Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Clin Transl Sci. 2024 Aug;17(8):e70004. doi: 10.1111/cts.70004.
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population.
双重抗血小板治疗（DAPT）联合阿司匹林和 P2Y 受体抑制剂（氯吡格雷、普拉格雷或替格瑞洛）适用于经皮冠状动脉介入治疗（PCI）后，以降低动脉粥样硬化血栓形成事件的风险。大约 30%的美国人口存在 CYP2C19 无功能等位基因，该等位基因降低了 PCI 后氯吡格雷的疗效，但不降低普拉格雷或替格瑞洛的疗效。我们已经表明，通过整合 CYP2C19 基因分型到临床护理中，以指导 CYP2C19 无功能等位基因携带者选择普拉格雷或替格瑞洛，可以改善结局。然而，在基因型指导的 DAPT 中，患者特定的人口统计学、临床和其他遗传因素对结局的影响尚未确定。此外，在不同的真实临床环境中，对于没有 CYP2C19 无功能等位基因的患者，从普拉格雷或替格瑞洛基因型指导降级为氯吡格雷对结局的影响尚未进行研究。经皮冠状动脉介入治疗后精准抗血小板治疗（Precision PCI）注册研究是一项在美国进行的多中心注册研究，纳入了接受 PCI 和临床 CYP2C19 检测的患者。该注册研究正在招募不同人群，评估 12 个月内的动脉粥样硬化血栓形成和出血事件，收集 DNA 样本，并在部分患者中进行血小板功能检测。该注册研究旨在确定 CYP2C19 指导的 DAPT 中非洲裔和其他患者特定因素对临床结局的影响，评估 CYP2C19 指导的 PCI 后 DAPT 降级的安全性和有效性，以及确定 PCI 后氯吡格雷反应的其他遗传影响，最终目标是建立优化的个体化抗血小板治疗策略，改善不同真实世界人群的结局。
