Comparison of DOAC Versus VKA for Cerebral Venous Thrombosis: A Systematic Review and Meta-Analysis

BACKGROUND: Cerebral venous thrombosis is an uncommon cause of stroke that primarily affects young adults. Several clinical trials and observational studies have compared vitamin K antagonists (VKAs) with direct oral anticoagulants (DOACs) for treating cerebral venous thrombosis, but the small sample sizes limit the ability to draw firm conclusions. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials and observational studies comparing DOACs with VKAs for the treatment of cerebral venous thrombosis. Studies published between January 2007 and July 2025 were included. Prespecified subgroup analyses were conducted by study design, DOAC class (anti–factor Xa inhibitors versus direct thrombin inhibitors), and VKA. Risk of bias was assessed using the Cochrane Risk-of-Bias Tool 2 for randomized trials and the Risk of Bias in Nonrandomized Studies of Interventions for observational studies. Pooled risk ratios (RRs) with 95% CIs were calculated using random-effects models. RESULTS: Fourteen studies (8 randomized clinical trials [RCTs] and 6 observational studies) were included. Among 3698 patients, 1669 (45.1%) received DOACs and 2029 (54.9%) received VKAs. Rates of recurrent venous thromboembolism (10.24% versus 10.99%), major bleeding (4.26% versus 6.18%), clinically relevant nonmajor bleeding (2.63% versus 1.66%), good functional outcomes (95.09% versus 89.25%), and mortality (3.37% versus 3.30%) were similar in DOACs and VKAs. Recurrent venous thromboembolism was similar between DOACs and VKAs in RCTs (RR, 1.06 [95% CI, 0.35–3.24]) and in the overall pooled analysis of all studies (RR, 0.92 [95% CI, 0.55–1.53]). Major bleeding did not differ between DOACs and VKAs in RCTs (RR, 0.73 [95% CI, 0.24–2.22]) or in the overall analysis (RR, 0.74 [95% CI, 0.44–1.25]; P =0.26). Clinically relevant nonmajor bleeding was also comparable in RCTs (RR, 1.06 [95% CI, 0.25–4.48]) and overall (RR, 1.22 [95% CI, 0.38–3.86]). Good functional outcomes (modified Rankin Scale score of 0–2) were similar between DOACs and VKAs in RCTs (RR, 1.00 [95% CI, 0.84–1.19]) and in the combined analysis of all studies (RR, 1.02 [95% CI, 0.93–1.11]). Mortality was similar between DOACs and VKAs in RCTs (RR, 1.15 [95% CI, 0.28–4.68]) and in the pooled analysis. When direct thrombin inhibitors were compared with factor Xa inhibitors, there were no significant differences in outcomes. CONCLUSIONS: DOACs demonstrated comparable efficacy and safety to VKAs in the treatment of cerebral venous thrombosis. These findings support the use of DOACs as a reasonable alternative.