Direct oral anticoagulants versus vitamin K antagonist-based standard care in cerebral venous thrombosis: a systematic review and meta-analysis of randomized controlled trials

Cerebral venous thrombosis (CVT) is an uncommon form of stroke that predominantly affects younger adults. Anticoagulation remains the cornerstone of treatment. Direct oral anticoagulants (DOACs) offer practical advantages over vitamin K antagonists (VKAs), but controlled-trial evidence remains limited. To evaluate the efficacy and safety of DOACs compared with VKA-based standard care in patients with CVT. We conducted a systematic review and random-effects meta-analysis of eligible controlled trials reported by their investigators as randomized. The primary efficacy outcome was radiological recanalization or improvement at approximately 6 months, and the primary safety outcome was major bleeding. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. Secondary clinical outcomes were summarized narratively. A post hoc sensitivity analysis excluded the trial with predictable date-based allocation. Six eligible trials enrolled 430 participants; outcome analyses included up to 428 participants. Three trials with 229 evaluable participants contributed to the radiological recanalization or improvement meta-analysis, which showed no statistically significant difference (RR 0.94; 95% CI 0.81-1.09; I-squared = 0%). Excluding Maqsood et al., which used predictable allocation by admission date and was judged high risk for the randomization process, yielded a similar estimate (RR 0.90; 95% CI 0.75-1.08; I-squared = 0%). Three informative trials contributed to the relative-effect analysis for major bleeding (RR 0.60; 95% CI 0.12-3.00; I-squared = 0%); two additional trials reported no major bleeding in either group and were not estimable. Across the five trials reporting a harmonizable major-bleeding outcome, major bleeding occurred in 2 of 188 DOAC-treated participants and 4 of 190 comparator-treated participants. Other clinical events were sparse and heterogeneous. Available controlled-trial evidence did not demonstrate statistically significant differences between DOACs and VKA-based standard care for radiological recanalization or improvement or major bleeding. The estimates remain imprecise because of small trials, sparse events, and heterogeneous radiological outcome definitions. Larger, adequately powered trials are required.