阿替普酶静脉溶栓后联合替罗非班治疗急性缺血性脑卒中安全性及有效性的Meta分析

Meta-analysis of safety and efficacy of alteplase combined with tirofiban treatment in acute ischemic stroke

目的评价阿替普酶(rt-PA)静脉溶栓后联合替罗非班治疗急性缺血性脑卒中(AIS)的安全性及有效性。方法检索PubMed、Embase、Web of Science、Cochrane图书馆、万方数据库、中国知网中截至到2021年6月的AIS患者rt-PA静脉溶栓后联合替罗非班(联合用药组)与单纯rt-PA静脉溶栓治疗(单纯rt-PA组)的对照研究。纳入的随机对照研究按照Cochrane系统评价手册进行文献质量评价,非随机对照研究采用纽卡斯尔-渥太华量表(NOS)进行文献质量评价,并根据rt-PA静脉溶栓后是否出现神经功能恶化启用替罗非班时机的不同进行亚组分析。结果共纳入9项研究,共计1012例患者。联合用药组与单纯rt-PA组颅内出血(ICH)、症状性脑出血(sICH)、其他系统出血发生率及死亡率差异无统计学意义(RD=0.004,95%CI:-0.028~0.035,P=0.818;RD=-0.003,95%CI:-0.022~0.016,P=0.739;RD=-0.001,95%CI:-0.028~0.025,P=0.920;RD=0.003,95%CI:-0.024~0.029,P=0.848)。与单纯rt-PA组比较,出现神经功能恶化后启用替罗非班亚组(RD=0.027,95%CI:-0.022~0.075,P=0.278;RD=0.001,95%CI:-0.031~0.032,P=0.960;RD=0.000,95%CI:-0.025~0.025,P=1.000;RD=-0.004,95%CI:-0.053~0.045,P=0.863)、未出现神经功能恶化时提早启用替罗非班亚组(RD=-0.013,95%CI:-0.054~0.028,P=0.544;RD=-0.006,95%CI:-0.030~0.018,P=0.630;RD=-0.002,95%CI:-0.040~0.036,P=0.916;RD=0.008,95%CI:-0.022~0.037,P=0.615)ICH、sICH、其他系统出血发生率及死亡率差异无统计学意义。联合用药组与单纯rt-PA组预后良好率差异有统计学意义(RD=0.223,95%CI:0.150~0.295,P=0.000)。与单纯rt-PA组比较,出现神经功能恶化后启用替罗非班亚组、未出现神经功能恶化时提早启用替罗非班亚组预后良好率差异有统计学意义(RD=0.230,95%CI:0.135~0.325,P=0.000;RD=0.213,95%CI:0.101~0.325,P=0.000)。结论AIS患者rt-PA静脉溶栓后早期联合替罗非班及rt-PA静脉溶栓后24 h内发生神经功能恶化后联合替罗非班治疗均安全、有效。

Objective To evaluate the safety and efficacy of alteplase(rt-PA)combined with tirofiban treatment in acute ischemic stroke(AIS).Methods PubMed,Embase,Web of Science,Cochrane Library,Wan fang databases and CNKI were searched for comparative studies on AIS patients treated with combined rt-PA intravenous thrombolysis and tirofiban therapy(combined group)vs rt-PA alone(rt-PA group)up to June 2021.Cochrane systematic review manual method was used to evaluate the literature quality of randomized controlled studies.The Newcastle Ottawa scale(NOS)was used to evaluate the literature quality of non-randomized controlled studies.Subgroup analysis was performed according to whether tirofiban was used when neurological deterioration occurred after rt-PA intravenous thrombolysis.Results A total of 9 studies with 1012 patients were included.There was no significant difference in the incidence of intracranial hemorrhage(ICH),symptomatic cerebral hemorrhage(sICH),other systemic bleeding and mortality between combined group and the rt-PA group(RD=0.004,95%CI:-0.028-0.035,P=0.818;RD=-0.003,95%CI:-0.022-0.016,P=0.739;RD=-0.001,95%CI:-0.028-0.025,P=0.920;RD=0.003,95%CI:-0.024-0.029,P=0.848).Compared with those in rt-PA group,there was no significant difference in the incidence of ICH,s ICH,other systemic bleeding and mortality in the tirofiban enabled after neurological deterioration subgroup(RD=0.027,95%CI:-0.022-0.075,P=0.278;RD=0.001,95%CI:-0.031-0.032,P=0.960;RD=0.000,95%CI:-0.025-0.025,P=1.000;RD=-0.004,95%CI:-0.053-0.045,P=0.863)and tirofiban enabled without neurological deterioration subgroup(RD=-0.013,95%CI:-0.054-0.028,P=0.544;RD=-0.006,95%CI:-0.030-0.018,P=0.630;RD=-0.002,95%CI:-0.040-0.036,P=0.916;RD=0.008,95%CI:-0.022-0.037,P=0.615).There was significant difference in the rate of good prognosis between combined group and rt-PA group(RD=0.223,95%CI:0.150-0.295,P=0.000).Compared with the rt-PA group,there was significant difference in the rate of good prognosis in the tirofiban enabled after neurological deterioration subgroup and tirofiban enabled without neurological deterioration subgroup(RD=0.230,95%CI:0.135-0.325,P=0.000;RD=0.213,95%CI:0.101-0.325,P=0.000).Conclusion For AIS patients,the combination of tirofiban in the early stage after rt-PA intravenous thrombolysis and the combination of tirofiban when neurological deterioration occurred within 24 h after rt-PA intravenous thrombolysis is both safe and effective.