Real-World Implementation of a Genotype-Guided P2Y12 Inhibitor De-Escalation Strategy in Acute Coronary Syndrome Patients

IF 11.7 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Cardiovascular interventions Pub Date : 2024-09-09 DOI:10.1016/j.jcin.2024.06.020

Jaouad Azzahhafi MD , Wout W.A. van den Broek MD , Dean R.P.P. Chan Pin Yin MD , Niels M.R. van der Sangen MD , Shabiga Sivanesan MD , Salahodin Bofarid MD , Joyce Peper MSc, PhD , Daniel M.F. Claassens MD, PhD , Paul W.A. Janssen MD, PhD , Ankie M. Harmsze PharmD, PhD , Ronald J. Walhout MD, PhD , Melvyn Tjon Joe Gin MD , Deborah M. Nicastia MD , Jorina Langerveld MD, PhD , Georgios J. Vlachojannis MD, PhD , Rutger J. van Bommel MD, PhD , Yolande Appelman MD, PhD , Ron H.N. van Schaik MSc, PhD , José P.S. Henriques MD, PhD , Wouter J. Kikkert MD, PhD , Jurriën M. ten Berg MD, PhD

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引用次数: 0

Abstract

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.

查看原文本刊更多论文

在急性冠状动脉综合征患者中实际实施基因型指导的 P2Y12 抑制剂去梗策略。

背景：在CYP2C19基因型指导下，从替卡格雷或普拉格雷降至氯吡格雷可优化急性冠脉综合征（ACS）患者缺血和出血风险之间的平衡：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：自2015年起，多中心FORCE-ACS（急性冠状动脉综合征患者未来最佳研究与护理评估）登记处的ACS患者接受标准双联抗血小板疗法（DAPT）。自2021年起，一个中心建议在基因型指导下进行P2Y12抑制剂降级，将非功能缺失等位基因CYP2C19∗3或CYP2C19∗2携带者从替卡格雷或普拉格雷换成氯吡格雷，而功能缺失携带者则继续使用替卡格雷或普拉格雷。对基因分型队列和接受标准 DAPT 治疗 1 年后的队列进行了主要缺血终点（心血管死亡率、心肌梗死或中风的复合终点）和主要出血终点（出血学术研究联盟 2、3 或 5 期出血）的比较：在5321名入选的ACS患者中，有406名接受了基因分型，而未接受基因分型的ACS患者中有4915名接受了标准DAPT治疗。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。在基因分型队列中，5.2%（n = 21）的患者出现主要缺血终点，而在标准治疗队列中，这一比例为 6.9%（n = 337）（调整后 HR：0.82；95% CI：0.53-1.28）。基因分型队列的原发性出血率明显低于标准护理队列（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，在真实世界的ACS人群中实施CYP2C19基因型指导的P2Y12抑制剂降级策略可降低出血率，同时不增加缺血事件。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JACC. Cardiovascular interventions CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

11.60

自引率

8.80%

发文量

756

审稿时长

4-8 weeks

期刊介绍： JACC: Cardiovascular Interventions is a specialist journal launched by the Journal of the American College of Cardiology (JACC). It covers the entire field of interventional cardiovascular medicine, including cardiac, peripheral, and cerebrovascular interventions. The journal publishes studies that will impact the practice of interventional cardiovascular medicine, including clinical trials, experimental studies, and in-depth discussions by respected experts. To enhance visual understanding, the journal is published both in print and electronically, utilizing the latest technologies.