Exploring Between-Study Heterogeneity in Extended-Window IV Thrombolysis for Acute Ischemic Stroke: A Meta-Analysis...

Area of Science:

• Neurology
• Stroke Medicine
• Clinical Trials

Background:

• Intravenous thrombolysis (IVT) is standard for acute ischemic stroke (AIS) within 4.5 hours.
• Evidence supports IVT use in extended time windows (4.5-24 hours) for selected patients.
• Systematic review and meta-analysis to evaluate IVT efficacy and safety beyond 4.5 hours.

Purpose of the Study:

• Evaluate the effectiveness and safety of IVT in AIS patients presenting 4.5-24 hours after symptom onset.
• Explore factors contributing to heterogeneity in studies of extended-window IVT.
• Provide evidence for expanded IVT recommendations in specific patient populations.

Main Methods:

• Systematic search of MEDLINE, Cochrane Library, and ClinicalTrials.gov.
• Included randomized controlled trials (RCTs) or individual patient-data meta-analyses of RCTs.
• Primary outcome: excellent functional recovery (mRS 0-1 at 90 days); secondary outcomes: functional independence, disability reduction, mortality, and symptomatic intracranial hemorrhage (sICH).
• Multivariable meta-regression analyzed thrombolytic agent, thrombectomy, and territory.

Main Results:

• IVT significantly improved excellent functional outcome (mRS 0-1; 40.3% vs 33.2%) and functional independence (mRS 0-2; 54.5% vs 50.1%).
• IVT was associated with greater odds of reduced disability (common OR 1.18).
• IVT increased sICH risk (3.2% vs 1.4%) but did not significantly increase 90-day mortality (13.7% vs 13.0%).
• Endovascular thrombectomy was the primary driver of between-study heterogeneity.

Conclusions:

• Extended-window IVT (4.5-24 hours) enhances functional outcomes in AIS patients with salvageable tissue.
• IVT provides a critical reperfusion strategy for patients lacking timely thrombectomy access.
• This study offers Class I evidence supporting IVT use in moderate-to-severe AIS within 4.5-24 hours when thrombectomy is unavailable.