Medicina III Ospedale San Paolo, Dipartimento di Medicina, Chirurgia e Odontoiatria, Università degli Studi di Milano, Milan, Italy.
J Cardiovasc Med (Hagerstown). 2013 Dec;14 Suppl 1:S16-21. doi: 10.2459/JCM.0b013e328364bd3a.
Clopidogrel, a pro-drug whose active metabolite is an inhibitor of the platelet P2Y12 receptor, is used mostly for the prevention of cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary interventions. However, clopidogrel is associated with great variability in antiplatelet response, mostly caused by variable efficacy of cytochrome P450 (CYP) isoforms, which convert clopidogrel to its active metabolite in a two-step process. Tailored treatment regimens that aim to transform all poor responders into responders have been proposed as a solution to poor responsiveness to clopidogrel. This tailored treatment is based on laboratory tests of platelet function (such as platelet aggregometry, the vasodilator-stimulated phosphoprotein phosphorylation assay and the VerifyNow P2Y12 assay) or genotyping of CYP. However, currently there is no agreement among platelet function tests in the identification of poor responders; moreover, no standardization of these tests or guidance on how to tailor treatment effectively based on their results is available. The alternative of identifying poor responders based on CYP genotyping is also unsatisfactory, as CYP genotypes account for only about 10% of individual response to the drug. Therefore, tailoring treatment of clopidogrel should not be implemented in the clinical setting yet.
氯吡格雷是一种前体药物，其活性代谢物是血小板 P2Y12 受体抑制剂，主要用于经皮冠状动脉介入治疗的急性冠脉综合征患者预防心血管事件。然而，氯吡格雷的抗血小板反应存在很大的变异性，主要是由于细胞色素 P450（CYP）同工酶的疗效不同，CYP 同工酶在两步过程中将氯吡格雷转化为其活性代谢物。有人提出了针对所有低反应者的个体化治疗方案，以解决氯吡格雷反应不良的问题。这种个体化治疗基于血小板功能的实验室检测（如血小板聚集检测、血管扩张刺激磷蛋白磷酸化检测和 VerifyNow P2Y12 检测）或 CYP 基因分型。然而，目前在识别低反应者方面，血小板功能检测之间没有达成共识；此外，这些检测方法没有标准化，也没有关于如何根据检测结果有效地进行个体化治疗的指导。基于 CYP 基因分型来识别低反应者的替代方法也不尽如人意，因为 CYP 基因型仅占药物个体反应的约 10%。因此，氯吡格雷的个体化治疗目前还不能应用于临床实践。
