Safety and efficacy of intravenous thrombolytic therapy in the extended window up to 24 hours: A systematic review and meta-analysis.

Objective: About 25% of patients with acute ischemic stroke (AIS) present within the intravenous thrombolytic (IVT) therapeutic window of <4.5 h. This study is to elucidate the safety and efficacy of IVT in the extended therapeutic window (ETW) in patients with AIS.

Methods: Using PRISMA guidelines, a systematic review was conducted using PubMed, Embase, and Scopus. A rigorous risk of bias assessment was conducted using the RoB2 tool. Rates of excellent and good functional outcome (mRS 0-1 and mRS 0-2) at 90 days, symptomatic intracranial hemorrhage (sICH), and mortality at 90 days were pooled using generalized linear mixed model and compared with controls. Meta-analyses were conducted employing random-effect models with risk ratio (RR) and 95% confidence intervals (CIs). Subgroup analysis was performed to assess the effect of imaging modalities used for patient selection.

Results: Eight randomized controlled trials (n = 2221, 59% male) were included. At 90 days IVT showed higher rates of functional recovery: mRS 0-1: RR 1.21 95% CI 1.1-1.34, p < 0.001, and mRS 0-2: RR 1.11 95% CI 1.03-1.18, p = 0.004. Rate of mortality at 90 day was not different between groups: RR 1.17 95% CI 0.93-1.48, p = 0.17. However, the rate of sICH was higher among IVT group: RR 2.93 95% CI 1.53-5.6, p = 0.001. Subgroup analysis showed higher mRS 0-1 among patients who were selected based on perfusion imaging (p < 0.05).

Interpretation: The use of IVT in AIS in ETW is beneficial especially with the use of perfusion imaging for patients' selection.