Off-Label NOACs vs. Antiplatelets in AF-Related Stroke with GFR < 15 mL/Min/1.73 m2: A Multicenter Outcome Study

<b>Background:</b> This study aimed to evaluate the efficacy and safety of off-label use of non-vitamin K antagonist oral anticoagulants (NOACs) compared with antiplatelet therapy (APT) in patients with AF-related acute ischemic stroke (AIS) and a glomerular filtration rate (GFR) below 15 mL/min/1.73 m². <b>Methods:</b> We used a multicenter prospective stroke registry to identify patients with AF-related AIS and GFR < 15 mL/min/1.73 m² who were treated with either APT alone or NOAC alone at discharge. Primary outcomes were ischemic stroke recurrence, major bleeding, and all-cause mortality within one year. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. <b>Results:</b> Among 311 eligible patients, 135 (43.4%) received APT and 176 (56.6%) received low-dose NOACs. Compared to APT, NOAC use was associated with a significantly lower risk of ischemic stroke recurrence (aHR 0.54, 95% CI 0.29-0.99) but higher risks of major bleeding (aHR 3.25, 95% CI 1.84-5.73) and all-cause mortality (aHR 2.65, 95% CI 1.60-4.38). The most common causes of death were non-vascular events such as sepsis and respiratory failure. <b>Conclusions:</b> In patients with AF-related stroke and ultra-low GFR, off-label use of NOACs may offer a benefit in stroke prevention but is associated with increased risks of bleeding and mortality. These findings suggest the need for individualized treatment strategies and careful monitoring when prescribing NOACs in this vulnerable population.