Clinical Efficacy Of Clopidogrel In Treatment Of The Symptomatic Cerebral Artery Stenosis Subjects With CYP2C19 Intermediate Metabolizers Genotype

ObjectiveTo evaluate clinical efficacy of standard and double dose of clopidogrel in symptomatic(moderate to severe)cerebral artery stenosis subjects with CYP2C19intermediate metabolizers genotype(IM)within 3 months.MethodAcute cerebral infarction patients admitted to Yantai Yuhuangding Hospital Affiliated to Qingdao University from June 2018 to December 2018 were enrolled successively.Patients all finished brain MRI and intracranial MRA,bilateral carotid and vertebral artery color Doppler ultrasonography and CYP2C19 gene detection.A total of 149 cerebral infar tion patients certified moderate to severe cerebral artery stenosis by MRI/MRA who carried~*2 or~*3 heterozygosity of CYP2C19 gene(CYP2C19 IM)were randomized into a standard clopidogrel dose group(aspirin 100 mg/d,clopidogrel 75 mg/d)×21 d and a double clopidogrel dose group(aspirin 100 mg/d,clopidogrel 150 mg/d)x21d.Basic characterics as gender,age and history of hypertension,Dibetes melitus,stroke,alcohol consumption,smoking and laboratory investigations,imaging examinations were collected.NIHSS and mRS scores when patients were admitted to and discharged from hospital were recorded.Patient’s mRS scores followed up by telephone or readmission records within 3months.Clinical events as TIA(transient ischemic attack),cerebral infarction,coronary atherosclerotic heart disease and cerebral hemorrhage,gastrointestinal bleeding,skin/mucous membrane ecchymoses or hemorrhage and death were recorded within 3months.ResultA total of 149 patients were enrolled,including 76 in the standard group and 73 in the double dose group.1.There was no significant difference betweent the two groups of basic characterics,past and personal history,vital signs at admission and laboratory investigative results.2.Seven of 76 patients experienced vascular events,two of the 7 patients died of recurrent cerebral infarction in standard group.Only 1 of 73 patients readmitted withrecurrent cerebral infarction in double dose group.The double dose group has a trend of lower reccurence of ischemic vascular events within 3 months(P=0.063).3.There was no significant difference in neurological function scores(mRS≤2 points)between two groups within 3 months(P>0.05).4.Considered common variables related to vascular events(gender,age,systolic blood pressure,total cholesterol,NIHSS),multivariate COX regression analysis revealed that double dose clopidogrel regimen was associated with decreased occurrence of vascular events(P=0.046).5.When the patients used the drug for one month and three months,one patient occurred skin and mucosal ecchymosis.Conclusion1.Double dose of clopidogrel regimen(150 mg/d x21d)can reduce the occurrence of ischemic cerebrovascular events in the symptomatic cerebral artery stenosis subjects with CYP2C19 IM genotype within 3 months.2.Double maintenance dose of clopidogrel is not associated with recovery of stroke neurological function.3.There were no serious bleeding events occurred during and after treated by clopidogrel and aspirin in two groups within 3 months.In summary:The symptomatic cerebral artery stenosis subjects with CYP2C19 IM genotype treated by double dose of clopidogrel has a trend of reduced ischemic vascular events within 3 months.