Late-window reperfusion in imaging-selected ischemic stroke: interpreting thrombolysis and mechanical thrombectomy...

Mechanical thrombectomy (MT) is superior to medical therapy for anterior circulation proximal large-vessel occlusion (LVO) stroke, including in imaging-selected patients treated 6 to 24 h after their last known well (LKW) time. Beyond 4.5 h, the role of intravenous thrombolysis (IVT) has become more relevant because many health systems lack the ability to provide timely thrombectomy access for eligible late-window patients. Recent late-window IVT trials, including TRACE-III and HOPE, have demonstrated benefit in imaging-selected patients in whom thrombectomy was not planned or not effectively deliverable, addressing a critical systems-of-care gap. We review these trials alongside emerging evidence and situate each within a systems-of-care framework, distinguishing bridging scenarios from settings where MT is unavailable or substantially delayed. However, we argue that their results should not be taken to imply therapeutic equivalence with MT, a comparison that is misleading on methodological grounds. No randomized, head-to-head late-window trial of IVT versus MT exists. Comparing treated-arm outcomes across these separate trials as a proxy for therapeutic equivalence is vulnerable to differences in baseline prognosis, occlusion site, imaging selection, access to rescue therapy, and control-group outcomes. In this Perspective, we argue that these trials should be read one at a time. Each treated arm should be judged against its own control group and against the clinical and angiographic profile of the patients enrolled, not against treated arms from trials that enrolled very different strokes.