尿激酶静脉溶栓后早期应用替罗非班对缺血性脑卒中患者安全性及预后的影响研究

背景　急性缺血性脑卒中是老年患者常见病、多发病，具有高致残率。急性缺血性脑卒中患者静脉应用尿激酶溶栓后临床疗效不确切，易反复。寻求尿激酶静脉溶栓治疗后积极有效的治疗方法显得至关重要。目的　探讨缺血性脑卒中患者尿激酶静脉溶栓后早期应用替罗非班的安全性及预后的影响因素，为缺血性脑卒中的治疗提供新思路。方法　回顾性收集2017年2月—2019年2月在宿州市第一人民医院行尿激酶静脉溶栓治疗的缺血性脑卒中患者（89例）的临床资料。根据患者是否早期应用替罗非班分为试验组（即采用尿激 酶联合替罗非班治疗）和对照组（即单用尿激酶治疗）。收集患者的一般资料，包括性别、年龄、高血压患病率、糖尿病患病率、心房颤动患病率、入院时血糖、脑卒中发病至治疗的时间（OTT）、入院时及入院第7天美国国立卫生研究院卒中量表（NIHSS）评分，入院7 d内发生出血、系统性出血、出血性脑梗死1型（HI-1）、出血性脑梗死2型（HI-2）、脑实质出血1型（PH-1）、脑实质出血2型（PH-2）的例数，入院3个月内死亡例数，以及治疗3个月时改良Rankin量表（mRS）评分。并以治疗3个月时mRS评分进行预后判定，≤1分为预后良好，≥2分为预后不良。整个研究采用倾向性评分匹配（PSM）控制混杂因素。并采用二分类Logistic回归分析探究缺血性脑卒中患者预后的影响因素。结果　PSM前，对照组57例，试验组32例。PSM后，对照组26例，试验组26例。两组患者PSM后性别、年龄、高血压患病率、糖尿病患病率、心房颤动患病率、入院时血糖、OTT、入院时NIHSS评分比较，差异无统计学意义（P>0.05）。因此采用PSM后资料进行进一步分析。试验组患者入院第7天NIHSS评分低于对照组（Z=-2.754，P=0.006）。对照组、试验组患者入院第7天NIHSS评分均低于入院时NIHSS评分，差异有统计学意义（Z值分别为-2.321、-4.121，P均0.05）。两组患者入院7 d内均无HI-1、PH-1发生。试验组患者预后良好率高于对照组，治疗3个月时mRS评分低于对照组（P<0.05）。单因素Logistic回归分析结果显示，年龄〔OR=0.920，95%CI（0.848，1.000），P=0.049〕、入院时NIHSS评分〔OR=0.538，95%CI（0.362，0.798），P=0.002〕、早期应用替罗非班注射液〔OR=11.271，95%CI（1.833，69.317），P=0.009〕是缺血性脑卒中患者预后的影响因素。结论　急性缺血性脑卒中患者尿激酶静脉溶栓后早期应用替罗非班注射液安全有效，可改善患者早期神经功能及预后。

Safety and Outcome in Ischemic Stroke Patients with Early Intravenous Administration of Tirofiban Following Urokinase for Thrombosis

Background Acute ischemic stroke is a common and frequently occurring disease in the elderly and is associated with high mortality.But there is no accurate response to intravenous thrombolytic therapy using urokinase in such patients,and the disease is easily to recur.So it is crucial to seek active and effective treatment after intravenous thrombolytic therapy with urokinase.Objective To investigate the factors associated with the safety and outcome in ischemic stroke patients receiving early administration of tirofiban after urokinase for intravenous thrombolysis,providing a novel perspective for the treatment of this disease.Methods We conducted a retrospective study on 89 cases of ischemic stroke treated in Suzhou First People's Hospital between February 2017 and February 2019,and classified them into experimental group(early use of tirofiban after urokinase for intravenous thrombolysis)and control group(use of urokinase for intravenous thrombolysis).We collected their clinical data,including gender,age,prevalence of hypertension,diabetes and atrial fibrillation,admission plasma glucose level,onset-treatment-time,the NIHSS score at admission and 7th day after admission,the number of patients with bleeding,systemic bleedings,hemorrhagic infarction type 1(HI-1),HI-2,parenchymal hematoma type 1(PH-1)or PH-2 in 7 days,and deaths in 3 months after admission,and mRS scores(≤1 was considered a favorable outcome,and≥2 was considered an unfavorable outcome)at 3 months after treatment.We used propensity score matching to control the confounding factors,and used binary Logistic regression to analyze the factors associated with the outcome.Results By propensity score matching,26 of the 32 cases in the experimental group and 26 of the 57 cases in the control group were finally included for further analysis,with no significant inter-group differences in sex ratio,mean age,prevalence of hypertension,diabetes,and atrial fibrillation,mean admission plasma glucose level,onset-treatment-time,and admission NIHSS score(P>0.05).The mean NIHSS score on the 7th day after admission decreased significantly in the control group(Z=-2.321,P<0.05)as well as in the experimental group(Z=-4.121,P<0.05),and it decreased even more significantly in the experimental group(Z=-2.754,P=0.006).The incidence of bleeding,systemic bleedings,HI-2 and PH-2 within 7 days after admission and mortality rate in 3 months did not differ significantly in two groups(P>0.05).No HI-1 and PH-1 were found in all patients during the 7 days.The experimental group had a lower mean mRS score,indicating that a better outcome was achieved in general(P<0.05).Univariate Logistic regression analysis suggested that age〔OR=0.920,95%CI(0.848,1.000),P=0.049〕,NIHSS score at admission〔OR=0.538,95%CI(0.362,0.798),P=0.002〕and early treatment with tirofiban〔OR=11.271,95%CI(1.833,69.317),P=0.009〕were associated with the outcome.Conclusion Intravenous tirofiban immediately after urokinase seems to be safe and potentially more effective in early improvement of neurological functions and 3-month outcome compared with urokinase alone.