Efficacy and Safety of Intravenous Thrombolysis Beyond 4.5 Hours in Ischemic Stroke: A Systematic Review and Meta-Analysis
<b>Background</b>: 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 s...
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2025-07-01
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| author | Muhammad Ahmad Chavin Akalanka Ranasinghe Mais Omar Abu-Sa’da Durga Prasad Bhimineni Muhammed Ameen Noushad Talal Warsi Ahmad Mesmar Munikaverappa Anjanappa Mukesh Sagar K. Patel Gabriel Imbianozor Ali Mustansir Bhatty Ahmad Alareed Quratul Ain Eeshal Zulfiqar Mushood Ahmed Raheel Ahmed |
| author_facet | Muhammad Ahmad Chavin Akalanka Ranasinghe Mais Omar Abu-Sa’da Durga Prasad Bhimineni Muhammed Ameen Noushad Talal Warsi Ahmad Mesmar Munikaverappa Anjanappa Mukesh Sagar K. Patel Gabriel Imbianozor Ali Mustansir Bhatty Ahmad Alareed Quratul Ain Eeshal Zulfiqar Mushood Ahmed Raheel Ahmed |
| author_sort | Muhammad Ahmad |
| collection | DOAJ |
| description | <b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 (<i>p</i> > 0.05). <b>Conclusions</b>: 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. |
| format | Article |
| id | doaj-art-aa3e193b04fa4038ac93c7ae8f9fda3b |
| institution | Matheson Library |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Diagnostics |
| spelling | doaj-art-aa3e193b04fa4038ac93c7ae8f9fda3b2025-07-25T13:19:57ZengMDPI AGDiagnostics2075-44182025-07-011514181210.3390/diagnostics15141812Efficacy and Safety of Intravenous Thrombolysis Beyond 4.5 Hours in Ischemic Stroke: A Systematic Review and Meta-AnalysisMuhammad Ahmad0Chavin Akalanka Ranasinghe1Mais Omar Abu-Sa’da2Durga Prasad Bhimineni3Muhammed Ameen Noushad4Talal Warsi5Ahmad Mesmar6Munikaverappa Anjanappa Mukesh7Sagar K. Patel8Gabriel Imbianozor9Ali Mustansir Bhatty10Ahmad Alareed11Quratul Ain12Eeshal Zulfiqar13Mushood Ahmed14Raheel Ahmed15Junior Clinical Fellow Geriatrics/Acute Medicine, Aneurin Bevan University Healthboard, Caerleon NP18 3XQ, UKDepartment of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, UKRAKCOMs, RAK Medical Health Sciences University, Ras Al Khaimah 11172, United Arab EmiratesCardiology, West Suffolk NHS Foundation Trust, Bury St Edmunds, Suffolk IP33 2QZ, UKNeurology, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, UKCardiology, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, UKCardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi P.O. Box 11001, United Arab EmiratesInternal Medicine, South Tyneside and Sunderland NHS Foundation Trust, Sunderland R4 7TP, UKGujarat Adani Institute of Medical Sciences, Bhuj 370001, Gujarat, IndiaRoyal Wolverhampton NHS Trust, Wolverhampton WV10 0QP, UKHull University Teaching Hospital NHS Trust, Hull HU1 3SA, UKUniversity Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UKDepartment of Medicine, Rotherham General Hospital, Rotherham S60 2UD, UKDepartment of Medicine, Dow University of Health Sciences, Karachi 75280, PakistanDepartment of Medicine, Rawalpindi Medical University, Rawalpindi 46000, PakistanNational Heart & Lung Institute, Imperial College London, London W12 0NN, UK<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 (<i>p</i> > 0.05). <b>Conclusions</b>: 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.https://www.mdpi.com/2075-4418/15/14/1812ischemic strokethrombolysistenecteplasealteplasemeta-analysis |
| spellingShingle | Muhammad Ahmad Chavin Akalanka Ranasinghe Mais Omar Abu-Sa’da Durga Prasad Bhimineni Muhammed Ameen Noushad Talal Warsi Ahmad Mesmar Munikaverappa Anjanappa Mukesh Sagar K. Patel Gabriel Imbianozor Ali Mustansir Bhatty Ahmad Alareed Quratul Ain Eeshal Zulfiqar Mushood Ahmed Raheel Ahmed Efficacy and Safety of Intravenous Thrombolysis Beyond 4.5 Hours in Ischemic Stroke: A Systematic Review and Meta-Analysis Diagnostics ischemic stroke thrombolysis tenecteplase alteplase meta-analysis |
| title | Efficacy and Safety of Intravenous Thrombolysis Beyond 4.5 Hours in Ischemic Stroke: A Systematic Review and Meta-Analysis |
| title_full | Efficacy and Safety of Intravenous Thrombolysis Beyond 4.5 Hours in Ischemic Stroke: A Systematic Review and Meta-Analysis |
| title_fullStr | Efficacy and Safety of Intravenous Thrombolysis Beyond 4.5 Hours in Ischemic Stroke: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | Efficacy and Safety of Intravenous Thrombolysis Beyond 4.5 Hours in Ischemic Stroke: A Systematic Review and Meta-Analysis |
| title_short | Efficacy and Safety of Intravenous Thrombolysis Beyond 4.5 Hours in Ischemic Stroke: A Systematic Review and Meta-Analysis |
| title_sort | efficacy and safety of intravenous thrombolysis beyond 4 5 hours in ischemic stroke a systematic review and meta analysis |
| topic | ischemic stroke thrombolysis tenecteplase alteplase meta-analysis |
| url | https://www.mdpi.com/2075-4418/15/14/1812 |
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