Extending the Treatment Window for Intravenous Thrombolysis in Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis Publisher

Summary: Can clot-busting drugs help stroke patients after 4.5 hours? A review found imaging-selected treatment improved outcomes but increased brain bleeding risk. #Stroke #Thrombolysis

Rahmati S ; Alinejadfard M ; Zarinfar Y ; Moradi A ; Ghabousian A ; Najafi K ; Iskander F ; Latib A ; Kuno T ; Ramchand P ; Hosseini K
Source: Neurology: Clinical Practice Published:2026

Abstract

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 – Fourteen studies involving 4, 944 patients were included. The mean age was 69.8 years, 58.2% were male, the median National Institutes of Health Stroke Scale score was 9, and 12.3% received preplanned endovascular thrombectomy (EVT). A total of 2, 492 patients received IVT in an extended time window (4.5–24 hours). Compared with standard care, extended IVT was associated with higher odds of achieving an excellent functional outcome (OR: 1.43 [95% CI 1.25–1.63]), a good functional outcome (OR: 1.25 [95% CI 1.11–1.40]), and recanalization (OR: 3.28 [95% CI 2.09–5.16]). There was no difference in 3-month mortality (OR: 1.21 [95% CI 0.95–1.53]). However, IVT increased the risk of sICH (OR: 2.51 [95% CI 1.47–4.28]). Sensitivity analysis excluding patients who received EVT showed no impact on the outcomes. TNK exhibited similar efficacy to alteplase but showed potentially lower odds of sICH (OR: 1.96, 95% CI 1.06–3.64) compared with alteplase (OR: 5.29, 95% CI 1.80–15.57); however, the subgroup difference was not significant (p = 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. © 2026 American Academy of Neurology