Thrombolysis for ischemic stroke at 4.5 to 24 hours: An updated meta-analysis of randomized controlled trials

Only a minority of stroke patients are eligible for intravenous thrombolysis (IVT) within the standard 4.5-hour window. The safety and efficacy of IVT beyond this time frame remain insufficiently researched.

To evaluate the efficacy and safety following IVT in patients with AIS (4.5-24 hours).

The systematic review was registered in PROSPERO (CRD420251019740). Inclusion criteria included randomized clinical trials that examined outcomes, mortality, and complications in patients with AIS comparing IVT vs Best Medical Treatment (BMT). The risk of bias in the included studies was evaluated using the revised tool for assessing risk of bias. Meta-analyses assessed efficacy (excellent outcomes, functional independence) and safety (symptomatic intracranial hemorrhage [sICH], mortality) using a random-effects model.

A total of six randomized clinical trials with 1884 initially enrolled patients were included in the analysis. Higher excellent outcome rates were observed in the IVT group (RR, 1.25; 95 % CI, 1.11-1.41). No significant differences were found in functional independence (RR, 1.14; 95 % CI, 0.98-1.32), sICH (RR, 1.91; 95 % CI, 0.85-4.33), or 90-day all-cause mortality (RR, 1.02; 95 % CI, 0.81-1.29). There was considerable heterogeneity among the studies included in the functional independence outcome (I² = 40.8 %, τ² = 0.01); however, no heterogeneity was observed for other outcomes (I² = 0, τ² = 0).

These findings suggest that IVT with tenecteplase or alteplase may enhance 90-day excellent outcomes in patients with late-window acute ischemic stroke without significantly increasing the risk of sICH or mortality.