（15.9%）患者报告了重大或非重大临床相关出血（校正风险比为0.79 [95% CI, 0.67-0.94]； P=0.01）。与净不良心脏事件无显著关联（校正风险比为0.91 [95% CI, 0.76-1.09]； P=0.31）。结论：在接受抗血小板治疗的急性冠状动脉综合征患者中，与标准治疗相比，在临床实践中实施CYP2C19基因型指导的降压策略与12个月时重大和非重大临床相关出血的显著减少相关，且未增加缺血性事件。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT03823547。

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来源期刊

Circulation: Cardiovascular Interventions CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

10.30

自引率

1.80%

发文量

221

审稿时长

6-12 weeks

期刊介绍： Circulation: Cardiovascular Interventions, an American Heart Association journal, focuses on interventional techniques pertaining to coronary artery disease, structural heart disease, and vascular disease, with priority placed on original research and on randomized trials and large registry studies. In addition, pharmacological, diagnostic, and pathophysiological aspects of interventional cardiology are given special attention in this online-only journal.