The Efficacy And Safety Of Urokinase Intravenous Thrombolytic Therapy For Minor Stroke

Background:Stroke is a leading cause of death and disability in the world.Minor stroke,a subtype of stroke,accounts for about two-thirds of stroke approximately.By the comprehensive examination and appropriate treatment,the prognosis of minor stroke would be ameliorated and the disability and mortality would be attenuated.A large number of studies has shown that intravenous thrombolysis by rtPA is an effective and safe therapy for minor stroke patients.However,the cost of rtPA is too expensive to afford for many poor patients.At this time,urokinase,another drug for intravenous thrombolysis becomes their choice because of its cheap price.In fact,urokinase is being widely used in poor areas of our country as a substitute for poor stroke patients.However,the use of urokinase is lack of clinical study,and the efficacy and safety of it remains unclear.Therefore,it is of high significance to explore the efficacy and safety of urokinase treatment for acute minor stroke patients.Objective:To compare the efficacy and safety of urokinase thrombolytic therapy for minor stroke patients in different dosage and treatment time windows.Methods:(1)Acute ischemic stroke patients underwent urokinase thrombolysis were collected in 22 hospitals at Chongqing(include Yongchuan district,Qijiang count area,Yuzhong district,etc 17 hospitals.)and Sichuan Province(Hejiang city,dazhu county,Yibin city,etc 5 hospitals.)from January 2014 to January 2018.Minor stroke was defined as the baseline NIHSS score is less than 5.A total number of 126 minor stroke patients was included into the study.According to different time window,they were divided into less than 3 hours group,3-4.5 hours group,and 4.5-6 hours group.Furthermore,according to the urokinase dosages,they were divided into ? 1,000,000 units of urokinase;> 1,000,000 units of urokinase.(2)SAS9.2 was used for data analysis.The count data was expressed as rate.The comparison among the groups was conducted by chi-square test,fisher's exact test,cochran-armitage trend test,mann-whitney U test and kruskal-wallis test to conduct the Bonferroni correction by further compare.The metering data of skewed distribution was described as median and quartile spacing.The comparison among the groups was conducted by the mann-whitney U test and kruskal-wallis.The non-normal distribution measurement data of the paired design adopted the symbol to rank sum test.The multivariate logistic regression analysis model was used to analyze the variables of P < 0.05 in the logistic regression analysis,and the risk factors of the patient's prognosis in 3 months were analyzed by using dichotomous logistic regression analysis.The test level is 0.05.Results:(1)The efficacy of urokinase intravenous thrombolysis in the treatment of minor stroke: Compared the NIHSS score before thrombolysis treatment with the NIHSS score after 24 hours of thrombolysis treatment,the NIHSS score after 24 hours of thrombolysis treatment decreased by 1 points,which has statistical significance(P<0.05).In all minor stroke patients,the NIHSS scores of 88 cases(88/126,69.8%)decreased at 24 hours.The MRS scores of 105 cases(105/126,83.3%)were 0 or 1 at 3 months,while the MRS scores of other 21cases(21/126,16.7%)were more than 1.(2)The complication of urokinase intravenous thrombolysis in the treatment of minor stroke :2 cases(2/126,1.6%)had asymptomatic hemorrhaging.Their NIHSS scores decreased at 24 hours and their prognosis were good at 3 months.1 case(1/126,0.7%)had life-threatening symptomatic cerebral hemorrhage who died at 3 months.12 cases(12/126,9.5%)have oral mucosal hemorrhage,a minor complications.The cause of death at 3 months were as follows respectively: 1 case(1/126,0.79%)had symptomatic intracranial hemorrhage,1 case(1/126,0.79%)had cardiac insufficiency,1 case(1/126,0.79%)had vascular occlusion caused by large area cerebral infarction,1 case(1/126,0.79%)died of other causes.(3)The efficacy and safety in different thrombolysis time window were as follows: The number of patients of three thrombolysis time window treatment group(0-3 h,3-4.5 h and 4.5-6 h group)who has good functional outcome(MRS score is 0 or 1 at 3 months)were as follows respectively: 33 cases(33/43,76.74%),35 cases(35/42,83.33%)and 37 cases(37/41,90.24%),while there is no significance among them(P > 0.05).The complication rate of asymptomatic cerebral hemorrhage and symptomatic cerebral hemorrhage of the different time window patients were all low with no significance in comparison.Other bleeding site were skin,oral mucosal bleeding primarily and the bleeding rate among the groups were also not statistically significant(P > 0.05).(4)The efficacy and safety in different doses of urokinase were as follows: Both doses had good functional outcome(MRS score is 0 or 1 at 3 months)and there is no significance between them(P > 0.05).18.42% patients in high dose group(> 1,000,000 units)were observed to has skin and oral mucosal bleeding,while only 5.68% patients in low dose group(? 1,000,000 units)has that(P<0.05).The incidence of asymptomatic intracerebral hemorrhage and symptomatic intracerebral hemorrhage in two doses group were both low with no statistical significance(P>0.05).Conclusions:(1)For thrombolysis of minor stroke,it is effective and safe to use urokinase within 6 hours of disease onset.(2)Both the high(> 1,000,000 units)and low dose(? 1,000,000 units)of urokinase would have a good prognosis,while the low dose has a low bleeding risk.We should be care of bleeding when using high dose urokinase.