Direct oral anticoagulants versus vitamin K antagonists for the treatment of cerebral venous thrombosis: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND

Current guidelines consider direct oral anticoagulants (DOACs) a reasonable treatment option for cerebral venous thrombosis (CVT), but randomized evidence comparing DOACs vs. vitamin K antagonists (VKAs) remain limited.

OBJECTIVE

To compare the efficacy and safety of DOACs vs. VKAs for CVT treatment.

METHODS

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing DOACs with VKAs in adults with CVT. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through January 2026. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the Peto method. Primary outcomes included recurrent venous thromboembolism (VTE) and intracranial hemorrhage (ICH). Secondary outcomes comprised complete venous recanalization, major bleeding, clinically relevant non-major bleeding (CRNMB), any bleeding, and all-cause mortality.

RESULTS

Of 267 records screened (23 full texts assessed), 6 RCTs (428 patients: DOAC n = 213, VKA n = 215) were included. All studies had some risk of bias. Anticoagulant treatment duration ranged from 3 to 12 months, and follow-up ranged from 6 to 12 months. For recurrent VTE, the OR was 3.14 (95% CI 0.95-10.37). No significant differences between groups emerged for ICH (OR 1.37, 95% CI 0.31-6.16), recanalization, major bleeding, CRNMB, or mortality. Any bleeding risk was significantly lower with DOACs (OR 0.54, 95% CI 0.29-1.00). GRADE certainty was low across all outcomes due to imprecision.

CONCLUSION

These findings suggest comparable efficacy and safety between DOACs and VKAs for CVT but require considerable caution given the small sample size, rare events, wide CIs, and low certainty evidence.