Gower Megan N, Ratner Lindsay R, Williams Alexis K, Rossi Joseph S, Stouffer George A, Lee Craig R
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
Division of Cardiology, UNC School of Medicine, Chapel Hill, NC, USA.
Pharmgenomics Pers Med. 2020 Jul 27;13:239-252. doi: 10.2147/PGPM.S231475. eCollection 2020.
In patients undergoing percutaneous coronary intervention (PCI), the standard of care is dual antiplatelet therapy with a P2Y inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin. Current clinical practice guidelines now recommend more potent P2Y inhibitors (prasugrel or ticagrelor) over clopidogrel in acute coronary syndrome (ACS). However, clopidogrel remains the most commonly prescribed P2Y inhibitor in the setting of PCI and is also the preferred agent in the treatment and secondary prevention of stroke. Clopidogrel is a prodrug that requires bioactivation by the CYP2C19 enzyme. It has been shown that clopidogrel use in patients who are CYP2C19 no function allele carriers are associated with impaired antiplatelet inhibition and a higher risk of major adverse cardiovascular and cerebrovascular events. Compared to clopidogrel, prasugrel and ticagrelor clinical response is not impacted by CYP2C19 genotype. Even with a demonstrated increased risk of adverse outcomes in CYP2C19 no function allele carriers treated with clopidogrel, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial and has not been widely adopted. Recent results from multiple prospective randomized and nonrandomized clinical trials investigating the use of CYP2C19 genotype-guided antiplatelet therapy following PCI have advanced the evidence base demonstrating the clinical utility of this strategy. Multiple recent studies have examined the effects of CYP2C19 genotype on clopidogrel outcomes in the setting of stroke and neurointerventional procedures. In this review, we discern the clinical utility of using CYP2C19 genotype testing to guide antiplatelet therapy prescribing by evaluating the impact of CYP2C19 genotype-guided selection of antiplatelet therapy on clinical outcomes, summarizing emerging data from cardiovascular and neurology clinical studies, and discussing implications for clinical practice guidelines, remaining knowledge gaps and future research directions.
在接受经皮冠状动脉介入治疗（PCI）的患者中，标准治疗方案是使用P2Y12抑制剂（氯吡格雷、普拉格雷或替格瑞洛）和阿司匹林进行双联抗血小板治疗。目前的临床实践指南现在推荐在急性冠状动脉综合征（ACS）中使用更强效的P2Y12抑制剂（普拉格雷或替格瑞洛）而非氯吡格雷。然而，氯吡格雷仍是PCI中最常用的P2Y12抑制剂，也是中风治疗和二级预防的首选药物。氯吡格雷是一种前体药物，需要通过CYP2C19酶进行生物活化。已有研究表明，在携带CYP2C19无功能等位基因的患者中使用氯吡格雷与抗血小板抑制受损以及发生主要不良心血管和脑血管事件的风险较高相关。与氯吡格雷相比，普拉格雷和替格瑞洛的临床反应不受CYP2C19基因型的影响。即使在用氯吡格雷治疗的CYP2C19无功能等位基因携带者中已证实不良结局风险增加，但常规实施CYP2C19基因分型以指导抗血小板治疗选择仍存在争议，尚未被广泛采用。多项前瞻性随机和非随机临床试验关于PCI后使用CYP2C19基因型指导抗血小板治疗的最新结果推进了证据基础，证明了该策略的临床实用性。最近的多项研究探讨了CYP2C19基因型对中风和神经介入手术中氯吡格雷疗效的影响。在本综述中，我们通过评估CYP2C19基因型指导的抗血小板治疗选择对临床结局的影响、总结心血管和神经学临床研究的新数据以及讨论对临床实践指南的影响、尚存的知识空白和未来研究方向，来识别使用CYP2C19基因型检测指导抗血小板治疗处方的临床实用性。
