BACKGROUND CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS). OBJECTIVES This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care. METHODS Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1 year. RESULTS Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n = 265) were noncarriers, 88.7% (n = 235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n = 21) of patients in the genotyped cohort compared to 6.9% (n = 337) in the standard care cohort (adjusted HR: 0.82; 95% CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95% CI: 0.30-0.76). CONCLUSIONS The implementation of a CYP2C19 genotype-guided P2Y12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen.

中文翻译：

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在急性冠脉综合征患者中实际实施基因型引导的 P2Y12 抑制剂降级策略。


背景 CYP2C19 基因型引导从替格瑞洛或普拉格雷降级至氯吡格雷可能优化急性冠脉综合征 (ACS) 患者缺血和出血风险之间的平衡。目的 本研究旨在比较基因分型患者与标准治疗的出血和缺血事件发生率。方法 自 2015 年以来，多中心 FORCE-ACS（急性冠状动脉综合征患者的未来最佳研究和护理评估）登记处的 ACS 患者接受了标准双联抗血小板治疗 (DAPT)。自2021年起，建议在单中心进行基因型引导的P2Y12抑制剂降级，将功能丧失等位基因CYP2C19*3或CYP2C19*2的非携带者从替格瑞洛或普拉格雷切换为氯吡格雷，而功能丧失等位基因携带者则保留替格瑞洛或普拉格雷。主要缺血终点（心血管死亡率、心肌梗死或中风的综合）和主要出血终点（出血学术研究联盟 2、3 或 5 次出血）在基因分型队列和 1 年后接受标准 DAPT 治疗的队列之间进行了比较。年。结果 在 5,321 名入组 ACS 患者中，406 名患者接受了基因分型，而接受标准 DAPT 的未基因分型 ACS 患者为 4,915 名。在基因分型队列中，65.3% (n = 265) 为非携带者，其中 88.7% (n = 235) 改用氯吡格雷。基因分型队列中 5.2% (n = 21) 的患者发生主要缺血终点，而标准护理队列中这一比例为 6.9% (n = 337)（调整后 HR：0.82；95% CI：0.53-1.28）。与标准护理队列相比，基因分型队列的原发出血率显着降低（4.7% vs 9.8%；调整后 HR：0.47；95% CI：0.30-0.76）。 结论 与标准 DAPT 方案相比，在现实 ACS 人群中实施 CYP2C19 基因型引导的 P2Y12 抑制剂降阶梯策略可降低出血率，且不会增加缺血事件。