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Observational Study
. 2025 Mar;24(3):199-207.
doi: 10.1016/S1474-4422(24)00519-2.

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

Anita van de Munckhof  1 , Mayte Sánchez van Kammen  1 , Turgut Tatlisumak  2 , Katarzyna Krzywicka  1 , Sanjith Aaron  3 , Florina Antochi  4 , Antonio Arauz  5 , Miguel A Barboza  6 , Adriana B Conforto  7 , Daniel Galdames Contreras  8 , Mirjam R Heldner  9 , Maria Hernández-Pérez  10 , Sini Hiltunen  11 , Xunming Ji  12 , Wayneho Kam  13 , Timothy J Kleinig  14 , Espen S Kristoffersen  15 , Ronen R Leker  16 , Robin Lemmens  17 , Sven Poli  18 , Mohammad Wasay  19 , Teddy Wu  20 , Nilüfer Yeşilot  21 , Jian Chen  22 , Maria Sofia Cotelli  23 , Jelle Demeestere  17 , Jiangang Duan  12 , Nesrin Ergin  24 , Tiago Esteves Freitas  25 , Ana Gomes  26 , Heleen M den Hertog  27 , Erik Lindgren  2 , Nicolas Martinez-Majander  11 , Issa Metanis  16 , Angel Miraclin  3 , Lucia Jansi Rani  3 , Y Muralidhar Reddy  28 , Shafaq Saleem  19 , Adrian Scutelnic  9 , Sathish Shanmugasundaram  3 , Ido R van den Wijngaard  29 , Işıl Yazıcı Gençdal  30 , Rik van Eekelen  31 , Jelle Vellema  1 , Marcel Arnold  9 , Lia Neto  32 , Saskia Middeldorp  33 , Diana Aguiar de Sousa  34 , Katarina Jood  2 , Jukka Putaala  11 , José M Ferro  35 , Jonathan M Coutinho  36 ; DOAC-CVT investigators
Collaborators, Affiliations
Observational Study

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

Anita van de Munckhof et al. Lancet Neurol. 2025 Mar.

Abstract

Background: There is an unmet need for high-quality data from prospective studies on the safety and effectiveness of direct oral anticoagulants (DOACs) for the treatment of cerebral venous thrombosis (CVT). We aimed to compare the safety and effectiveness of DOACs versus vitamin K antagonists (VKAs) for the treatment of CVT in a setting that reflects daily clinical practice.

Methods: DOAC-CVT was an international, prospective, observational cohort study done in 65 hospitals in 23 countries across five continents. Eligible patients were adults (aged ≥18 years) with radiologically confirmed CVT starting oral anticoagulant treatment with either DOACs or VKAs, as per local practice, within 30 days after diagnosis. Exclusion criteria were previous use of anticoagulants at the time of CVT diagnosis or an absolute contraindication to DOACs (eg, pregnancy and lactation, or severe renal or liver disease). Data were collected during routine clinical visits or telephone consultations at CVT diagnosis (baseline) and at 3 months, 6 months, and 12 months after CVT diagnosis. The primary endpoint was a composite of symptomatic venous thromboembolism and major bleeding events (International Society on Thrombosis and Haemostasis criteria) at 6 months. Main outcomes were adjusted for the confounders age, renal function, active cancer, CNS infections, concomitant antiplatelet use, country of inclusion's income status, Glasgow Coma Scale score, intracranial haemorrhage, antiphospholipid antibodies, previous major bleeding, and previous venous thromboembolism using inverse probability-of-treatment weighting. This study is registered at ClinicalTrials.gov (NCT04660747) and is ongoing.

Findings: Between Jan 27, 2021, and Jan 15, 2024, 619 patients were included; 401 (65%) patients started DOAC treatment, and 218 (35%) patients started VKA treatment. 390 (63%) of 619 patients were female and 229 (37%) of 619 patients were male. Patients' median age was 41 years (IQR 28-51). 6-month follow-up data were available for 617 (>99%) of 619 patients. 12 (3%) of 401 patients in the DOAC group and seven (3%) of 218 patients in the VKA group had a primary outcome event (weighted odds ratio [OR] 0·99 [95% CI 0·37-3·38]). Three (1%) of 401 patients in the DOAC group died versus three (1%) of 218 patients in the VKA group (weighted OR 0·55 [95% CI 0·11-2·80]).

