Intravenous thrombolysis in acute ischemic stroke after recent direct oral anticoagulant intake: toward evidence-informed care

The use of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with recent direct oral anticoagulant (DOAC) intake remains one of the most debated issues in contemporary stroke medicine. Current international guidelines generally discourage IVT within 48 h of DOAC ingestion, largely because of concerns regarding symptomatic intracranial hemorrhage (sICH) and the absence of randomized evidence. However, an increasing body of evidence from international registries and multicenter cohorts has not identified a clear increase in sICH among carefully selected patients with recent DOAC exposure who received IVT. Some observational studies have also reported an association with more favorable functional outcomes than those observed in otherwise eligible patients in whom reperfusion therapy was withheld, although these comparisons are susceptible to selection bias and confounding by indication. In this Perspective, we discuss recent advances that have challenged the traditional practice of broadly excluding patients with recent DOAC exposure from IVT. We review observational evidence concerning IVT in selected patients, examine biological hypotheses that could be relevant to the observed clinical findings, and discuss evolving roles of reversal agents and laboratory assessment of anticoagulant activity. We further highlight current implementation barriers and future research priorities, including prospective studies, improved point-of-care anticoagulant testing, and refinement of patient-selection strategies. We argue that contemporary evidence supports reconsideration of rigid time-based exclusion criteria in favor of more individualized, evidence-informed decision-making. Although important uncertainties remain, recent DOAC exposure may not necessarily preclude IVT in appropriately selected patients, particularly when anticoagulant activity can be reliably assessed.