Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, China.
Department of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
J Cardiovasc Pharmacol. 2024 Sep 1;84(3):347-355. doi: 10.1097/FJC.0000000000001582.
Guidelines on antiplatelet recommendation for CYP2C19 intermediate metabolizer (IM) have not come to an agreement. This study aimed to evaluate the clinical benefit of ticagrelor when compared with high-dose clopidogrel in CYP2C19 IM after percutaneous coronary intervention for acute coronary syndromes. Patients were enrolled according to CYP2C19 genotype and individual antiplatelet therapy. Patient characteristics and clinical outcomes were collected through electronic medical record system. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE), namely a composite of death from cardiovascular causes, myocardial infarction, stroke, and stent thrombosis within 12 months. The secondary outcome was Bleeding Academic Research Consortium scale bleeding events within 12 months. The Cox proportional hazards regression model was performed, with inverse probability treatment weighting (IPTW) adjusting for potential confounders. A total of 532 CYP2C19 IM were enrolled in this retrospective single-center study. No statistically significant difference in incidence rate of MACCE was found between patients receiving ticagrelor versus clopidogrel (7.01 vs. 9.52 per 100 patient-years; IPTW-adjusted hazard ratio 0.71; 95% confidence interval: 0.32-1.58; adjusted log-rank P = 0.396), but the incidence rate of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding events was statistically higher in the loss of function-ticagrelor group than in the loss of function-clopidogrel group (13.53 vs. 6.16 per 100 patient-years; IPTW-adjusted hazard ratio: 2.29; 95% confidence interval: 1.10-4.78; adjusted log-rank P = 0.027). Ticagrelor treatment in CYP2C19 IM resulted in a statistically higher risk of bleeding compared with high-dose clopidogrel, whereas a clear association between treatments and MACCE warrants further investigations.
关于细胞色素 P450 2C19(CYP2C19)中间代谢型(IM)患者的抗血小板推荐指南尚未达成共识。本研究旨在评估替格瑞洛与高剂量氯吡格雷相比,在 CYP2C19 IM 经皮冠状动脉介入治疗(PCI)治疗急性冠脉综合征(ACS)后的临床获益。根据 CYP2C19 基因型和个体抗血小板治疗对患者进行入组。通过电子病历系统收集患者特征和临床结局。主要结局是主要不良心脑血管事件(MACCE),即 12 个月内心血管死亡、心肌梗死、卒中和支架血栓形成的复合终点。次要结局是 12 个月内 Bleeding Academic Research Consortium(BARC)出血事件。采用 Cox 比例风险回归模型,采用逆概率治疗加权(IPTW)校正潜在混杂因素。这项回顾性单中心研究共纳入 532 例 CYP2C19 IM 患者。接受替格瑞洛与氯吡格雷治疗的患者 MACCE 发生率无统计学差异(替格瑞洛组为 7.01/100 患者年,氯吡格雷组为 9.52/100 患者年;经 IPTW 校正的风险比为 0.71;95%置信区间:0.32-1.58;校正后的 log-rank P=0.396),但替格瑞洛组功能性失活(loss of function,LOF)-替格瑞洛组的 BARC 2、3 或 5 级出血事件发生率明显高于氯吡格雷组(替格瑞洛组为 13.53/100 患者年,氯吡格雷组为 6.16/100 患者年;经 IPTW 校正的风险比为 2.29;95%置信区间:1.10-4.78;校正后的 log-rank P=0.027)。与高剂量氯吡格雷相比,CYP2C19 IM 患者使用替格瑞洛治疗可显著增加出血风险,而治疗与 MACCE 之间的明确关联需要进一步研究。