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

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. 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. 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; I = 0%) and good functional outcome (RR = 1.18; 95%CI:1.05-1.33; I = 70%). IVT was associated with increased odds of reduced disability (common OR = 1.3; 95%CI:1.15-1.46; I = 0%) and increased risk of sICH (RR = 2.75; 95%CI:1.49-5.05; I = 0%). The rates of any ICH and all-cause mortality were similar between the two groups. No significant subgroup differences were documented. IVT in the extended time window improved functional outcomes without increasing mortality, despite a higher rate of sICH.