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

摘要:

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4 696例（其中阿加曲班组2 271例，对照组2 425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。

Abstract:

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 April 2022. 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 4 696 AIS patients（2 271 cases in the argatroban group and 2 425 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 function recovery in AIS patients without increasing the risk of bleeding and mortality.