阿替普酶改善缺血性脑卒中患者神经功能的有效性和安全性研究

Study on the efficacy and safety of alteplase in improving neurological function of patients with ischemic stroke

目的探讨急性缺血性脑卒中患者应用阿替普酶静脉溶栓的有效性和安全性。方法回顾性选取2004-2020年于大连医科大学附属第二医院确诊为急性缺血性脑卒中的1221例患者为研究对象,根据是否应用阿替普酶溶栓分为试验组(n=813)和对照组(n=408)。采用倾向性评分匹配控制混杂因素后,分析两组基线资料,采用美国国立卫生研究院卒中量表(NIHSS)评分差值判定阿替普酶静脉溶栓的有效性,入院与出院评分差值≥4分为神经功能改善,差值<4分为神经功能未改善。采用Logistic回归分析进一步验证阿替普酶静脉溶栓的有效性,绘制受试者工作特征(ROC)曲线评估模型的诊断效能。并针对两组人群进行亚组分析,探讨年龄、脑卒中严重程度、脑卒中分型、入院期间抗血小板药物使用情况等因素对阿替普酶溶栓的影响。以患者治疗后症状性颅内出血及死亡的发生率评估阿替普酶静脉溶栓的安全性。结果对倾向性评分匹配前后资料进行分析,试验组神经功能改善发生率高于对照组(P<0.05)。Logistic回归分析结果显示,在考虑入院NIHSS评分的影响下,应用阿替普酶溶栓有良好的效果[OR=5.200,95%CI:2.816~9.604,P<0.001]。Logistic模型曲线下面积为0.850,诊断价值较高。亚组分析显示,在缺血性脑卒中患者年龄亚组分析中,年龄<60岁患者与≥60岁患者是否使用阿替普酶溶栓对患者神经功能改善差异均具有统计学意义(P<0.05);在非轻型脑卒中亚组、大动脉粥样硬化型脑卒中亚组、病因分型未知亚组及未使用抗血小板药物亚组中,是否使用阿替普酶溶栓对患者神经功能改善差异具有统计学意义(P<0.05),在轻型脑卒中亚组、心源性亚组及使用抗血小板药物亚组中,是否使用阿替普酶溶栓对患者神经功能改善差异无统计学意义(P>0.05)。试验组与对照组患者治疗后症状性颅内出血及死亡发生率比较,差异无统计学意义(P>0.05)。结论急性缺血性脑卒中患者应用阿替普酶静脉溶栓安全有效,可改善患者神经功能。年龄<60岁、非轻型脑卒中患者、大动脉粥样硬化型脑卒中患者及入院后未用抗血小板药物的患者静脉溶栓有效性可能更好。

Objective To investigate the effectiveness and safety of intravenous thrombolysis with alteplase in patients with acute ischemic stroke.Methods Retrospectively select 1221 patients diagnosed with acute ischemic stroke in the Second Affiliated Hospital of Dalian Medical University from 2004 to 2020 as research subjects,and divid them into the experimental group(n=813)and the control group(n=408)according to whether or not thrombolysis with alteplase was applied.After adjusting for confounding factors by propensity score matching(PSM),the baseline data of the two groups were analyzed,and the effectiveness of IV thrombolysis with alteplase was determined by the difference between the National Institutes of Health Stroke Scale(NIHSS)scores on admission and on discharge,with a difference of≥4 being an improvement in neurological function,and that of<4 being a no-improvement in neurological function.Logistic regression analysis was used to further validate the effectiveness of IV thrombolysis with alteplase,and the diagnostic efficacy of the model was evaluated by plotting the ROC curve.Subgroup analyses were also performed for both groups to analyze the effects of the factors,including age,stroke severity,stroke classification and use of antiplatelet drugs during hospitalization,on alteplase thrombolysis.The safety of intravenous thrombolytic therapy in patients was evaluated in terms of symptomatic intracranial hemorrhage and death.Results The data before and after propensity score matching were analyzed,and the incidence of neurological function improvement was higher in experimental group than that in the control group(P<0.05).The results of Logistic regression analysis showed that the application of alteplase thrombolysis had a good effect when the effect of admission NIHSS score was considered[OR=5.200,95%CI:2.816~9.604,P<0.001].The area under the curve of the Logistic model was 0.850,which had a high diagnostic value.Subgroup analysis showed that in the age subgroup analysis of ischemic stroke patients,there was a statistically significant difference in the improvement of patients'neurological function between patients aged<60 years and those aged≥60 years with or without alteplase thrombolysis(P<0.05);in the non-mild stroke subgroup,large atherosclerotic stroke subgroup,subgroup of unknown etiology,and subgroup of no antiplatelet drugs,there was a statistically significant difference in the improvement of patients'neurological function between the patients with and those without alteplase thrombolysis(P<0.05).In the mild stroke subgroup,cardiogenic subgroup and the subgroup with the use of antiplatelet drugs,the difference in the improvement of neurological function of patients was not statistically significant(P>0.05)between the patients with and those without the use of alteplase thrombolysis.Comparing the experimental group with the control group,the difference in the incidence of symptomatic intracranial hemorrhage and death in patients after treatment was not statistically significant(P>0.05).Conclusion Intravenous thrombolysis with alteplase in patients with acute ischemic stroke is safe and effective,which improves patients'neurological function.The effectiveness of intravenous thrombolysis is better in patients of younger age(<60),with non-mild stroke,or large atherosclerotic stroke,and in patients without antiplatelet drugs.