阿加曲班联合阿替普酶治疗急性缺血性脑卒中的系统评价及GRADE证据级别评价

Systematic review and GRADE evaluation in treatment of acute ischemic stroke with combination therapy of argatroban and alteplase

目的 系统评价阿加曲班(AGB)联合阿替普酶(rt-PA)治疗急性缺血性脑卒中(AIS)的有效性和安全性。方法检索PubMed、Embase、Cochrane Library、中国生物医学文献数据库(CBM)、中国学术期刊全文数据库(CNKI)、万方数据库(Wanfang Data)和维普中文期刊全文数据库(VIP),搜集关于AGB联合rt-PA治疗AIS的随机对照试验(RCT),检索时限均由建库至2022年6月28日。由2名研究者独立筛选文献、提取资料,并利用RevMan 5.3软件进行Meta分析、GRADE系统进行证据质量评估分级。结果 共纳入22个RCTs,包括1 921例患者。Meta分析结果显示:与对照组比较,试验组可提高总有效率[RR=1.22,95%CI(1.16,1.27)、P<0.000 01],改善美国国立卫生研究院卒中量表(NIHSS)评分[MD=-1.92,95%CI(-2.46,-1.38),P<0.000 01]、Barthel指数评分[MD=8.97,95%CI(6.64,11.30),P<0.000 01]和改良Rankin量表评分[MD=-0.58,95%CI(-1.05,-0.10),P=0.02];试验组与对照组比较,出血发生率无明显增加[Peto OR=0.66,95%CI(0.44,1.01),P=0.05]、颅内出血发生率无明显增加[Peto OR=0.66,95%CI(0.32,1.36),P=0.26],两组差异均无统计学意义。GRADE评估为中、低或极低质量证据,推荐强度为弱推荐。结论 当前证据显示,AGB联合rt-PA治疗AIS具有一定的有效性和安全性,但因纳入研究证据等级较低,此结论仍需更多高质量、高标准的证据。

Objective To evaluate the efficacy and safety of acute ischemic stroke(AIS) with combination therapy of argatroban and alteplase. Methods Data were electronically searched from PubMed, Embase, Cochrane Llibrary, CBM, CNKI, Wanfang Data and VIP from the establishment of the databases to June 28, 2022 for randomized controlled trials(RCT) of AIS with combination therapy of argatroban and alteplase. Two researchers independently screened the literature and extracted the data. Meta-analysis was performed by RevMan 5.3 software, evidence quality assessment and classification was made with GRADE system. Results A total of 22 RCTs involving 1 921 patients were included. The results of Meta-analysis suggested that, compared with the control group(therapy of alteplase), experimental group(therapy of argatroban and alteplase) could improve the clinical efficacy [RR = 1.22,95%CI(1.16, 1.27)、P < 0.000 01], significantly improve the difference before and after treatment in NIHSS scores [MD =-1.92,95%CI(-2.46,-1.38), P < 0.000 01], Barthel scores [MD = 8.97, 95%CI(6.64, 11.30), P < 0.000 01] and mRS scores [MD =-0.58,95%CI(-1.05,-0.10), P = 0.02]. Compared with the control group, the incidence of hemorrhage in the experimental group was not significantly increased [Peto OR = 0.66, 95%CI(0.44, 1.01), P = 0.05], and the incidence of intracranial hemorrhage was not significantly increased [Peto OR = 0.66, 95%CI(0.32, 1.36), P = 0.26]. There was no significant difference between the two groups.GRADE assessment was moderate, low or very low quality evidence, and recommendation strength was weak recommendation.Conclusion The current evidence indicates that combination therapy of argatroban and alteplase is effective and safe in the treatment of AIS. However, due to the low level of evidence in the included studies, this conclusion still needs more high-quality and high-standard research evidence.