Efficacy and safety of intravenous thrombolysis beyond 4.5 hours in ischemic stroke: a systematic review and meta-analysis
Ahmad, Muhammad Ranasinghe, Chavin Akalanka Abu-Sa'da, Mais Omar Bhimineni, Durga Prasad Noushad, Muhammed Ameen Warsi, Talal Mesmar, Ahmad Mukesh, Munikaverappa Anjanappa Patel, Sagar K Imbianozor, Gabriel
Ahmad, Muhammad
Ranasinghe, Chavin Akalanka
Abu-Sa'da, Mais Omar
Bhimineni, Durga Prasad
Noushad, Muhammed Ameen
Warsi, Talal
Mesmar, Ahmad
Mukesh, Munikaverappa Anjanappa
Patel, Sagar K
Imbianozor, Gabriel
Affiliation
Aneurin Bevan University Healthboard; University Hospitals Birmingham NHS Foundation Trust; RAK Medical Health Sciences University; West Suffolk NHS Foundation Trust; University Hospitals Plymouth NHS Trust; Sheikh Shakhbout Medical City; South Tyneside and Sunderland NHS Foundation Trust; Gujarat Adani Institute of Medical Sciences; Royal Wolverhampton NHS Trust; Hull University Teaching Hospital NHS Trust; University Hospital Southampton NHS Foundation Trust; Rotherham General Hospital; Dow University of Health Sciences; Rawalpindi Medical University; Imperial College London; Royal Brompton Hospital
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Publication date
2025-07-18
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Abstract
Background: Intravenous thrombolysis (IVT) is the standard treatment for ischemic stroke within 4.5 h of symptom onset. However, a significant proportion of patients present beyond this window. This study aims to evaluate the efficacy and safety of IVT beyond the 4.5 h window in selected patients.
Methods: A systematic literature search was conducted across PubMed, Cochrane Library, and Google Scholar from inception to April 2025. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model.
Results: A total of 12 RCTs were included, with 3236 patients. Compared to controls, IVT significantly improved excellent functional outcomes [OR: 1.40; 95% CI: 1.21-1.62] and good functional outcomes [OR: 1.26; 95% CI: 1.06-1.50] at 90 days. IVT also improved recanalization [OR: 2.47; 95% CI: 1.96-3.12], reperfusion [OR: 2.20; 95% CI: 1.26-3.84], and early neurological improvement [OR: 1.91; 95% CI: 1.12-3.26]. However, it was associated with a significantly higher risk of symptomatic intracranial hemorrhage (sICH) [OR: 2.17; 95% CI: 1.25-3.79], any ICH [OR: 1.49; 95% CI: 1.09-2.04], and type-II parenchymal hemorrhage (PH) [OR: 2.14; 95% CI: 1.19-3.83]. No significant difference was observed in systemic hemorrhage, 90-day all-cause mortality, 7-day mortality, or 90-day intervention-related mortality (p > 0.05).
Conclusions: IVT beyond 4.5 h improves neurological outcomes in patients with ischemic stroke without increasing overall mortality or systemic bleeding, though it raises the risk of sICH, any ICH, and type-II PH. Further large RCTs are needed to confirm these findings and guide clinical practice.
Citation
Ahmad M, Ranasinghe CA, Abu-Sa'da MO, Bhimineni DP, Noushad MA, Warsi T, Mesmar A, Mukesh MA, Patel SK, Imbianozor G, Bhatty AM, Alareed A, Ain Q, Zulfiqar E, Ahmed M, Ahmed R. Efficacy and Safety of Intravenous Thrombolysis Beyond 4.5 Hours in Ischemic Stroke: A Systematic Review and Meta-Analysis. Diagnostics (Basel). 2025 Jul 18;15(14):1812. doi: 10.3390/diagnostics15141812.
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Article