CT perfusion-guided thrombolysis in the extended window: from trial eligibility to individualized patient selection

Recent randomized controlled trials (RCTs) have expanded the role of intravenous thrombolysis (IVT) into the extended time window (beyond 4.5 h) using CT perfusion (CTP)-based patient selection. Following the inclusion of extended-window thrombolysis into the most recent edition of the American Heart Association Acute Ischemic Stroke Guidelines in 2026, these recently completed studies, EXTEND, HOPE, TRACE III, and OPTION, collectively must now inform the rapid clinical implementation of this treatment as we enter an age of precision medicine in the management of acute stroke. This mini-review seeks to address three core implementation challenges for patient selection when considering extended-window thrombolysis: (1) efforts to establish clinical pathways for patient selection should consider the phenotype of patients enrolled in extended-window thrombolysis RCTs in addition to enrollment criteria, (2) assessments of the safety of extended-window thrombolysis based on the best available evidence are reassuring, and (3) promising results from extended-window thrombolysis trials for distal and medium vessel occlusion (DMeVO) stroke patients, in concert with recent neutral endovascular therapy (EVT) trials for treating DMeVO stroke, have carved out a distinct role for IVT in this patient population. Herein, we aim to leverage the best available evidence to address these critical questions that vascular neurologists face as we work toward the clinical implementation of this trial evidence.