Direct Oral Anticoagulants for Cerebral Venous Thrombosis: Equivalent Efficacy, Superior Safety Compared to Vitamin K Antagonists
Mohammad Munim Zahoor1, Muhammad Talha Maqsood2, Ahsan Abid3, Nabeeha Noor3, Ezza Bashir4, Huda Memon5, David Ermak1
1Neurology, Geisinger, 2King Edward Medical University, 3Sahiwal Medical College and Teaching Hospital, 4Akhtar Saeed Medical and Dental College, 5Rutgers University
Objective:
To perform the largest systematic review and meta-analysis comparing DOACs and VKAs in CVT, evaluating efficacy, safety, and treatment durability to date.
Background:
The optimal anticoagulant for cerebral venous thrombosis (CVT) remains debated. Direct oral anticoagulants (DOACs) are increasingly favored over vitamin K antagonists (VKAs), but their comparative efficacy and safety remain uncertain.
Design/Methods:
We systematically searched PubMed, Embase, Cochrane Central, Scopus, and ClinicalTrials.gov from inception to August 2025. Eligible randomized controlled trials (RCTs) and observational studies comparing DOACs with VKAs in CVT were included. Outcomes assessed included recurrence, mortality, bleeding events, recanalization, and treatment discontinuation. Data were pooled using a random-effects model (R, version 4.5.1). Risk of bias was assessed using ROB 2.0 for RCTs and ROBINS-I for observational studies.
Results:
Twenty studies (5 RCTs, 15 observational cohorts) comprising 5,529 patients were analyzed. Mean age was ~42 years; average anticoagulation duration was 6 months. Risk factors included oral contraceptive use, thrombophilia, malignancy, infection, trauma, and postpartum state. DOACs were associated with a significantly lower risk of major bleeding compared with VKAs (RR 0.69, 95% CI 0.51–0.94) while maintaining similar efficacy for CVT recurrence (RR 0.84, 95% CI 0.70–1.00) and mortality (RR 0.96, 95% CI 0.67–1.37). Minor bleeding (RR 1.00, 95% CI 0.47–2.14), treatment discontinuation (RR 1.31, 95% CI 0.58–2.92, I2= 38.6%, τ²= 0.246), and recanalization (RR 1.00, 95% CI 0.96–1.04, I2= 2.3%, τ²= 0.0001) did not differ significantly between groups. Findings were consistent across RCTs and observational studies, with minimal heterogeneity.
Conclusions:
This meta-analysis—the largest to date in CVT—demonstrates that DOACs provide efficacy equivalent to VKAs with a superior safety profile. DOACs offer equivalent efficacy with a superior safety profile compared to VKAs, supporting their use as a preferred therapeutic strategy in appropriately selected patients and informing future guideline recommendations.
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