不同抗血小板治疗方案在CYP2C19~*2等位基因型缺陷患者PCI术后疗效及安全性的比较

Comparison of efficacy and safety of different antiplatelet therapy in patients with CYP2C19~*2 genotype deficiency after PCI

目的比较不同抗血小板治疗方案在CYP2C19~*2基因型缺陷患者经皮冠状动脉介入治疗(PCI)术后疗效及安全性。方法纳入2014年6月～2016年12月于河北省人民医院心内科住院行PCI术冠心病患者458例,PCI术后常规应用阿司匹林(100 mg)+氯吡格雷(75 mg)治疗,采用Taqman-realtime PCR法监测CYP2C19~*2基因型,筛选出CYP2C19基因~*2基因型缺陷212例,采用随机数字表法分为4组:标准抗血小板组(C组:n=46,阿司匹林100 mg+氯吡格雷75 mg,1/d);氯吡格雷双倍剂量组(D组:n=50,阿司匹林100 mg 1/d+氯吡格雷150 mg,1/d(1月后减量为75 mg,1d);氯吡格雷联用通心络组(L组:n=59,阿司匹林100 mg+氯吡格雷75 mg,1/d+通心络0.26 g/粒,4粒×3/d);替格瑞洛组(n=57,T组:90 mg,2/d+阿司匹林100 mg,1/d),分别于PCI术后3 d、1个月、3个月时随访,用TEG血栓弹力图仪检测血小板的抑制率,记录患者PCI术后3个月内不良心血管事件和出血事件的发生情况。结果 (1)术后1个月,与C组比较,D组、L组和T组血小板抑制率均增高,且T组>D组>L组,差异具有统计学意义(P<0.05)。术后3个月时,与C组比较,L组和T组的血小板抑制率增高,D组血小板抑制率降低,差异有统计学意义(P<0.05);与L组比较,T组的血小板抑制率增高(P<0.05);(2)与C组比较,D组、L组及T组患者总不良心血管事件发生率降低(P<0.05),四组患者单一不良心血管事件发生情况差异无统计学意义(P>0.05);(3)出血情况,四组患者均为轻度出血。与C组比较,T组出血发生率高(P<0.05),L组、D组差异无统计学意义(P>0.05)。结论 (1)CYP2C19~*2基因型氯吡格雷低反应患者PCI术后采用不同抗血小板治疗替格瑞洛疗效优于标准抗血小板治疗、氯吡格雷双倍剂量及氯吡格雷联用通心络,但其出血风险增加,但为轻度出血。(2)标准抗血小板治疗方案较其他方案更容易出现心血管不良事件。

Objective To compare the efficacy and safety of different antiplatelet therapy in patients with CYP2C19*2 genotype deficiency after PCI.Methods From June 2014 to December 2016,458 coronary artery disease patients in the Hebei General Hospital were enrolled in this study.The patients took aspirin(100 mg)and Clopidogrel(75 mg)a day routinely after PCI.Using TaqMan Realtime PCR method to detect the polymorphisms of CYP2C19*2 gene in selected patients.The patients were divided into four groups:(1)regular dose of Clopidogrel group(group C:n=46,aspirin 100 mg+clopidogrel 75 mg,qd);(2)double dose of Clopidogrel group(group D:n=50,aspirin 100 mg,qd+clopidogrel 150 mg,qd,decrease to 75 mg,qd after 1 month);(3)Tongxinluo capsule combined with regular antiplatelet therapy group(group L:n=59,aspirin 100 mg qd+clopidogre75 mg qd+tongxinluo 4 pills,tid);(4)Ticagrelor group(group T:n=57,90mg,bid+aspirin100 mg,qd).Followed up at 3 days,1 month and 3 months after PCI.Additionally,TEG was applied to detect the level of platelet inhibition rate.The Major Adverse Cardiac events(MACE)and bleeding events were observed after PCI in 3 month.The PAG and the incidence of MACE within 1 year among four groups was compared.Results After 1 month follow-up,the platelet inhibition rates were increased in group T,group D and group L(Group T>Group D>Group L,P<0.05).After 3 months of follow-up,the platelet inhibition rates were increased in group T and group L(group T>group L,P<0.05),but it was deceased in group D(P<0.05).Compared with group C,the incidences of total adverse cardiovascular events in group D,group L and group T were decreased(P<0.05).There was no significant difference of the incidence of single adverse cardiovascular events among four groups(P>0.05).Mild bleeding was founded in all groups.Compared with group C,the incidence of bleeding in T group was higher(P<0.05).There is no difference between group L and group D(P>0.05).Conclusions For patients with CYP2C19*2 genotype deficiency,the efficacy of ticagrelor after PCI is better than regular dose of Clopidogrel,double dose of Clopidogrel and Tongxinluo capsule combined with antiplatelet.The risk of bleeding is increased(mild bleeding).