BACKGROUND: Cerebral venous thrombosis (CVT), a rare stroke variant, poses treatment challenges, especially in young individuals. While guidelines recommend heparin followed by warfarin, warfarin has limitations. Direct oral anticoagulants (DOACs) offer a potential alternative, but evidence on their use in CVT management is limited. The TriNetX study aimed to provide real-world insights into DOAC efficacy and safety for CVT. METHODS: We conducted a retrospective cohort study utilizing data from TriNetX to identify patients with CVT. Propensity score matching (PSM) was used to balance the covariates between patients receiving DOACs and those receiving warfarin. The primary outcome was recurrent CVT, with secondary outcomes including intracerebral hemorrhage and all-cause mortality. RESULTS: Among 1,507 patients with CVT, PSM generated 551 matched individuals in both the study and control groups. The study group that received DOACs exhibited a lower risk of CVT recurrence (Hazard Ratio [HR], 0.77
95% Confidence Interval [CI], 0.628-0.97) and a higher 360-day event-free survival rate (p <
0.001). Subgroup analyses revealed significantly reduced recurrent CVT risk in the study group, particularly among females (HR, 0.67
95% CI, 0.50-0.89), individuals aged 41-64 years (HR, 0.52
95% CI, 0.35-0.75), and patients with normal weight (HR, 0.65
95% CI, 0.50-0.84). Moreover, recipients of DOACs had a lower risk of intracerebral hemorrhage (HR, 0.62
95% CI, 0.43-0.91) and comparable all-cause mortality (HR, 1.03
95% CI, 0.67-1.59). CONCLUSIONS: This study underscores the potential of DOACs as a promising treatment for CVT, demonstrating reduced recurrence and intracerebral hemorrhage risks with comparable all-cause mortality.