Initial Direct Oral Anticoagulants Versus Warfarin After Cerebral Venous Thrombosis: A Target Trial Emulation

BACKGROUND: Vitamin K antagonists have traditionally been used after cerebral venous thrombosis, whereas direct oral anticoagulants (DOACs) are increasingly prescribed. Whether DOACs are noninferior to warfarin for preventing 1-year symptomatic recurrent venous thromboembolism (VTE) remains uncertain. METHODS: We conducted a registry-based target trial emulation in a bidirectional multicenter Chinese cerebral venous thrombosis registry (retrospective phase, 2015–2022; prospective phase, 2023–2025). Eligible patients were adults with imaging-confirmed cerebral venous thrombosis who initiated either a DOAC or warfarin within 30 days after diagnosis. Time zero was the date of the first oral anticoagulant prescription. The primary efficacy outcome was symptomatic recurrent VTE within 1 year. Propensity score overlap weighting was used, and weighted Fine-Gray models treated death as a competing event. The clinically acceptable noninferiority margin was defined as an absolute increase of 1.5 percentage points in 1-year recurrent VTE risk, corresponding approximately to a relative margin of 1.50 for the primary Fine-Gray analysis. RESULTS: Among 2476 eligible patients, 942 initiated a DOAC (rivaroxaban, n=701; dabigatran, n=121; apixaban, n=113; edoxaban, n=7) and 1534 initiated warfarin. Within 1 year, symptomatic recurrent VTE occurred in 36 and 73 patients, respectively. The overlap-weighted 1-year recurrence risks were 3.74% and 5.47%, corresponding to a risk difference of −1.73 percentage points (95% CI, −3.76 to 0.30). DOAC treatment was associated with a lower subdistribution hazard ratio of 0.67 compared with that of warfarin ([95% CI, 0.37–1.21]; P =0.184), meeting the prespecified noninferiority criterion ( P for noninferiority=0.004). Major bleeding was rare within 1 year (0 versus 1 patient). Clinical nonmajor bleeding occurred in 18 versus 34 patients, and any bleeding occurred in 48 versus 75 patients. CONCLUSIONS: Among patients with cerebral venous thrombosis selected for oral anticoagulation, initial treatment with a DOAC met the noninferiority criterion relative to warfarin for the prevention of symptomatic recurrent VTE at 1 year. Findings regarding bleeding outcomes were exploratory and do not permit conclusions regarding comparative safety or equivalence.