IV Thrombolysis in the Extended Time Window for Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis

Area of Science:

• Neurology
• Cardiovascular Medicine
• Clinical Trials

Background:

• Intravenous thrombolysis (IVT) is standard for acute ischemic stroke (AIS) within 4.5 hours.
• Many AIS patients present beyond the standard treatment window.
• Emerging evidence suggests IVT may benefit selected patients in extended time windows.

Purpose of the Study:

• To systematically evaluate the efficacy and safety of IVT in AIS patients presenting more than 4.5 hours after last known well.
• To assess functional outcomes and safety events associated with extended-window IVT.

Main Methods:

• Systematic search of RCTs and individual patient data meta-analyses from MEDLINE, Scopus, and ClinicalTrials.gov.
• Comparison of IVT plus best medical therapy (BMT) versus BMT alone.
• Primary efficacy outcome: excellent functional outcome (mRS 0-1) at 90 days; primary safety outcome: symptomatic intracranial hemorrhage (sICH).

Main Results:

• Thirteen studies included 2,456 patients in the IVT group and 2,411 in the control group.
• IVT significantly improved excellent functional outcome (RR 1.23), good functional outcome (RR 1.15), and reduced disability (OR 1.26).
• IVT increased sICH risk (RR 2.11) but showed similar rates of any ICH and all-cause mortality; no significant subgroup differences were found.

Conclusions:

• Extended-window IVT improves functional outcomes in AIS patients without increasing mortality.
• IVT is supported for selected patients presenting beyond 4.5 hours, despite a higher risk of sICH.