Extending the Treatment Window for Intravenous Thrombolysis in Acute Ischemic Stroke
BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke within 4.5 hours of onset. However, imaging-based selection may extend the treatment window. This systematic review and meta-analysis evaluated the efficacy and safety of IVT administered beyond 4.5 hours after stroke onset or last known well (LKW) in patients selected based on imaging findings. METHODS: A comprehensive search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials comparing IVT with alteplase or tenecteplase (TNK) administered >4.5 hours after stroke onset/LKW vs standard care. Primary outcomes were 3-month excellent (modified Rankin Scale [mRS] 0-1) functional outcome and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included good (mRS 0-2) functional outcome, recanalization, and 3-month mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis assessed differences between alteplase and TNK. RESULTS: = 0.11). DISCUSSION: Among patients selected based on imaging, 4.5-24 hours after stroke onset/LKW, IVT improves outcomes despite an increased risk of sICH. TNK showed similar efficacy to alteplase, with a possible lower risk of sICH; however, direct comparisons in future trials are needed.
Authors
- Fady Iskander (ORCID: https://orcid.org/0000-0002-8653-2918)
- Kimia Najafi (ORCID: https://orcid.org/0000-0002-0951-9779)
- Amir Ghabousian (ORCID: https://orcid.org/0000-0002-4176-6972)
- Kaveh Hosseini (ORCID: https://orcid.org/0000-0001-5676-3099)
- Amir Moradi (ORCID: https://orcid.org/0000-0002-7307-8787)
- Preethi Ramchand
- Azeem Latib (ORCID: https://orcid.org/0000-0001-9035-343X)
- Soheil Rahmati (ORCID: https://orcid.org/0009-0008-2302-8918)
- Toshiki Kuno (ORCID: https://orcid.org/0000-0002-2487-8366)
- Yasaman Zarinfar (ORCID: https://orcid.org/0000-0002-3559-6022)
- Ali Moradi (ORCID: https://orcid.org/0000-0003-1620-430X)
- Mohammadreza Alinejadfard
Institutions
- University of Copenhagen (DK)
- Montefiore Medical Center (US)
- Thomas Jefferson University (US)
- University of South Florida (US)
- MedStar Union Memorial Hospital (US)
- Gentofte Hospital (DK)
- Massachusetts General Hospital (US)
- National Institute of Genetic Engineering and Biotechnology (IR)
- Tehran University of Medical Sciences (IR)
Publication Details
- Journal
- Neurology Clinical Practice
- Published
- 2026-09-11
- DOI
- https://doi.org/10.1212/cpj.0000000000200654
- Citations
- 1
- Primary Topic
- Acute Ischemic Stroke Management
- Type
- article
- Field-Weighted Citation Impact
- 5.62