尿激酶溶栓治疗急性缺血性卒中的疗效和安全性:基于前瞻队列的剂量探索研究  

Effectiveness and safety of intravenous urokinase for acute ischemic stroke:a dose explorative study based on a prospective cohort

作　　者：张楚潍 王新红 陈会生 Zhang Chuwei;Wang Xinhong;Chen Huisheng(Department of Neurology,General Hospital of Northern Theater Command,Shenyang110016,China)

机构地区：[1]北部战区总医院神经内科,沈阳110016

出　　处：《中华神经科杂志》2024年第12期1342-1352,共11页Chinese Journal of Neurology

基　　金：国家重点研发计划(2017YFC1308200)。

摘　　要：目的分析中国发病4.5 h内急性缺血性卒中患者应用尿激酶溶栓的最佳剂量。方法基于中国发病4.5 h内缺血性卒中的静脉溶栓登记研究(INTRECIS)队列,回顾性连续收集2017年4月1日至2019年7月1日接受尿激酶溶栓的患者。按照溶栓剂量除以体重的三分位数划分为低剂量组[(1.00~1.67)万单位/kg]、中剂量组[(1.68~2.33)万单位/kg]、高剂量组[(2.34~3.00)万单位/kg]。根据发病年龄、性别、基线美国国立卫生研究院卒中量表(NIHSS)评分设置不同亚组。主要疗效结局指标为极好预后,定义为90 d改良Rankin量表(mRS)评分0~1分。次要疗效结局指标包括良好预后(90 d mRS评分0~2分)、90 d mRS评分分布、NIHSS评分变化(基线与1 d、14 d比较)。主要安全结局指标为症状性颅内出血(sICH)发生率,次要安全结局指标包括90 d内卒中复发率、全因病死率及任意出血事件。结果共有1144例患者被纳入分析,其中低剂量组549例,中剂量组509例,高剂量组86例。高剂量组极好预后比例显著高于低剂量组[79.07%(68/86)比67.03%(368/549),OR=2.427,95%CI 1.280~4.587,P=0.007]、中剂量组[79.07%(68/86)比70.53%(359/509),OR=1.942,95%CI 1.023~3.690,P=0.043]。3组之间sICH发生率相当[高剂量组比低剂量组:1.16%(1/86)比2.00%(11/549),OR=0.607,95%CI 0.071~5.153,P=0.648;高剂量组比中剂量组:1.16%(1/86)比0.79%(4/509),OR=0.330,95%CI 0.101~1.074,P=0.596],差异无统计学意义。亚组分析结果显示,在高龄人群(≥60岁)[高剂量组比低剂量组:80.70%(46/57)比63.07%(222/352),OR=3.401,95%CI 1.500~7.752,P=0.003;高剂量组比中剂量组:80.70%(46/57)比69.63%(227/326),OR=2.381,95%CI 1.074~5.291,P=0.033]、中等程度卒中患者(NIHSS评分:4~16分)[高剂量组比低剂量组:79.07%(34/43)比62.61%(211/337),OR=2.604,95%CI 1.190~5.682,P=0.017;高剂量组比中剂量组:79.07%(34/43)比65.02%(184/283),OR=2.315,95%CI 1.055~5.097,P=0.036]、大动脉粥样硬化型患者[高剂量组比低剂量组:81.40%(35Objective To analyze the optimal dose of urokinase(UK)for intravenous thrombolysis in Chinese patients with acute ischemic stroke within 4.5 hours of onset.Methods Based on the intravenous thrombolysis registry for Chinese ischemic stroke within 4.5 hours of onset(INTRECIS)cohort,consecutive patients who received intravenous UK from April 1,2017 to July 1,2019 were retrospectively collected.According to the tertile dose of UK per body weight,eligible patients were divided into low dose group[(1.00-1.67)×10^(4) international unit per kilogram],moderate dose group[(1.68-2.33)×10^(4) international unit per kilogram]and high dose group(2.34-3.00)×10^(4) international unit per kilogram].Furthermore,subgroups were analyzed according to age,gender,and baseline National Institutes of Health Stroke Scale(NIHSS)scores.The primary efficacy outcome was excellent functional outcome,defined as a 90-day modified Rankin Scale(mRS)score of 0-1.The secondary efficacy outcomes included favorable functional outcome(mRS score of 0-2 at 90 days),mRS score distribution at 90 days and changes in NIHSS score at 1 day and 14 days,compared with the baseline.The primary safety outcome was symptomatic intracranial hemorrhage(sICH),and the secondary safety outcomes included recurrence of stroke within 90 days,all-cause mortality and any random bleeding events.Results A total of 1144 patients were included in the analysis:549 in the low dose group,509 in the moderate dose group and 86 in the high dose group.The proportion of excellent functional outcome was higher in the high dose group,compared with the low dose group[79.07%(68/86)vs 67.03%(368/549),OR=2.427,95%CI 1.280-4.587,P=0.007]and the moderate dose group[79.07%(68/86)vs 70.53%(359/509),OR=1.942,95%CI 1.023-3.690,P=0.043].The incidence of sICH was similar among the 3 groups[high dose group vs low dose group:1.16%(1/86)vs 2.00%(11/549),OR=0.607,95%CI 0.071-5.153,P=0.648;high dose group vs moderate dose group:1.16%(1/86)vs 0.79%(4/509),OR=0.330,95%CI 0.101-1.074,P=0.596].The subgroup a

关 键 词：卒中 尿激酶 药物剂量计算 预后 静脉溶栓 

分 类 号：R743.3[医药卫生—神经病学与精神病学]