Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine, University of Florida, 1333 Center Drive, PO Box 100486, Gainesville, FL 32610, USA.
Department of Pharmacy and Therapeutics, Center for Clinical Pharmaceutical Sciences, University of Pittsburgh, 9058 Salk Hall, 3501 Terrace Street, Pittsburgh, PA 15261, USA.
Interv Cardiol Clin. 2024 Oct;13(4):469-481. doi: 10.1016/j.iccl.2024.06.002. Epub 2024 Aug 1.
The CYP2C19 enzyme metabolizes clopidogrel, a prodrug, to its active form. Approximately 30% of individuals inherit a loss-of-function (LoF) polymorphism in the CYP2C19 gene, leading to reduced formation of the active clopidogrel metabolite. Reduced clopidogrel effectiveness has been well documented in patients with an LoF allele following an acute coronary syndrome or percutaneous coronary intervention. Prasugrel or ticagrelor is recommended in those with an LoF allele as neither is affected by CYP2C19 genotype. Although data demonstrate improved outcomes with a CYP2C19-guided approach to P2Y inhibitor selection, genotyping has not yet been widely adopted in clinical practice.
CYP2C19 酶代谢氯吡格雷，一种前体药物，形成其活性形式。大约 30%的个体遗传 CYP2C19 基因的功能丧失（LoF）多态性，导致活性氯吡格雷代谢物的形成减少。在急性冠状动脉综合征或经皮冠状动脉介入治疗后，携带 LoF 等位基因的患者中，氯吡格雷的有效性已得到充分证实。对于携带 LoF 等位基因的患者，建议使用普拉格雷或替格瑞洛，因为这两种药物均不受 CYP2C19 基因型的影响。尽管数据表明 CYP2C19 指导的 P2Y 抑制剂选择方法可改善结局，但基因分型尚未在临床实践中广泛采用。
