Université de Paris, CIC1418 et DMU CARTE, Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
Ramsay Générale de Santé, ICPS, Massy, France.
JACC Cardiovasc Interv. 2020 Mar 9;13(5):621-630. doi: 10.1016/j.jcin.2020.01.219.
The aim of this study was to evaluate prospectively the clinical impact of routine transmission of CYP2C19 genotype in the management of acute ST-segment elevation myocardial infarction with primary percutaneous coronary intervention.
Response to clopidogrel differs widely among patients, notably because of CYP2C19 genetic polymorphisms.
CYP2C19 genotype (6 alleles) was determined centrally and communicated within 4.1 ± 1.9 days of primary percutaneous coronary intervention in 1,445 patients with ST-segment elevation myocardial infarction recruited at 57 centers in France. CYP2C19 metabolic status was predicted from genotype and served to adjust thienopyridine treatment. The primary endpoint was differences in 12-month outcomes (death, myocardial infarction, and stent thrombosis) between patients with the wild-type genotype or gain-of-function allele (class 1, n = 1,118) and those with loss-of-function (LOF) alleles (class 2, n = 272) who received optimized thienopyridine treatment.
Detection of LOF alleles resulted in adjustment of P2Y inhibition in 85% of patients, with significantly higher use of prasugrel or double-dose clopidogrel. The primary endpoint did not differ between class 1 and class 2 patients (3.31% vs. 3.04%, respectively; p = 0.82). In contrast, carriers of LOF alleles without treatment adjustment had significantly worse outcomes (15.6%; p < 0.05). Bleeding rates were not different between groups.
In a real-world setting, a complete CYPC2C19 genotype can be mostly determined in <7 days using analysis of saliva deoxyribonucleic acid collected during the in-hospital phase among patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Genotype information led to stronger platelet inhibition treatment in the vast majority of LOF allele carriers and to similar clinical outcomes as in patients carrying the wild-type genotype or gain-of-function allele. (Genotyping Infarct Patients to Adjust and Normalize Thienopyridine Treatment [GIANT]; NCT01134380).
本研究旨在前瞻性评估 CYP2C19 基因型常规检测在伴发 ST 段抬高的急性心肌梗死行直接经皮冠状动脉介入治疗（PCI）中的临床影响。
氯吡格雷的反应在患者间存在广泛差异，这主要归因于 CYP2C19 遗传多态性。
在法国 57 个中心共纳入 1445 例伴发 ST 段抬高的心肌梗死患者，于直接 PCI 后 4.1±1.9 天内行 CYP2C19 基因分型（6 个等位基因）检测，基因型信息由中心实验室统一测定并及时反馈。根据基因型预测 CYP2C19 代谢状态，调整噻吩吡啶类药物治疗。主要终点为携带野生型基因型或功能获得型等位基因（CYP2C19 功能分类 1 类，n=1118）与携带功能缺失型等位基因（CYP2C19 功能分类 2 类，n=272）的患者在接受优化噻吩吡啶类药物治疗后的 12 个月结局（死亡、心肌梗死和支架血栓形成）差异。
检测到功能缺失型等位基因时，85%的患者调整了 P2Y 抑制作用，显著增加了普拉格雷或氯吡格雷双剂量治疗的应用。1 类和 2 类患者的主要终点无差异（分别为 3.31%和 3.04%，p=0.82）。相反，未调整治疗的功能缺失型等位基因携带者结局更差（15.6%；p<0.05）。各组间出血发生率无差异。
在真实世界环境中，直接 PCI 治疗伴发 ST 段抬高的急性心肌梗死患者在住院期间采集唾液脱氧核糖核酸（DNA），7 天内可完成 CYP2C19 全基因检测。基因型信息可使绝大多数功能缺失型等位基因携带者接受更强的血小板抑制治疗，并获得与携带野生型基因型或功能获得型等位基因患者相似的临床结局。（Genotyping Infarct Patients to Adjust and Normalize Thienopyridine Treatment [GIANT]；NCT01134380）
