Efficacy And Safety Of Intravenous Antithrombotic Drugs Combined With Intravenous Thrombolysis Or Mechanical Thrombectomy In Acute Ischemic Stroke: A Systematic Review And Meta-analysis

Objective:This meta-analysis aims to evaluate the effectiveness and security of intravenous antithrombotic therapy in combination with either thrombolysis or mechanical thrombectomy for patients suffering from acute ischemic stroke.Methods:English and Chinese databases,including Pub Med,Cochrane Library,Embase,CNKI,Wanfang,and VIP,were systematically searched for randomized controlled trials or prospective cohort studies related to antithrombotic drugs and acute ischemic stroke published from the establishment of the database to September2022.Safety outcome measures:symptomatic intracranial hemorrhage,any intracranial hemorrhage,and all-cause mortality at 3 months.Effective outcome indicators were:Modified Rankin scale(m RS)score and successful recanalization at90 days.Inclusion criteria included:(1)patients with acute ischemic stroke receiving intravenous thrombolysis or mechanical thrombectomy;(2)The intervention group received intravenous antithrombotic drugs in the acute phase;(3)The control group was placebo or blank control;(4)The duration of follow-up was at least 3 months;(5)Randomized controlled or prospective cohort studies.Exclusion criteria:(1)follow-up data less than 90%;(2)ongoing research;(3)Full text research cannot be obtained;(4)Case reports,animal experiments,personal experience summaries,reviews,meta-analyses,etc.Employing the Der Simonian&Laird random effect model and Inverse-Variance fixed effect model,the real-world risk(RR)and 95%confidence interval(CI)were calculated for each outcome.The quality of randomized controlled trials and prospective cohort studies was assessed using the revised Oxford Quality Scoring System(Jadad Scale)and Newcastle-Ottawa Scale(NOS).A variety of testing methods,such as heterogeneity test,combined effect size analysis,subgroup analysis,sensitivity analysis and bias test,were employed to meta-analyze the collected data.Result:1.This meta-analysis,based on the literature’s inclusion and exclusion criteria,encompassed 3 randomized controlled trials and 10 prospective cohort studies,amounting to 4115 individuals suffering from acute ischemic stroke.2.No significant heterogeneity was seen between the 13 studies,with all of them reporting the outcome of symptomatic intracranial hemorrhage(I~2=28%,P=0.17).A fixed-effect model was employed to amalgamate the effect sizes,and the results indicated that intravenous antithrombotic drugs had no effect on the risk of symptomatic intracranial hemorrhage[RR=1.04,95%CI(0.83,1.30),P=0.21].Subgroup analysis of different treatments showed intravenous antithrombotic drugs combined with intravenous thrombolysis[RR=0.60,95%CI(0.25,1.45),P=0.26)or mechanical thrombectomy[RR=1.07,95%CI(0.85,1.36),P=0.55]did not increase the risk of symptomatic intracranial hemorrhage.3.In subgroup analysis according to treatment method,functional outcome m RS(0-1)at 3 months was significantly improved in the group receiving intravenous antithrombotic drugs combined with intravenous thrombolysis compared with intravenous thrombolysis alone[RR=1.56,95%CI(1.20,2.03),P=0.001],and the difference was statistically significant.However,the functional outcome m RS(0-1)was not improved in the group treated with intravenous antithrombotic drugs plus mechanical thrombectomy compared with the group treated with mechanical thrombectomy alone[RR=1.08,95%CI(0.96,1.22),P=0.21].4.Thirteen studies reported all-cause deaths at 3 months.In these studies,there was no significant heterogeneity(I~2=0%,P=0.61).The results showed that the group treated with intravenous antithrombotic drugs combined with intravenous thrombolysis or mechanical thrombolysis had a significant reduction in all-cause mortality at 3 months compared with those treated with intravenous thrombolysis or mechanical thrombolysis alone[RR=0.85,95%CI(0.74,0.99),P=0.66],and the difference was not statistically significant.In addition,in a subgroup analysis,the group receiving intravenous antithrombotic drugs combined with mechanical thrombectomy had improved all-cause mortality compared with those receiving mechanical thrombectomy alone[RR=0.85,95%CI(0.73,0.99),P=0.04].Intravenous antithrombotic drugs combined with intravenous thrombolytic therapy did not reduce the risk of death at 3 months compared with intravenous thrombolytic therapy alone[RR=0.96,95%CI(0.55,1.68),P=0.90].5.For any intracranial hemorrhage and successful recanalization outcome,intravenous antithrombotic drugs combined with intravenous thrombolysis or mechanical thrombectomy treatment regimen was not significantly different from the control group.Conclusion:(1)Intravenous antithrombotic agents do not increase the incidence of symptomatic intracranial hemorrhage or any intracranial hemorrhage in patients with acute ischemic stroke treated with intravenous thrombolysis or mechanical thrombectomy.(2)Intravenous antithrombotic drugs combined with intravenous thrombolytic therapy could improve the neurofunctional outcome(m RS 0-1)at 3 months of ischemic stroke.(3)Intravenous antithrombotic therapy combined with mechanical thrombectomy reduced all-cause mortality at 3 months in patients with acute ischemic stroke.