氯吡格雷精准用药对缺血性脑卒中脑动脉重建术后疗效的影响

Effect analysis of precision dosing of clopidogrel on the efficacy after cerebral artery reconstruction in ischemic stroke

目的分析氯吡格雷精准用药对缺血性脑卒中脑动脉重建术后疗效的影响。方法回顾性分析255例行脑动脉重建术的缺血性脑卒中患者的临床资料,研究期间失访12例,最终纳入243例。将患者根据是否进行CYP2C19基因多态性检测指导氯吡格雷抗血小板治疗分为研究组(87例,精准用药)和对照组(156例,常规用药)。采用倾向性评分匹配(PSM)方法控制两组的混杂因素,通过PSM成功匹配77对,研究组和对照组各77例。分析研究组PSM后CYP2C19基因型分布;比较两组PSM前后的临床资料,两组PSM后的疗效及安全性。结果PSM后,研究组中CYP2C19正常代谢型和中间代谢型占比一致,均为42.9%(33/77),慢代谢型占比为14.3%(11/77),快代谢型占比为0。CYP2C19*2和CYP2C19*3携带率为57.1%(44/77),CYP2C19*17携带率为1.3%(1/77)。PSM前,研究组女性占比为18.4%,高于对照组的9.6%,差异具有统计学意义(P<0.05);两组年龄、民族、糖尿病史、高血压病史、脑卒中病史、吸烟史、饮酒史、基线美国国立卫生研究院卒中量表(NIHSS)评分、责任血管、取栓情况、入院低密度脂蛋白胆固醇(LDL-C)、体质量指数(BMI)、发热情况比较差异无统计学意义(P>0.05)。PSM后,两组年龄、性别、民族、糖尿病史、高血压病史、脑卒中病史、吸烟史、饮酒史、基线NIHSS评分、责任血管、取栓情况、入院LDL-C、BMI、发热情况比较差异均无统计学意义(P>0.05)。术后随访6个月,研究组患者复发率为3.9%,低于对照组的15.6%,差异具有统计学意义(P<0.05);研究组患者预后结局良好率、出血事件发生率、全因死亡率均略低于对照组,但差异无统计学意义(P>0.05)。结论通过进行CYP2C19基因多态性检测指导氯吡格雷精准用药,虽对缺血性脑卒中患者脑动脉重建术后短期预后结局无显著影响,但可有效降低患者术后缺血性脑卒中复发风险,且不增加出血及死亡风险。

Objective To analyze the effect of precision dosing of clopidogrel on the efficacy after cerebral artery reconstruction in ischemic stroke.Methods The clinical data of 255 patients with ischemic stroke who underwent cerebral artery reconstruction were retrospectively analyzed,12 cases were lost to follow-up during the study period,and 243 cases were finally included.Patients were divided into a study group(87 patients,precision dosing)and a control group(156 patients,conventional dosing)based on whether or not CYP2C19 gene polymorphism testing was performed to guide clopidogrel antiplatelet therapy.The propensity score matching(PSM)method was used to control for confounding factors in both groups,and 77 pairs were successfully matched by PSM,with 77 cases each in the research group and control group.The distribution of CYP2C19 genotype after PSM in the research group was analyzed;the clinical data before and after PSM,as well as the efficacy and safety after PSM in the two groups were compared.Results After PSM,the proportion of CYP2C19 normal metabolite and intermediate metabolite in the research group was consistent,both at 42.9%(33/77),slow metabolite at 14.3%(11/77)and fast metabolite at 0.The carriage rate of CYP2C19*2 and CYP2C19*3 was 57.1%(44/77),and the carriage rate of CYP2C19*17 was 1.3%(1/77).Before PSM,the percentage of females in the research group was 18.4%,which was higher than 9.6%in the control group,and the difference was statistically significant(P<0.05).There was no statistically significant difference between the two groups in terms of age,ethnicity,history of diabetes mellitus,history of hypertension,history of stroke,history of smoking,history of alcohol consumption,baseline National Institutes of Health Stroke Scale(NIHSS)score,responsible vessel,embolism removal,admission low-density lipoprotein cholesterol(LDL-C),body mass index(BMI),and fever(P>0.05).After PSM,there were no statistically significant differences in terms of age,gender,ethnicity,history of diabetes mellitus,history of hypertension,history of stroke,history of smoking,history of alcohol consumption,baseline NIHSS score,responsible vessel,embolism removal,admission LDL-C,BMI,and fever between the two groups(P>0.05).At 6-month postoperative follow-up,the recurrence rate in the research group was 3.9%,which was lower than 15.6%in the control group,and the difference was statistically significant(P<0.05).The rate of good prognosis,incidence of bleeding events,and all-cause mortality in the research group were slightly lower than those in the control group,but the differences were not statistically significant(P>0.05).Conclusion The CYP2C19 gene polymorphism test for precision dosing of clopidogrel has no significant effect on the short-term prognostic outcome of patients with ischemic stroke after cerebral artery reconstruction,but it is effective in reducing the risk of recurrence of ischemic stroke without increasing the risk of bleeding or death.