Anticoagulation
Corey Diamond, PharmD
Comparing outcomes between direct oral anticoagulant (DOAC) and vitamin K antagonist users across a large, multinational cohort, researchers found no significant differences in rates of major bleeding or recurrent thrombosis.
The results, published in the March 2025 issue of The Lancet Neurology, support DOACs as a reasonable alternative to vitamin K antagonists in the treatment of cerebral venous thrombosis (CVT).
CVT represents a rare stroke subtype that often affects younger adults, particularly women. Clinicians usually treat CVT with heparin followed by long-term anticoagulation using a vitamin K antagonist like warfarin. However, DOACs have gained popularity due to their ease of use and lack of routine monitoring requirements. But how do DOACs and vitamin K antagonists for CVT really compare?
Design
The DOAC-CVT study followed 619 adults with radiologically confirmed CVT who began treatment with either a DOAC or a vitamin K antagonist within 30 days of diagnosis. The research team enrolled participants from 65 hospitals across 23 countries between January 2021 and January 2024. They excluded patients who had used anticoagulants before diagnosis or who had absolute contraindications to DOACs, such as pregnancy or severe liver or kidney dysfunction. Clinicians determined the choice of oral anticoagulant based on routine practice.
The authors gathered clinical and imaging data at baseline and at 3, 6, and 12 months. The primary outcome was a composite of symptomatic venous thromboembolism (VTE) and major bleeding within 6 months. The researchers also examined secondary outcomes including mortality, disability using the Modified Rankin Scale, non-major bleeding, and venous recanalization on imaging.
Results
The researchers assigned 401 patients to receive DOACs and 218 to receive vitamin K antagonists. At 6 months, both groups showed a 3% rate of the primary outcome of VTE or major bleeding. The weighted odds ratio comparing DOACs to vitamin K antagonists was 0.99, indicating no meaningful difference. Additionally, the data revealed both groups had a non-significantly different 1% mortality rate.
Patients in the DOAC group and the vitamin K antagonist group also showed similar functional outcomes, with 5% and 7%, respectively, reaching Modified Rankin Scale scores of three to six at 6 months. Imaging follow up showed partial venous recanalization in over 80% of both groups, though full recanalization appeared more often in the vitamin K agonist group (58%) versus the DOAC group (38%).
The researchers did not observe clear clinical consequences tied to that difference. They also found no evidence of harm from DOACs in patients with antiphospholipid antibodies, although that subgroup remained small.
Discussion
The authors concluded that DOACs provide a safe and effective alternative to vitamin K antagonists for patients with CVT. They emphasized the real-world relevance of their findings, noting that treatment decisions reflected typical clinical practice across diverse health care systems.
Although the study did not use randomization, the investigators applied rigorous statistical adjustment and blinded adjudication of outcomes, which strengthened the reliability of their conclusions.
A commentary published in The Lancet Neurology in March 2025 offered additional context to these findings. The commentary authors underscored that while the DOAC-CVT study represents the largest prospective investigation to date comparing DOACs and vitamin K antagonists in this population, the data also prompt important questions about treatment choice within the DOAC class.
Specifically, the authors highlighted that 11 of the 12 primary outcome events occurred in patients treated on dabigatran. Only one event occurred in a patient who received a factor Xa inhibitor.
In a post-hoc analysis, the study authors reported a weighted odds ratio of 1.54 for dabigatran versus vitamin K antagonists and 0.13 for factor Xa inhibitors versus vitamin K antagonists with respect to the composite primary outcome.
These findings suggest a possible safety advantage for factor Xa inhibitors over dabigatran, though the sample sizes remain too small to support definitive conclusions.
The commentary noted that this pattern mirrors trends seen in earlier studies such as CHOICE-CVT and RESPECT-CVT, which showed numerically higher event rates for dabigatran in some contexts, while factor Xa inhibitors appeared more favorable in observational data such as ACTION-CVT. ■