The study focuses on a critical clinical question: whether IVT given beyond the traditional 4.5-hour window could still offer benefit to patients with large vessel occlusion (LVO) strokes who first arrive at primary stroke centers (PSCs) and require transfer to comprehensive stroke centers (CSCs) for thrombectomy. Earlier trials, including TIMELESS, reported no clear advantage of late-window IVT in patients directly presenting to CSCs. However, the current investigation examined a different scenario—patients facing longer delays before thrombectomy, giving thrombolytic therapy more time to act.
Researchers analyzed data from 584 consecutive patients with LVO strokes admitted to 20 French PSCs between January 2020 and December 2024. All patients arrived more than 4.5 hours after they were last known well, and all were subsequently transferred to CSCs for EVT. Of these, 232 patients (39.7%) received IVT before transfer. The median age was 71 years, and the baseline stroke severity score indicated moderate to severe stroke.
The key findings of the study were as follows:
- The investigators used propensity score overlap weighting to balance clinical and imaging characteristics between groups.
- IVT use was independently linked to better functional recovery at three months.
- Patients who received IVT had nearly twice the odds of achieving improved outcomes on the modified Rankin Scale compared with those who did not undergo thrombolysis (common OR 1.97).
- Recanalization rates during transfer were significantly higher among patients who received IVT.
- Those given IVT were far more likely to arrive at the CSC with reopened vessels (OR 8.69).
- No differences were noted in safety outcomes, including symptomatic intracerebral hemorrhage, helping alleviate concerns about bleeding risks with late-window thrombolysis.
The authors caution that the observational nature of the study limits causal conclusions. IVT decisions relied heavily on advanced imaging, particularly DWI-FLAIR mismatch, which may have introduced selection bias. While statistical adjustments minimized group differences, unmeasured confounders may still exist. They also note that smaller subgroup sizes restrict generalizability, especially for patients presenting very late, those with specific occlusion sites, or those assessed using CT-only imaging.
Despite these limitations, the results highlight a promising therapeutic approach for stroke systems of care—particularly in regions where transfer delays are unavoidable. The findings provide compelling support for conducting randomized clinical trials to confirm whether late-window thrombolysis should be incorporated into transfer protocols for thrombectomy candidates.
"If validated, this strategy could significantly improve outcomes for a large population of stroke patients who currently fall outside the conventional treatment window," the authors concluded.
Reference:
Seners P, Nehme N, Ter Schiphorst A, et al. Intravenous Thrombolysis Use in the Late Time Window Before Interhospital Transfer for Thrombectomy. JAMA Neurol. Published online December 01, 2025. doi:10.1001/jamaneurol.2025.4712
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