阿加曲班治疗急性缺血性卒中疗效及安全性的系统评价及Meta分析

The efficacy and safety of argatroban in the treatment of acute ischemic stroke:a systematic review and Meta-analysis

目的:目前阿加曲班在急性缺血性卒中(acute ischemic stroke,AIS)中的疗效和安全性尚存在争议,临床应用仍存在较大分歧。本文将针对阿加曲班治疗AIS的疗效和安全性展开系统性评价及Meta分析。方法:计算机检索通过PubMed、The Cochrane library、Embase、ClinicalTrials.gov、中国知网(China National Knowledge Infrastructure,CNKI)、中国生物医学文献数据库(China Biology Medicine disc,CBM)、维普网及万方数据知识服务平台收集应用阿加曲班治疗AIS的全部文献,检索的设定时间截至2022年4月。由2名受过培训的研究人员对文献进行筛选、数据提取和偏倚风险评估。采用RevMan 5.4软件对数据进行Meta分析。结果:共有25篇文献纳入本次Meta分析,共包含AIS患者4696例(其中阿加曲班组2271例,对照组2425例)。Meta分析结果显示:阿加曲班能促进AIS患者早期神经功能改善(OR=2.69,95%CI=1.66~4.34,P<0.001),减少早期神经功能恶化(OR=0.42,95%CI=0.29~0.60,P<0.001),但对于90 d改良Rankin量表(modified Rankin scale,mRS)评分0~1分患者比例(P=0.080)、90 d mRS评分0~2分患者比例(P=0.230)及卒中复发率(P=0.190)均无明显影响;亚组分析结果显示,阿加曲班联合口服抗血小板药物能改善90 d mRS评发0~2的患者比例,差异具有统计学意义(OR=1.55,95%CI=1.17~2.05,P=0.003);在安全性方面,阿加曲班及对照组在任何颅内出血(P=0.730)、症状性颅内出血(P=0.990)、系统性出血(P=0.150)及死亡率(P=0.990)上均无统计学差异。结论:阿加曲班可改善AIS患者早期神经功能预后,且不增加患者的出血风险及死亡率。

Objective:The efficacy and safety of argatroban in acute ischemic stroke(AIS)remains controversial.Our study aims to conduct a systematic review and Meta-analysis on the efficacy and safety of argatroban in AIS.Methods:Relevant literatures were searched from the databases of PubMed,The Cochrane Library,Embase,ClinicalTrials.gov,CNKI,CBM,VIP and Wanfang until April2022.Two trained researchers screened the literature,extracted data and assessed the bias risk independently.The Meta-analysis was performed using RevMan 5.4 software.Results:A total of 25 studies were enrolled in the Meta-analysis,including 4696 AIS patients(2271 cases in the argatroban group and 2425 cases in the control group).Overall Meta-analysis showed that argatroban significantly improved early neurological function recovery(OR=2.69,95%CI=1.66-4.34,P<0.001),and reduced early neurological deterioration(OR=0.42,95%CI=0.29-0.60,P<0.001).However,there was no significant influence on the proportion of patients with modified Rankin Scale(mRS)score of 0-1(P=0.080),the proportion of patients with mRS score of 0-2(P=0.230)and recurrence rate of stroke(P=0.190).The subgroup analysis showed argatroban combined with oral antiplatelet drugs was associated with higher incidence of 90-day mRS 0-2(OR=1.55,95%CI=1.17-2.05,P=0.003).There was no significant difference in the incidence of any intracranial hemorrhage(P=0.730),symptomatic intracranial hemorrhage(P=0.990),systemic bleeding(P=0.150)and mortality(P=0.990).Conclusion:Argatroban may improve the early neurological func-tion recovery in AIS patients without increasing the risk of bleedingand mortality.