Intra-arterial thrombolysis after successful endovascular reperfusion for large vessel occlusion stroke: A meta-analysis of randomized seven controlled trials

Abstract

Background

Although thrombectomy is the standard of care for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO), many patients fail to achieve disability-free recovery, highlighting the need for adjunctive therapy to improve outcomes.

Purpose

This systematic review and meta-analysis aimed to compare intra-arterial thrombolysis (IAT) and placebo following the successful recanalization of AIS-LVO.

Materials and Methods

A systematic literature review of four databases was performed. Categorical and continuous outcomes were calculated using Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs), respectively. Any potential heterogeneity was resolved through leave-one-out influence analysis. Risk of bias was assessed using the RoB2 tool. Our study was not registered in PROSPERO. The primary analysis included three published RCTs; four additional trials, including posterior circulation or preliminary data, were incorporated in sensitivity analyses to validate robustness.

Results

A total of three trials with enrolled patients 1187 were included in the study. Four additional trials were also included only for sensitivity analysis. The findings showed that patients who received IAT had a significantly higher rate of 90-day functional excellence (RR = 1.15, 95%CI = 1.01–1.3, P = .032, I ²  = 0.0%) than the control group. There was no significant difference between the two groups regarding functional independence, mortality, symptomatic or any intracranial hemorrhage, and total adverse events. There was a significantly higher functional excellence rate in IAT group compared with control group in studies that included patients with expanded thrombolysis in cerebral infarction score (eTICI) score of 2b-3 versus 2c-3 (RR = 1.5, 95%CI = 1.23–1.82 P = .016, I ²  = 0.0%) and female patients derived more benefit from IAT than placebo (RR = 1.42, 95%CI = 1.15–1.75, P = .001, I ²  = 0.0%). Notably, there was no significant heterogeneity across any primary and secondary outcomes.

Conclusion

In patients with AIS-LVO presenting within 24 h of time last seen well who achieved successful endovascular recanalization, IAT significantly improved the likelihood of functional excellence at three months without hemorrhagic risk. Further research is warranted to validate these findings.