Ahmad, MuhammadRanasinghe, Chavin AkalankaAbu-Sa'da, Mais OmarBhimineni, Durga PrasadNoushad, Muhammed AmeenWarsi, TalalMesmar, AhmadMukesh, Munikaverappa AnjanappaPatel, Sagar KImbianozor, GabrielBhatty, Ali MustansirAlareed, AhmadAin, QuratulZulfiqar, EeshalAhmed, MushoodAhmed, Raheel2025-08-062025-08-062025-07-18Ahmad 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/diagnostics15141812.2075-441810.3390/diagnostics1514181240722561diagnostics1514181240722561https://westmid.openrepository.com/handle/20.500.14200/8146Background: 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.enNeurology::StrokeNeurologyArticle