Background

In the Asian population, the presence of the CYP2C19 loss-of-function (LOF) allele is a known genetic variation. This allele is associated with a reduced capacity to metabolize clopidogrel into its active forms through the CYP2C19 enzyme, resulting in diminished platelet inhibition and an elevated risk of recurrent cardiovascular events. Regulatory authorities have recommended an alternative P2Y12 inhibitor, ticagrelor, for individuals carrying the LOF allele. Consequently, this study seeks to assess the impact of the CYP2C19 genotype on the Platelet reactivity index (PRI) using a rapid genetic testing approach in Asian patients with chronic coronary syndromes (CCS) who undergo percutaneous coronary intervention (PCI).

Methods

This prospective study employed a parallel design, single-center design, and randomized approach. Genotyping for the CYP2C19*2 and *3 polymorphisms was conducted using the Nested Allele-Specific Multiplex PCR (NASM-PCR) technique. Patients meeting the inclusion criteria underwent genotyping for CYP2C19 polymorphisms. Following PCI, patients were randomly assigned to receive either ticagrelor or clopidogrel. PRI assessments were performed four hours after loading dose administration. The trial was registered with ClinicalTrials.gov under the identifier NCT05516784.

Results

Among the 94 patients recruited for the study, 40 (42.55%) were identified as carriers of the LOF allele for CYP2C19*2 and *3 (*1/*2, *2/*2, *1/*3). Out of the 84 patients evaluated for PRI (44 receiving clopidogrel and 40 receiving ticagrelor), 21 (47.7%) of the clopidogrel group and 39 (97.5%) of the ticagrelor group exhibited a favorable response to antiplatelet therapy (PRI < 50). Patients treated with ticagrelor demonstrated superior antiplatelet responses compared to those receiving clopidogrel, regardless of LOF carrier status (P = 0.005 and < 0.001 for non-LOF and LOF carriers, respectively).

Conclusion

NASM-PCR as a rapid genetic test holds promise for personalizing antiplatelet therapy in Asian CCS patients.

中文翻译：

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CYP2C19 基因型对接受经皮冠状动脉介入治疗 (PCI) 的慢性冠状动脉综合征 (CCS) 患者血小板反应指数 (PRI) 的影响：快速基因检测的影响

背景

在亚洲人群中，CYP2C19 功能丧失 (LOF) 等位基因的存在是一种已知的遗传变异。该等位基因与通过 CYP2C19 酶将氯吡格雷代谢为其活性形式的能力降低相关，从而导致血小板抑制减弱和心血管事件复发的风险升高。监管机构建议携带 LOF 等位基因的个体使用另一种 P2Y12 抑制剂替格瑞洛。因此，本研究旨在利用快速基因检测方法，对接受经皮冠状动脉介入治疗 (PCI) 的亚洲慢性冠状动脉综合征 (CCS) 患者评估 CYP2C19 基因型对血小板反应指数 (PRI) 的影响。

方法

这项前瞻性研究采用了平行设计、单中心设计和随机方法。使用巢式等位基因特异性多重 PCR (NASM-PCR) 技术对 CYP2C19*2 和 *3 多态性进行基因分型。符合纳入标准的患者接受了 CYP2C19 多态性基因分型。PCI 后，患者被随机分配接受替格瑞洛或氯吡格雷治疗。负荷剂量给药后四小时进行 PRI 评估。该试验已在 ClinicalTrials.gov 注册，标识符为 NCT05516784。

结果

在本研究招募的 94 名患者中，40 名 (42.55%) 被确定为 CYP2C19*2 和 *3 (*1/*2、*2/*2、*1/*3) LOF 等位基因的携带者。在接受 PRI 评估的 84 名患者中（44 名接受氯吡格雷，40 名接受替格瑞洛），氯吡格雷组有 21 名患者（47.7%），替格瑞洛组有 39 名患者（97.5%）表现出抗血小板治疗良好反应（PRI < 50）。与接受氯吡格雷治疗的患者相比，接受替格瑞洛治疗的患者表现出更好的抗血小板反应，无论 LOF 携带者状态如何（ 非 LOF 和 LOF 携带者分别P = 0.005 和 < 0.001）。

结论

NASM-PCR 作为一种快速基因检测有望为亚洲 CCS 患者提供个性化抗血小板治疗。