Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Division of Cardiology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Genet Med. 2020 Jan;22(1):160-169. doi: 10.1038/s41436-019-0611-1. Epub 2019 Jul 18.
To evaluate the frequency and clinical impact of switches in antiplatelet therapy following implementation of CYP2C19 genotyping after percutaneous coronary intervention (PCI).
The frequency of escalation (clopidogrel switched to prasugrel/ticagrelor) and de-escalation (prasugrel/ticagrelor switched to clopidogrel) was evaluated in 1063 PCI patients who underwent CYP2C19 genotyping. Risk of major adverse cardiovascular or cerebrovascular (MACCE) and bleeding events over one year was evaluated.
Antiplatelet therapy switches were common (19%), with escalation (101/115: 88%) and de-escalation (77/84: 92%) occurring predominantly in patients with and without a CYP2C19 nonfunctional allele, respectively. Nonfunctional allele carriers initiated and continued on clopidogrel had a significantly higher risk of experiencing either a MACCE or bleeding event compared with those escalated to prasugrel/ticagrelor (52 vs. 19 events/100 patient-years; adjusted hazard ratio [HR] 2.89 [1.44-6.13], p = 0.003). Patients without a nonfunctional allele de-escalated to clopidogrel had no difference in risk compared with those initiated and continued on prasugrel/ticagrelor (21 vs. 19 events/100 patient-years; adjusted HR 1.13 [0.51-2.34], p = 0.751).
CYP2C19-guided escalation and de-escalation is common in a real-world setting. Continuation of clopidogrel in nonfunctional allele carriers is associated with adverse outcomes. De-escalation to clopidogrel in patients without a nonfunctional allele appears safe and warrants prospective study.
评估经皮冠状动脉介入治疗（PCI）后实施 CYP2C19 基因分型后抗血小板治疗转换的频率及其对临床的影响。
对 1063 例行 CYP2C19 基因分型的 PCI 患者进行了抗血小板药物升级（氯吡格雷转换为普拉格雷/替格瑞洛）和降级（普拉格雷/替格瑞洛转换为氯吡格雷）的频率评估。评估了一年内心血管不良事件（MACCE）和出血事件的风险。
抗血小板治疗转换较为常见（19%），分别有 88%（101/115）和 92%（77/84）的患者在 CYP2C19 无功能等位基因和非无功能等位基因的情况下发生了升级和降级。无功能等位基因携带者起始并继续使用氯吡格雷，与升级为普拉格雷/替格瑞洛的患者相比，发生 MACCE 或出血事件的风险显著更高（52 与 19 事件/100 患者年；调整后的危险比 [HR] 2.89 [1.44-6.13]，p=0.003）。无功能等位基因的患者降级为氯吡格雷与起始并继续使用普拉格雷/替格瑞洛的患者相比，风险无差异（21 与 19 事件/100 患者年；调整后的 HR 1.13 [0.51-2.34]，p=0.751）。
CYP2C19 指导的升级和降级在真实世界中较为常见。无功能等位基因携带者继续使用氯吡格雷与不良结局相关。无功能等位基因的患者降级为氯吡格雷似乎是安全的，值得进一步前瞻性研究。
