精准医疗在经皮冠状动脉介入术后抗血小板药物选择中的作用

目的:探讨精准医疗、个体化给药在经皮冠状动脉介入术(PCI)后抗血小板药物选择中的作用。方法:入选PCI后服用常规剂量阿司匹林(100 mg/d)和氯吡格雷(75 mg/d)且疗程在3个月左右的患者,根据CYP2C19基因多态性检测结果,将患者分为快代谢组、中代谢组和低代谢组,并给予个体化干预治疗。快代谢组继续服用常规剂量的阿司匹林和氯吡格雷;中代谢组将氯吡格雷调整为1.5倍剂量;低代谢组分为两组,氯吡格雷组将氯吡格雷调整为2倍剂量,替格瑞洛组将氯吡格雷改换为替格瑞洛(90 mg、2次/d)。检测各组个体化干预治疗前后凝血指标和血小板聚集率的变化及干预治疗后的出血事件。结果:各组患者干预治疗前后组间和组内比较,凝血指标差异均无统计学意义(P均0.05)。干预治疗前,血小板聚集率为快代谢组中代谢组低代谢组,3组间差异均有统计学意义(P均0.05);干预治疗后,中代谢组患者血小板聚集率较干预治疗前明显下降(P0.05),低代谢组中氯吡格雷组血小板聚集率与干预治疗前比较差异无统计学意义,替格瑞洛组血小板聚集率较干预治疗前明显下降(P0.05)。干预治疗后快代谢组、中代谢组血小板聚集率差异无统计学意义;低代谢组中替格瑞洛组血小板聚集率明显低于快/中代谢组,氯吡格雷组仍明显高于快/中代谢组(P均0.05)。干预治疗后,中代谢组、低代谢组与快代谢组比较出血风险均未增加(P均0.05)。结论:根据CYP2C19基因多态性检测结果个体化给药,可提高抗血小板治疗效果,且不增加出血风险。对于CYP2C19基因型为低代谢型的患者建议改用替格瑞洛治疗。

The role of precision medicine in antiplatelet drug selection after percutaneous coronary intervention

Objective:To investigate the role of precision medical and individualized administration of antiplatelet drugs after percutaneous coronary intervention (PCI).Methods:Patients treated with routine dose of aspirin (100 mg/d) and clopidogrel (75 mg/d) after PCI were selected for a course of treatment for about 3 months.According to the CYP2C19 gene polymorphism test,the patients were divided into fast metabolic group,middle metabolic group and low metabolic group,and then treated with individual intervention.The fast metabolic group continued to take conventional doses of aspirin and clopidogrel,and the middle metabolic group changed clopidogrel dose to 1.5 times.The low metabolic group was divided into clopidogrel group and ticagrelor group.Patients in the clopidogrel group received 2 times the dose of clopidogrel,while patients in the ticagrelor group were treated with ticagrelor 90 mg (2 times/d) for replacement of clopidogrel.The changes of coagulation indexes and platelet aggregation rate before and after individual intervention and the bleeding events after intervention were counted.Results:There was no statistically significant difference in blood coagulation indexes between the groups before and after intervention (all P＞0.05).Before the intervention,the platelet aggregation rate showed fast metabolic group ＜ middle metabolic group ＜ low metabolic group,and the differences among the three groups were statistically significant (all P＜0.05).After intervention,the platelet aggregation rate of middle metabolic group was significantly increased (P ＜ 0.05).Platelet aggregation rate of low metabolic clopidogrel group had no statistical difference while the platelet aggregation rate of ticagrelor group was significantly decreased compared with those before intervention (both P ＜ 0.05).After intervention,the fast and the middle metabolic groups had no significant difference between the platelet aggregation rate.The platelet aggregation rate in the low metabolic ticagrelor group was significantly lower while the low metabolic clopidogrel group was higher than the fast and the middle metabolic groups (all P＜0.05).The risk of bleeding was not increased in the low or middle metabolic group compared with the fast metabolic group after intervention (P＜0.05).Conclusions:According to the results of CYP2C19 gene polymorphism test,individualized administration can improve antiplatelet therapy without increasing the risk of bleeding.For CYP2C19 low metabolic genotype,ticagrelor is recommended.