不同剂量氯吡格雷联合阿司匹林在CYP2C19基因即时检测下对HR-NICE患者的疗效研究

Efficacy of Different Doses of Clopidogrel in Combination with Aspirin in Patients with HR-NICE by Point-of-care Testing of CYP2C19 Gene

目的探讨不同剂量氯吡格雷联合阿司匹林在即时检测(point-of-care testing,POCT)细胞色素P-4502C19(CYP2C19)基因型精准指导下治疗高危非致残性缺血性脑血管事件(high-risk non-disabling ischemic cerebrovascular events,HR-NICE)的疗效。方法采用单中心、随机、前瞻、盲法评估。在2021年3月~2022年1月于徐州市中心医院脑卒中绿色通道及神经内科病房连续纳入HR-NICE患者,刮取颊黏膜行POCT筛选CYP2C19功能缺失等位基因携带者,按照随机数字表法分为强化组(氯吡格雷150mg/d)和常规组(氯吡格雷75mg/d)均联合阿司匹林(100mg/d)双重抗血小板治疗21天。收集两组患者的一般基线资料、急性脑卒中Org 10172治疗试验(TOAST)分型及90天改良Rankin量表(mRS)评分、不良事件及严重不良事件发生等情况。主要疗效结局为90天内新发脑卒中,主要安全结局为90天内严重或中度出血。结果共筛查1301例HR-NICE患者,携带CYP2C19功能缺失等位基因727例,符合纳入标准的476例:强化组236例,常规组240例。两组患者基线比较,差异均无统计学意义(P>0.05);两组90天新发脑卒中强化组4例(1.7%),常规组26例(10.8%),两组比较差异有统计学意义(χ^(2)=16.827,P<0.001);两组90天中重度出血强化组0例,常规组1例(2.5%),两组比较差异无统计学意义(P>0.05)。结论对于CYP2C19功能缺失等位基因的HR-NICE患者,在抗血小板药物阿司匹林联合氯吡格雷的治疗中,强化氯吡格雷剂量的有效性优于常规剂量,且其安全性一致,未发生更多的出血等不良事件。

Objective To investigate the efficacy of different doses of clopidogrel combined with aspirin in the treatment of high-risk non-disabling ischaemic cerebrovascular events(HR-NICE)under the precise guidance of point-of-care testing(POCT)of cytochrome P-4502C19(CYP2C19)genotype.Methods The single-center,randomised,prospective,and blinded endpoint assessment was used.HR-NICE patients continuously enrolled in the stroke green channel and neurology ward of Xuzhou Central Hospital from January 2021 to January 2022,and all patients scraping of the buccal mucosa will be screened for CYP2C19 loss-of-function allele carriers by POCT.According to the random number table method,they were divided into the intensive group(clopidogrel 150mg/d)and the conventional group(clopidogrel 75mg/d)combined with aspirin(100mg/d)dual antiplatelet for 21 days.Baseline information,acute stroke Org 10172 treatment trial(TOAST)staging and 90 days modified Rankin scale(mRS)score and occurrence of adverse events and severe adverse events were collected for the two groups.The primary efficacy outcome was new stroke within 90 days and the primary safety outcome was severe or moderate bleeding within 90 days.Results A total of 1301 patients were screened,of which 727 patients carried CYP2C19 loss-of-function allele,and 476 patients were included:236 patients in the intensive group and 240 patients in the conventional group.The differences between the two groups were not statistically significant at baseline(P>0.05);4 cases(1.7%)in the intensive group and 26 cases(10.8%)in the conventional group had a new stroke at 90 days.The differences between the two groups were statistically significant(χ^(2)=16.827,P<0.001);0 case(0)in the intensive group and 1 case(2.5%)in the conventional group had moderate to severe haemorrhage at 90 days.The differences between the two groups was not statistically significant(P>0.05).Conclusion In HR-NICE patients with CYP2C19 loss-of-function allele,the enhanced clopidogrel dose was more effective than the conventional dose in the treatment with the antiplatelet drug aspirin combined with clopidogrel,and had a consistent safety profile with no more adverse events such as bleeding.