Nguyen Anh B, Cavallari Larisa H, Rossi Joseph S, Stouffer George A, Lee Craig R
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, FL, United States.
Front Cardiovasc Med. 2022 Aug 23;9:991646. doi: 10.3389/fcvm.2022.991646. eCollection 2022.
Dual antiplatelet therapy with a P2Y inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin remains the standard of care for all patients undergoing percutaneous coronary intervention (PCI). It is well-established that patients carrying no function alleles have impaired capacity to convert clopidogrel into its active metabolite and thus, are at higher risk of major adverse cardiovascular events (MACE). The metabolism and clinical effectiveness of prasugrel and ticagrelor are not affected by genotype, and accumulating evidence from multiple randomized and observational studies demonstrates that genotype-guided antiplatelet therapy following PCI improves clinical outcomes. However, most antiplatelet pharmacogenomic outcome studies to date have lacked racial and ethnic diversity. In this review, we will (1) summarize current guideline recommendations and clinical outcome evidence related to genotype-guided antiplatelet therapy, (2) evaluate the presence of potential racial and ethnic disparities in the major outcome studies supporting current genotype-guided antiplatelet therapy recommendations, and (3) identify remaining knowledge gaps and future research directions necessary to advance implementation of this precision medicine strategy for dual antiplatelet therapy in diverse, real-world clinical settings.
使用P2Y抑制剂（氯吡格雷、普拉格雷或替格瑞洛）和阿司匹林进行双重抗血小板治疗仍然是所有接受经皮冠状动脉介入治疗（PCI）患者的标准治疗方案。众所周知，携带无功能等位基因的患者将氯吡格雷转化为其活性代谢物的能力受损，因此，发生主要不良心血管事件（MACE）的风险更高。普拉格雷和替格瑞洛的代谢及临床疗效不受基因型影响，多项随机和观察性研究积累的证据表明，PCI术后基于基因型的抗血小板治疗可改善临床结局。然而，迄今为止，大多数抗血小板药物基因组学结局研究缺乏种族和民族多样性。在本综述中，我们将（1）总结当前与基于基因型的抗血小板治疗相关的指南建议和临床结局证据，（2）评估支持当前基于基因型的抗血小板治疗建议的主要结局研究中潜在的种族和民族差异，以及（3）确定在不同的真实世界临床环境中推进这种双重抗血小板治疗精准医学策略实施所需的剩余知识空白和未来研究方向。