Interpretation: The rate of recurrent thrombosis and major bleeding did not differ between patients with CVT treated with DOACs versus VKAs. This study adds to the increasing evidence that DOACs are a reasonable treatment option for CVT alongside VKAs.

Funding: Netherlands Thrombosis Foundation.

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Conflict of interest statement

Declaration of interests KK is treasurer of the Resident and Research Fellow Section of European Academy of Neurology. MAB received a grant from Boehringer Ingelheim, consulting fees from Roche Pharmaceuticals, honoraria from Roche Pharmaceuticals and Pfizer, and travel support from Boehringer Ingelheim. ABC reports grants from Sao Paulo Research Support Foundation and Brazilian Council of Scientific and Technological Development, consulting fees from Boehringer Ingelheim, honoraria from Brazilian Academy of Neurology and Eurofarma, advisory board participation for the OPTIMAL stroke trial, and is co-chair of the Research Committee for World Stroke Organization. MRH received grants from the Swiss National Science Foundation, SITEM Research Funds, and Swiss Heart Foundation and honoraria from MAS Stroke Medicine Bern. SH received lecture fees from Pfizer. ESK received research grants from Akershus University Hospital, University of Oslo, Foundation DAM, and Norwegian Epilepsy Association. RRL reports a research grant from the EU Horizon 2021, lecture fees from IscemaView and BI, is a national principal investigator for the OCEANIC STROKE study for Bayer, and is a national principal investigator for a phase 2 study of Shionogi. RL reports consulting fees from Boehringer Ingelheim and Pfizer. SP reports grants from BMS/Pfizer, Boehringer-Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, German Federal Ministry of Education and Research, Helena Laboratories, and Werfen, consulting fees from Alexion, AstraZeneca, Daiichi Sankyo, and Werfen, honoraria from Alexion, Bayer, Boehringer-Ingelheim, BMS/Pfizer, and Portola, and participation in an advisory board for the OPENS-2 trial. AG is a national RESQ coordinator. HMdH reports conducting lectures for U prevent. EL received grants from The Swedish Heart Lung Foundation, The Swedish Research Council, Swedish Neurological Society Elsa and Gustav Lindh's Foundation, Per Olof Ahl's Foundation, Ulla Amlöv Foundation, and Wennerström Foundation. AS received grants from the Swiss Heart Foundation and TEVA pharmaceuticals and support for attending meetings from AbbVie and TEVA pharmaceuticals. MA reports honoraria from AstraZeneca, Bayer, Sanofi, and Novartis and scientific advisory board participation for Amgen, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Novartis, and Novonordisk. SM received speaker fees from Sanofi and Viatris, and participated in steering committees for AstraZeneca, advisory boards for Alveron, Viatris, Norgine, and Hemab, and a data safety and monitoring board for Bayer. DAdS reports grants from MSD Clinical Research Grant 2023 and Portuguese Foundation for Science and Technology, speaker fees from Bial and AstraZeneca, advisory board participation for Johnson & Johnson, Daiichi Sankyo, and AstraZeneca, data safety monitoring board participation for University of British Columbia, and is a co-chair of Guideline Board European Stroke Organisation. KJ received funding from the Swedish state under the agreement between the Swedish government and the country councils, grants from the Swedish Stroke Association, and consulting fees from Janssen. JP reports honoraria from Bayer, Abbott, and BMS-Pfizer, advisory board participation for Novo Nordisk and Herantis Pharma, and stock options for Vital Signum. JMF received grants from Bayer and Daiichi Sankyo. JMC received funding from the Netherlands Thrombosis Foundation, grants from Bayer and AstraZeneca, and is cofounder and shareholder of TrianecT. All other authors declare no competing interests.

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