Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno- S, Allende street, 84081, Baronissi, Salerno, Italy.
Clinical Pharmacology and Pharmacogenetics Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", via S. Leonardo 1, Salerno, Italy.
Pharmacogenomics J. 2021 Apr;21(2):116-127. doi: 10.1038/s41397-020-00189-2. Epub 2020 Oct 9.
Patients bearing polymorphisms termed CYP2C19 loss of function (LoF) alleles and ABCB1-C3435T may do not properly respond to standard dosage of clopidogrel and have an increased risk of thrombosis. Moreover, co-administration of proton pump inhibitors (PPIs) and clopidogrel may attenuate the antiplatelet effect. The role of pharmacogenetics and PPIs/clopidogrel drug-drug interaction has been extensively investigated in patients with acute coronary syndrome after stent implantation (ACS/PCI), while data in patients undergoing vascular surgery are scarce. Here we have performed a systematic review to evaluate the available literature in such a clinical setting and have discussed the controversies about the use of CYP2C19 pharmacogenetics and platelet function testing to personalize clopidogrel treatment. In addition, we have made a comparison of the literature data with our findings concerning patients eligible for vascular surgery and treated with clopidogrel, in whom we used a combined management based on the CYP2C19 and ABCB1 pharmacogenetic testing with monitoring of therapeutic adherence and PPIs-clopidogrel interaction. Both our data and those produced during both observational studies and randomized clinical trials confirm the validity of pharmacogenetics to personalize clopidogrel treatment and stress the importance to make a drug monitoring considering all the known variables, potentially responsible for treatment failure. However, the American Heart Association and the European Cardiovascular Society recommend against the routine use of clopidogrel pharmacogenetic testing. An update of the international guidelines on antiplatelet therapy, incorporating the evidence related to CYP2C19 pharmacogenetics and PPIs-clopidogrel drug-drug interactions is warranted both in ACS/PCI patients and subjects undergoing vascular surgery.
携带被称为 CYP2C19 失活（LoF）等位基因和 ABCB1-C3435T 的多态性的患者可能无法对氯吡格雷的标准剂量做出适当反应，并且血栓形成的风险增加。此外，质子泵抑制剂（PPIs）和氯吡格雷的联合用药可能会减弱抗血小板作用。在接受支架植入术（ACS/PCI）后的急性冠脉综合征（ACS/PCI）患者中，已经广泛研究了药物遗传学和 PPI/氯吡格雷药物相互作用的作用，而在接受血管手术的患者中，相关数据却很少。在这里，我们进行了系统评价，以评估此类临床环境中的现有文献，并讨论了关于 CYP2C19 药物遗传学和血小板功能检测用于个体化氯吡格雷治疗的争议。此外，我们还将文献数据与我们在适合血管手术并接受氯吡格雷治疗的患者中发现的数据进行了比较，在这些患者中，我们使用了基于 CYP2C19 和 ABCB1 药物遗传学检测的联合管理，同时监测治疗依从性和 PPI-氯吡格雷相互作用。我们的数据以及观察性研究和随机临床试验产生的数据均证实了药物遗传学在个体化氯吡格雷治疗中的有效性，并强调了考虑所有已知变量（可能导致治疗失败）进行药物监测的重要性。然而，美国心脏协会和欧洲心血管学会不建议常规使用氯吡格雷药物遗传学检测。需要更新有关抗血小板治疗的国际指南，将与 CYP2C19 药物遗传学和 PPI-氯吡格雷药物相互作用相关的证据纳入其中，这不仅适用于 ACS/PCI 患者，也适用于接受血管手术的患者。
