尤瑞克林用药时长对急性缺血性脑卒中患者疗效和安全性的影响——RESK研究亚组分析

The effect of treatment duration with human urinary kallidinogenase on the efficacy and safety of acute ischemic stroke:a subgroup analysis of RESK study

目的探究尤瑞克林不同用药时长对急性缺血性脑卒中患者疗效和安全性的影响。方法本研究为RESK研究的亚组分析。从2015年8月到2020年6月共纳入65个中心的990例脑卒中患者,根据尤瑞克林用药时间长短分为短时用药组(用药8 d,n=185)和长时用药组(用药15 d和21 d,n=805)。分析患者90 d改良Rankin量表(mRS)评分为0分、0~1分和0~2分的患者比例,22 d美国国立卫生研究院卒中量表(NIHSS)评分较基线的变化,90 d Barthel指数≥95分患者比例和不良事件发生率。采用χ2检验、单因素和多因素Logistic回归分析等进行组间比较。结果多因素回归分析结果显示,短时用药组和长时用药组90 d mRS评分0~2分的患者比例[74.1%(137/185)比75.0%(604/805);OR=1.047,95%CI 0.676~1.620,P=0.838]和22 d NIHSS评分较基线的变化[(4.60±2.00)分比(4.26±2.80)分;OR=-0.390,95%CI-1.125~0.344,P=0.297],差异均无统计学意义;90 d mRS评分0~1分的患者比例[48.1%(89/185)比59.1%(476/805);OR=0.674,95%CI 0.463~0.983,P=0.041]和90 d Barthel指数≥95分患者比例[43.6%(79/181)比55.1%(442/802);OR=0.614,95%CI 0.420~0.897,P=0.012],在短时用药组均显著低于长时用药组。两组不良事件的发生率差异无统计学意义。结论对于急性缺血性脑卒中患者,尤瑞克林连续用药8 d即可改善患者近期(22 d NIHSS评分)和远期疗效(90 d mRS评分0~2分),且安全耐受。在条件允许的情况下,增加尤瑞克林用药时长可显著提高患者远期无残疾率(90 d mRS评分0~1分)和生活质量(90 d Barthel指数),且不增加不良事件风险。

Objective To explore the impact of treatment duration with human urinary kallidinogenase(HUK)on the efficacy and safety of acute ischemic stroke(AIS).Methods In this subgroup analysis of RESK study,a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group(HUK for 8 days,n=185)or long medication group(HUK for 15 days or 21 days,n=805).The proportions of patients with modified Rankin Scale(mRS)score of 0,0-1,0-2 at 90 days,National Institutes of Health Stroke Scale(NIHSS)score change from baseline to 22 days,the proportions of patients with Barthel index(BI)≥95 at 90 days,and the incidences of adverse events were analyzed.Comparisons between groups were conducted using chi-square test,single factor and multivariate Logistic regression analysis,etc.Results Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2[74.1%(137/185)vs 75.0%(604/805);OR=1.047,95%CI 0.676-1.620,P=0.838]and 22-day NIHSS score change from baseline(4.60±2.00 vs 4.26±2.80;OR=-0.390,95%CI-1.125-0.344,P=0.297)showed no statistically significant difference between the short medication and long medication groups;the proportions of patients with 90-day mRS score of 0-1[48.1%(89/185)vs 59.1%(476/805);OR=0.674,95%CI 0.463-0.983,P=0.041]and 90-day BI≥95[43.6%(79/181)vs 55.1%(442/802);OR=0.614,95%CI 0.420-0.897,P=0.012]were significantly lower in the short medication group than in the long medication group.There was no statistically significant difference in the incidences of adverse events between these 2 groups.Conclusions In AIS patients,consecutive 8-day dosing of HUK improved immediate(22-day NIHSS score)and long-term outcome(90-day mRS score 0-2)and was safely tolerated.When applicable,extended duration of HUK could improve long-term disability-free rate(90-day mRS score 0-1)and quality of life(90-day BI)without increasing the risk of adverse events.