A Prospective Cohort Study On The Effect Of Early Intervention Program Combined With Disease And Syndrome On The Prognosis Of Acute Ischemic Strok

PurposeTo evaluate the clinical efficacy of early TCM interventional programme in short-term and long-term of acute ischemic stroke(AIS)patients,we conducted a multi-center prospective cohort study.We also explored the population which may be suitable for the early interventional programme.MethodsUtilizing a prospective cohort design,we included patients within 7 days of the stroke onset.The exposure was early TCM interventional programme for this study.According to patients’and their family members’ willing,they will decide whether to choose the early TCM interventional programme or not,thus generating the early interventional programme group and routine treatment group.Treatments in the early interventional programme group were based on the Guidelines for diagnosis and treatment of acute ischemic stroke in China 2014,plus Xingnaojing injection and the TCM granules based on syndrome differentiation.Xingnaojing was diluted with 250ml 0.9%sodium chloride,it was used every 12 hours and the course of treatment was 7 to 10 days.Huatan Tongluo granule is the main prescription of TCM granules.If the inner fire syndrome was diagnosed according to the ischemic stroke syndrome factor diagnostic scale,Xinglou Chengqi granule would be used in a short term for 1-3 days.If the diagnosis of qi deficiency syndrome was established,Yiqi Huayu granule would be used.The treatment course of TCM granules was 14 days.Patients in the routine treatment group received the standardized medical treatment only,according to the Guidelines for diagnosis and treatment of acute ischemic stroke in China 2014.For efficacy evaluation,we mainly focused on the long-term and short-term prognosis.The long-term prognosis was evaluated by the modified Rankin scale(mRS)and Bathel Index(BI)at 90th day of stroke onset.The short-term prognosis was evaluated by National Institutes of Health Stroke Scale(NIHSS)and Patientreported outcome(PRO).MRS and BI were dichotomous outcomes and the differences were compared between groups by χ2 test.The differences between NIHSS score and PRO score were compared by nonparametric test.Logistic regression was used to explore the relationship between syndromes and prognosis.This study was part of the clinical evaluation of the early interventional programme for ischemic stroke of the National Science and Technology Support Program of the 12th five-year plan.The protocol was approved by the Ethics Committee of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine before commencing the trial.The ethical review batch number of this study was ECPJ-BDY-2016-07.We registered the study on the website of Chinese Clinical Trial Rregistry prior to the study and the registration number was ChiCTROPC-16008451.ResultsFrom May 2016 to February 2018,809 paticipants were enrolled in our study from 24 centers across China,487 in the early interventional programme group and 322 in the routine treatment group.Participants within 7 days of the onset of ischemic stroke were recruited consecutively in each center.Long-term prognosis:The proportions of patients with a favorable 3-month functional recovery were 69%vs 67.5%for the early interventional programme group and routine treatment group respectively.The propotion of patients with good activities of daily life was 66.8%for the early interventional programme group and 64.3%for the routine treatment group.The proportions of patients with good outcomes in the early interventional programme group were higher than those in the routine treatment group.We then compared the proportions of patients with good functional outcome(mRS≤1)and good activities of daily life(BI≥90)between groups,there was no statistically significant difference(P>0.05).Short-term prognosis:After treatment,there was no statistically significant difference between the two groups for the NIHSS score.For the four dimensions of PRO scale,the comparison was statistically significant for the dimension of treatment satisfaction between the two groups(P<0.05),patients in the early interventional programme group were more satisfied with their treatment than patients in the routine treatment group.We divided the participants into two subgroups with a NIHSS score of 7,that is the relatively heavy group(NIHSS score of 7 or more,N=203)and the relatively mild group(NIHSS<7,N=606).It was found that in the relatively heavy subgroup,patients in the early interventional programme improved better and the difference of NIHSS score between baseline and 14th day was statistically significant(P<0.05).In the relatively mild subgroup,we didn’t find a significant statistical difference in prognosis between groups.In our study,83.7%of the participantsin were enrolled in 96 hours.In the relatively heavy group,we further diveided the patients into two subgroups,that is,if patients were enrolled in 96 hours they were assigned to the early group(N=165),otherwise they they would be assigned to the late group(N=38).We found that patients in the early group with the interventional programme improved better,that is,the difference of NIHSS scores between baseline and the 7th day,and the difference between baseline and the 14th day were statistically significant(P<0.05).In the late group,there was no significant statistical difference in prognosis between groups.Logistic regression was used to explore the relationship between syndromes and prognosis of acute ischemic stroke.It was found that internal wind syndrome,phlegm dampness syndrome and blood stasis syndrome were the key syndromes related to the prognosis of acute ischemic stroke.Conclusions1.From the results of the whole study,there was a trend that early TCM interventional programme can improve the prognosis of AIS patients in short-term and long-term.2.The results of subgroup analysis showed that early TCM interventional programme may be more suitble for those AIS patients with relatively more severe neurologic deficits and received the early TCM interventional programme earlier.3.Patients with early TCM interventional programme were more satisfied with their treatment compared to those underwent routine treatment.4.Internal wind syndrome,phlegm dampness syndrome and blood stasis syndrome are related to the prognosis of ischemic stroke.The main methods of treating acute ischemic stroke are to extinguish the wind,reduce phlegm,and activate the blood circulation.