Efficacy and Safety of Intravenous Thrombolysis in the Extended Time Window for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Background/Objectives: While intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke (AIS) within 4.5 h of symptom onset, many patients present beyond this time window. Recent trials suggest that IVT may be both effective and safe in selected patients treated after the standard time window. Methods: We searched MEDLINE, Scopus, and ClinicalTrials.gov for randomized-controlled clinical trials (RCTs) and individual patient-data meta-analyses (IPDMs) of RCTs comparing IVT plus best medical treatment (BMT) to BMT alone in AIS patients who were last-known-well more than 4.5 h earlier. The primary efficacy outcome was a 90-day excellent functional outcome modified Rankin Scale (mRS)-scores of 0–1. Secondary efficacy outcomes included good functional outcome (mRS-scores 0–2) and reduced disability (≥1-point reduction across all mRS-strata). The primary safety outcome was symptomatic intracranial hemorrhage (sICH); secondary safety outcomes were any ICH and 3-month all-cause mortality. Subgroup analyses were performed stratified by different thrombolytics, time-windows, imaging modalities, and affected circulation. Results: Nine studies were included, comprising 1660 patients in the IVT-group and 1626 patients in the control-group. IVT significantly improved excellent functional outcome (RR = 1.24; 95%CI:1.14–1.34; I2 = 0%) and good functional outcome (RR = 1.18; 95%CI:1.05–1.33; I2 = 70%). IVT was associated with increased odds of reduced disability (common OR = 1.3; 95%CI:1.15–1.46; I2 = 0%) and increased risk of sICH (RR = 2.75; 95%CI:1.49–5.05; I2 = 0%). The rates of any ICH and all-cause mortality were similar between the two groups. No significant subgroup differences were documented. Conclusions: IVT in the extended time window improved functional outcomes without increasing mortality, despite a higher rate of sICH.