Preventive Effects Of Naoxintong Capsules On Recurrence Of Ischemic Stroke In Patients With Qi Deficiency And Blood Stasis Constitution And The CYP2C19~*2,~*3 Gene Mutation

Objective:The purpose of this study was to determine the impact of the adjunctive, Buchang Naoxintong Jiaonang (BNJ) to Clopidogrel on the ischemic stroke and transient cerebral ischemic attacks (TIA) with Qi Deficiency and Blood Stasis Constitution and the CYP2C19*2,*3 Gene Mutation, including platelet aggregation and the short-term prevention of recurrent ischemic events effect. We will try to solve the issue of the high rate of ischemic stroke and propose new ideas with individualized treatment.Methods:This study was a single-center prospective design, including ischemic Stroke/TIA patients with Qi Deficiency and Blood Stasis Constitution and the CYP2C19*2,*3 Gene Mutation, admitted in Fujian Provincial Hospital Department of Neurology during 2012-2014. The patients were randomly divided into Naoxintong group and Control group. The patients of the Control group were given Clopidogrel 75mg/d and other conventional treatment whereas those of the Naoxintong group were given four Naoxintong Capsules additionally three times a day until the end of follow-up.Platelet aggregation was tested before treatment and post-treatment after seven days. Thromboela-stogram was performed after seven days’treatment. The primary endpoint is defined as recurrent ischemic stroke. Treatment and follow-up 180 days course analyzed the associated risk factors.The total case of ischemic Stroke/TIA patients group carrying CYP2C19 gene of poor metabolism and intermediary metabolism were 83 cases, with the average age of patients being 65.94±10.26 years old and including 61 male and 22 female. Among the Naoxintong group, there were 41 patients and Control group had 42. Comparing the Baseline data, including gender, age,type of cerebral infarction, CYP2C19 genotype,history of hypertension, diabetes, coronary heart disease, ischemic Stroke/TIA history, smoking history,alcohol history, hs-CRP, HCY, FPG, HbAlc, PLT, ALT, AST, HDL, TG, UA, BMI, NIHSS score, MRS score, ESSEN score and so on, the differences were not statistically significant (P>0.05). LDL median value in Naoxintong group is higher than Control group.There was a statistically significant difference between them(P=0.023).Result:1,Platelet activity detection:(1)Platelet aggregation:Before treatment, the difference of platelet aggregation between the two groups had no statistical significance (P=0.371), but there was an obvious decrease after treatment. There was significant difference among them(P<0.000,0.001);After treatment, the platelet aggregation of Naoxintong group was significantly lower than the control group. The difference among the two groups was statistically significant (P=0.002).(2)Thromboela-stogram:TEG was measured after 7 days treatment. The median value of MA in Naoxintong group is lower than Control group. There was statistically significant difference among them(P<0.001). ADP inhibition rate in Naoxintong group was higher than that in the Control group so that the difference was statistically significant between them(P<0.001).2, Recurrence of ischemic stroke and risk factors:At the end of follow-up 180d, including 1 patient was lost and endpoint events occurred to 14 patients. In Naoxintong group there were 3 patients, in which one patient died and in the Control group, endpoint events occurred, among which 1 patient died and the remaining 10 cases occurred ischemic stroke/TIA again. The occurrence of endpoint events in Naoxintong group (7.32%) was lower than that in control group (26.19%). The difference was significant (X2=5.270,P=0.022). These two groups did not have bleeding events or adverse drug reactions.The univariate analysis of baseline data compared in two groups with recurrent an d non-recurrent patients, showed that age, Naoxintong treatment intervention,history of diabetes, BMI, ESSEN score had a statically significant difference (P<0.05).Combined with the clinical experience and the results of the univariate analysis,the drug treatme-nt interventions (Naoxintong group VS control group), BMI (overweight VS normal), ESSEN score (high-risk VS low risk),LDL (≥1.8mmol/1 VS<1.8mmol/1)were includedin the multivariate analysis.The results showed that,BMI(HR,4.706;95%CI:1.644-13.470;P =0.004), ESSEN score (HR,4.814;95%CI:1.342-17.273;P=0.016) were risk factors of is chemic stroke recurrence,and Naoxintong treatment (HR,0.232;95%CI:0.081-0.667;P=0.0 07) was an independent protective factor.In conclusion:1.ESSEN score,as high-risk, BMI as overweight were risk factors of ischemic stroke/TIA recurrence with CYP2C19*2,*3 gene mutation.2.Naoxintong Capsules can reduce the short-term risk of recurrence of ischemic Stroke /TLA patients carrying CYP2C19*2,*3 gene. The mechanism may be associated with the reduction of platelet aggregation activity.