Safety and Efficacy of Intravenous Thrombolysis after DOAC Use in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis in Light of Current Guidelines

Background Current guidelines recommend avoiding intravenous thrombolysis (IVT) in patients receiving direct oral anticoagulants (DOACs) because of concerns regarding intracranial hemorrhage (ICH). However, emerging evidence has reported inconsistent findings regarding the safety and efficacy of IVT in this population. We aimed to reassess the safety and clinical outcomes of IVT in patients with acute ischemic stroke (AIS) receiving DOAC therapy. Methods Four databases (PubMed, Scopus, Web of Science, and the Cochrane Library) were systematically searched to identify comparative studies evaluating intravenous thrombolysis in patients with acute ischemic stroke receiving DOACs. The primary outcomes included symptomatic intracranial hemorrhage (sICH), mortality, and favorable functional outcome defined as a modified Rankin Scale (mRS) score of 0–2. Secondary outcomes included any ICH and major extracranial bleeding. Random-effects meta-analyses were performed using RevMan Web. Results Eleven studies involving 262,325 patients were included, of whom 9,497 received DOAC therapy prior to IVT. The pooled analysis demonstrated no significant difference between DOAC-treated and non-anticoagulated patients regarding symptomatic intracranial hemorrhage (sICH) (RR = 1.01, 95% CI: 0.79–1.29), any intracranial hemorrhage (ICH) (RR = 1.47, 95% CI: 0.77–2.83), or mortality (RR = 0.63, 95% CI: 0.32–1.23). Patients receiving DOACs demonstrated a significantly higher likelihood of achieving favorable functional outcomes (mRS 0–2) at 3 months (RR = 2.43, 95% CI: 1.51–3.89). However, major extracranial bleeding was significantly more frequent in the DOAC group (RR = 1.62, 95% CI: 1.18–2.21). Conclusion This meta-analysis suggests that IVT in carefully selected patients with recent DOAC exposure may not be associated with a substantial increase in intracranial hemorrhage or mortality. Nevertheless, given the observational nature of the available evidence and the possibility of residual confounding, these findings should be interpreted cautiously. Further prospective studies are needed to better define the safety and efficacy of IVT in DOAC-treated patients.