Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People's Republic of China.
Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People's Republic of China.
Eur J Clin Pharmacol. 2023 Sep;79(9):1249-1259. doi: 10.1007/s00228-023-03519-y. Epub 2023 Jul 14.
We aimed to explore the contribution of genotype-guided selection of P2Y inhibitors on prognosis in Chinese patients with acute coronary syndromes (ACS) or chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI).
Totally, 2063 patients were included. They were divided into empiric treatment group (n = 1025) and individualized treatment group (n = 1038) depending on whether taken CYP2C19 genetic testing. The incidences of clinical endpoint events were compared in two groups at 1-year follow-up. The effective endpoint events were major adverse cardiovascular events (MACEs), including all-cause mortality, in-stent restenosis, nonfatal myocardial infarction, nonfatal stroke and severe recurrent ischemia. Meanwhile, the safe endpoint was bleeding events defined by the Bleeding Academic Research Consortium (BARC) criteria.
Finally, 66.83% patients were diagnosed with ACS and 33.17% patients were diagnosed with CCS in empiric group. 68.11% patients were diagnosed with ACS and 31.89% patients were diagnosed with CCS in individualized group. At 1-year follow-up, individualized group showed lower MACEs rate than empiric group (19.61% vs. 10.69%, HR: 1.915; 95% CI: 1.534 to 2.392; P < 0.0001, log-rank test; adjusted HR: 1.983; 95% CI: 1.573 to 2.501; P = 0.000, cox proportional hazards regression models), while bleeding events were significantly less common in empiric group than in individualized group (7.32% vs. 10.40%, HR: 0.693; 95% CI: 0.519 to 0.926; P = 0.0132, log-rank test; adjusted HR: 0.695; 95% CI: 0.518 to 0.933; P = 0.016, cox proportional hazards regression models). It was mainly manifested in BARC class 1 bleeding, which did not warrant the interruption of antiplatelet therapy (ITA). Further, subgroup analyses illustrated that no significant difference existed in cumulative MACEs-free survival rate between all treatment arms of individualized group (P = 0.6579 by log-rank test), and CYP2C19 intermediate metabolizer (IM) genetype appeared to be significantly associated with bleeding events for patients treated with ticagrelor (clopidogrel vs. ticagrelor: 6.80% vs. 14.88%; adjusted HR:0.440; 95% CI: 0.246 to 0.787; adjusted P = 0.006).
Genotype-guided selection of P2Y inhibitor made a very positive contribution on the prognosis in Chinese ACS/CCS patients undergoing PCI. Instead of intensifying antiplatelet strategies, conventional-dose clopidogrel could be recommended as P2Y inhibitor after weighing MACEs and bleeding events in CYP2C19 IM patients.
我们旨在探讨在接受经皮冠状动脉介入治疗（PCI）的中国急性冠状动脉综合征（ACS）或慢性冠状动脉综合征（CCS）患者中，基于基因型的 P2Y 抑制剂选择对预后的影响。
共纳入 2063 例患者。根据是否进行 CYP2C19 基因检测，将患者分为经验治疗组（n=1025）和个体化治疗组（n=1038）。在 1 年随访时比较两组的临床终点事件发生率。有效终点事件为主要不良心血管事件（MACEs），包括全因死亡率、支架内再狭窄、非致死性心肌梗死、非致死性卒中和严重复发性缺血。同时，出血事件的安全终点定义为 Bleeding Academic Research Consortium（BARC）标准。
经验组中，66.83%的患者被诊断为 ACS，33.17%的患者被诊断为 CCS；个体化组中，68.11%的患者被诊断为 ACS，31.89%的患者被诊断为 CCS。在 1 年随访时，个体化组的 MACEs 发生率低于经验组（19.61% vs. 10.69%，HR：1.915；95%CI：1.534 至 2.392；P<0.0001，log-rank 检验；调整 HR：1.983；95%CI：1.573 至 2.501；P=0.000，Cox 比例风险回归模型），而经验组的出血事件发生率明显低于个体化组（7.32% vs. 10.40%，HR：0.693；95%CI：0.519 至 0.926；P=0.0132，log-rank 检验；调整 HR：0.695；95%CI：0.518 至 0.933；P=0.016，Cox 比例风险回归模型）。主要表现为 BARC 1 级出血，无需中断抗血小板治疗（ITA）。进一步的亚组分析表明，个体化组中所有治疗组的累积 MACE 无事件生存率无显著差异（log-rank 检验 P=0.6579），CYP2C19 中间代谢者（IM）基因型与接受替格瑞洛治疗的患者的出血事件显著相关（氯吡格雷 vs. 替格瑞洛：6.80% vs. 14.88%；调整 HR：0.440；95%CI：0.246 至 0.787；调整 P=0.006）。
在接受 PCI 的中国 ACS/CCS 患者中，基于基因型的 P2Y 抑制剂选择对预后有非常积极的影响。在 CYP2C19 IM 患者中，权衡 MACE 和出血事件后，可推荐常规剂量氯吡格雷作为 P2Y 抑制剂，而不是强化抗血小板策略。
