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对P2Y12抑制剂反应的遗传决定因素和临床影响
Larisa H Cavallari1, James C Coons2
1Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine, University of Florida, 1333 Center Drive, PO Box 100486, Gainesville, FL 32610, USA.
在CYP2C19的遗传变异影响克洛皮多格雷尔的激活,减少约30%的人的有效性. 对于这些遗传变异的个体,建议使用普拉苏格勒或提卡格勒尔等替代药物.
科学领域:
- 药物基因组学 药物基因组学
- 心脏病学 心脏病学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 克洛皮多格勒是需要 CYP2C19 酶激活的前药物.
- 在CYP2C19中功能丧失 (LoF) 多态影响大约30%的人口.
- 减少活性代谢物形成导致克洛皮多格雷尔有效性降低,特别是在心血管患者中.
研究的目的:
- 审查CYP2C19基因型对克洛皮多格雷尔疗效的影响.
- 要突出其他不受CYP2C19基因型影响的P2Y12抑制剂.
- 讨论CYP2C19引导的抗血小板治疗的临床影响.
主要方法:
- 对研究CYP2C19基因型和克洛皮多格雷尔反应的文献综述.
- 对有或没有CYP2C19LoF等位基因的患者的临床结果的分析.
- 在CYP2C19基因型群体中比较替代P2Y12抑制剂 (prasugrel,ticagrelor).
主要成果:
- 具有CYP2C19LoF等位基因的患者表现出克洛皮多格雷尔的有效性降低.
- 这种降低的疗效与急性冠状动脉综合征或皮肤冠状动脉干预后的不良结果有关.
- 普拉苏格勒和提卡格勒尔无论CYP2C19的基因型如何,都显示出一致的疗效.
结论:
- CYP2C19基因型显著影响克洛皮多格雷尔的反应和临床结果.
- 以CYP2C19为导向的P2Y12抑制剂选择方法可以改善患者的治疗结果.
- 需要更广泛地采用基因型鉴定,以优化相关患者群体的抗血小板治疗.
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