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DOAC-CVT

Direct oral anticoagulants versus vitamin K antagonists for cerebral venous thrombosis (DOAC-CVT): an international, prospective, observational cohort study

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Year of Publication: 2025

Authors: Anita van de Munckhof, Mayte Sánchez van Kammen, Turgut Tatlisumak, ..., Marialuisa Zedde

Journal: The Lancet Neurology

Citation: Lancet Neurol. 2025;24(3):199-207

Link: https://doi.org/10.1016/S1474-4422(24)00519-2

Clinical Question

Are direct oral anticoagulants (DOACs) as safe and effective as vitamin K antagonists (VKAs) for the treatment of cerebral venous thrombosis?

Bottom Line

The rate of recurrent venous thrombotic events and major bleeding did not differ between patients with CVT treated with DOACs versus VKAs. DOACs are a reasonable alternative treatment option to VKAs for CVT.

Major Points

  • Largest prospective cohort study comparing DOACs vs VKAs for CVT treatment (619 patients from 65 hospitals across 23 countries)
  • Primary composite endpoint (symptomatic VTE + major bleeding at 6 months) occurred in 3% of both groups (weighted OR 0.99)
  • No significant differences in mortality (1% vs 1%), functional independence, or individual endpoint components
  • Dabigatran was the most commonly used DOAC (67%), followed by apixaban (16%) and rivaroxaban (15%)
  • Most patients (90-97%) received lead-in heparin before starting oral anticoagulation
  • Complete recanalisation was less common in DOAC group (38%) vs VKA group (58%), though at least partial recanalisation was similar (82% vs 85%)
  • Results consistent with prior randomized trials (RESPECT-CVT, SECRET, CHOICE-CVT) and observational data (ACTION-CVT)

Design

Study Type: International prospective observational cohort study

Randomization:

Blinding: All VTEs, major bleeding events, clinically relevant non-major bleeding events, arterial thrombotic events, and deaths were assessed by an independent adjudication committee masked to the type of oral anticoagulant used

Enrollment Period: January 27, 2021 to January 15, 2024

Follow-up Duration: 6 months (with additional assessments at 3 and 12 months)

Centers: 65

Countries: Australia, Austria, Belgium, Brazil, Canada, Chile, China, Finland, Germany, India, Israel, Italy, Netherlands, Norway, Poland, Portugal, Romania, South Korea, Spain, Sweden, Switzerland, UK, USA

Sample Size: 619

Analysis: Intention-to-treat; inverse probability-of-treatment weighting to calculate weighted ORs for primary and secondary outcomes; propensity score model adjusted for age, eGFR, active cancer, CNS infections, antiplatelet use, country income status, GCS, ICH, antiphospholipid antibodies, previous bleeding, previous VTE; 1000 bootstrap resamples for 95% CIs

Inclusion Criteria

  • Adults aged ≥18 years at time of CVT diagnosis
  • Radiologically confirmed CVT
  • Starting oral anticoagulant treatment (DOAC or VKA) within 30 days after diagnosis
  • Included within 90 days of CVT diagnosis

Exclusion Criteria

  • Previous use of anticoagulants at time of CVT diagnosis
  • Absolute contraindication to DOACs (pregnancy, lactation, severe renal or liver disease)

Arms

FieldDOAC GroupControl
InterventionDirect oral anticoagulants: dabigatran etexilate (67%), apixaban (16%), rivaroxaban (15%), edoxaban (1%). Started within 30 days of CVT diagnosis, typically after lead-in heparin (median 6 days).Vitamin K antagonists (warfarin or equivalent). Started within 30 days of CVT diagnosis, typically after lead-in heparin (median 9 days).
DurationMedian 6 months; 23% stopped at 6 monthsMedian 6 months; 25% stopped at 6 months

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Composite of symptomatic recurrent VTE and major bleeding (ISTH criteria) at 6 monthsPrimary7/218 (3%)12/401 (3%)0.22%
All-cause mortality at 6 monthsSecondary3/218 (1%)3/401 (1%)0.55
Symptomatic recurrent VTE at 6 monthsSecondary3/218 (1%)6/401 (1%)1.45
Major bleeding at 6 monthsSecondary4/218 (2%)6/401 (1%)0.89
Clinically relevant non-major bleeding at 6 monthsSecondary3/218 (1%)9/401 (2%)1.77
Poor functional outcome (mRS 3-6) at 6 monthsSecondary16/215 (7%)20/390 (5%)0.71
Complete recanalisation at 6 monthsSecondary80/138 (58%)107/278 (38%)0.0002
Symptomatic Recurrent VTEAdverse3 (1%)6 (1%)1.45
Major BleedingAdverse4 (2%)6 (1%)0.89
Intracranial Haemorrhage (among major bleeds)Adverse2/5 (40%)2/7 (29%)

Subgroup Analysis

Exploratory analysis by DOAC type: dabigatran vs VKA weighted OR 1.54 (95% CI 0.46-4.37); factor Xa inhibitors vs VKA weighted OR 0.13 (95% CI <0.01-1.75). No events occurred in patients with antiphospholipid antibody syndrome in either group (n=13 total).

Criticisms

  • Observational study design with potential for residual confounding despite propensity score weighting
  • Underpowered to detect non-inferiority (would require ~2000 patients)
  • No central monitoring; local investigators responsible for data accuracy
  • INR values not collected for VKA group, so time in therapeutic range could not be assessed
  • Few patients with antiphospholipid antibody syndrome, limiting conclusions for this population
  • Follow-up imaging not available for all patients (69% DOAC, 63% VKA)
  • More patients in DOAC group from high-income countries (67% vs 42%)
  • Patients in DOAC group had less severe presentation (fewer focal deficits: 35% vs 50%)

Funding

Netherlands Thrombosis Foundation (project number 2020_02)

Based on: DOAC-CVT (The Lancet Neurology, 2025)

Authors: Anita van de Munckhof, Mayte Sánchez van Kammen, Turgut Tatlisumak, ..., Marialuisa Zedde

Citation: Lancet Neurol. 2025;24(3):199-207

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