Title: Comparing the Efficacy and Safety of Intravenous Thrombolytics in Ischemic Stroke Beyond the 4.5- Hour Time Window: A Systematic Review and Meta-analysis of Randomized Controlled Trials (P6-4.016)
Authors: Zain ul Abideen, Hassan Waseem, Dua Ghori, Faizan Shahzad, Shamama Kaleem, Misha Ahmed, Muhammad Ansari, Muhammad Ansari, Rowaid Ahmad, Justin Chen, Jamir Pitton Rissardo, Ana Leticia Fornari Caprara, Vishnu Byroju, Brandon Lucke-Wold, and Adam Dmytriw
Conference: 2026 AAN, Chicago, IL
Objective
This meta-analysis aims to evaluate the efficacy and safety of intravenous thrombolytics (IVTs) in ischemic stroke beyond the 4.5-hour window.
Background
Stroke significantly affects global health, and IVTs like tenecteplase and alteplase are highly time-dependent. Although they show potential beyond 4.5 hours, the evidence remains inconclusive.
Design/Methods
PubMed, Cochrane Central, and ScienceDirect were searched through August 2025. The risk ratios (RRs) were pooled with 95% confidence intervals under the random effects model using Review Manager version 5.4.1. The quality assessment was done using the Cochrane Risk of Bias (RoB) 2.0 tool. An excellent functional outcome is defined as a modified Rankin Scale (mRS) score of 0–1. A good functional outcome is defined as an mRS of 0–2.
Results
Thirteen randomized controlled trials involving a total of 3,602 patients were analyzed. Compared to the control group, IVT significantly improved the rates of excellent (RR= 1.22; 95%CI: [1.13, 1.31];p <0.00001; I2 = 0%) and good (RR= 1.11; 95%CI: [1.06, 1.18];p <0.0001; I2 = 0%) functional outcomes. However, the risk of symptomatic (RR= 2.28; 95%CI:[1.35, 3.85];p = 0.002; I2 = 0%) and any (RR= 1.22; 95%CI:[1.01, 1.46];p = 0.04; I2 = 13%) intracranial hemorrhage (ICH) was also higher with IVT; mortality rates, however, showed no significant difference (RR= 1.10; 95%CI:[0.89, 1.36];p = 0.35). Tenecteplase at 0.25 mg/kg did not improve functional outcomes or increase the risk of ICH. Similarly, low-dose 0.60 mg/kg alteplase did not significantly enhance functional outcomes or raise the risk of ICH, while alteplase at 0.90 mg/kg showed results consistent with the overall IVT group.
Conclusions
IVT significantly improved the functional outcomes (excellent and good) but increased the risk of ICH (symptomatic and any) with comparable mortality, primarily in the alteplase 0.90 mg/kg subgroup. However, the 0.25 mg/kg tenecteplase and 0.60 mg/kg low-dose alteplase showed no increase in functional or hemorrhagic outcomes.
Citation
ul Abideen Z, Waseem H, Ghori D, Shahzad F, Kaleem S, Ahmed M, Ansari M, Ansari M, Ahmad R, Chen J, Rissardo JP, Caprara AL, Byroju V, Lucke-Wold B, Dmytriw A. Comparing the Efficacy and Safety of Intravenous Thrombolytics in Ischemic Stroke Beyond the 4.5- Hour Time Window: A Systematic Review and Meta-analysis of Randomized Controlled Trials (P6-4.016). Neurology 2026;106(11_suppl_1):518. doi: 10.1212/WNL.0000000000212969.
Figure 1. Forest plots of randomized trials show IV thrombolysis beyond 4.5 hours improves excellent and good functional outcomes versus control, with low heterogeneity across studies.