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DOI: 10.1055/a-2798-0066
Original Article

Reduced compared with standard dose direct oral anticoagulant for extended treatment of venous thromboembolism: A systematic review and meta-analysis

Authors

  • Carmen Ka Man Cheung 

    1   Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, Hong Kong (Ringgold ID: RIN13621)
    2   Department of Medicine, McMaster University, Hamilton, Canada (Ringgold ID: RIN3710)
    3   Population Health Research Institute, Hamilton, Canada (Ringgold ID: RIN33493)

  • Stephanie Carlin

    4   McMaster University Department of Medicine, Hamilton, Canada (Ringgold ID: RIN152997)
    3   Population Health Research Institute, Hamilton, Canada (Ringgold ID: RIN33493)
    5   Department of Medicine, Hamilton Health Sciences, Hamilton, Canada (Ringgold ID: RIN3708)

  • Thomas C. Scheier

    4   McMaster University Department of Medicine, Hamilton, Canada (Ringgold ID: RIN152997)
    3   Population Health Research Institute, Hamilton, Canada (Ringgold ID: RIN33493)

  • Qilong Yi

    6   Department of Epidemiology and Community Medicine, University of Ottawa School of Epidemiology and Public Health, Ottawa, Canada (Ringgold ID: RIN177403)

  • Noel C. C. Chan

    4   McMaster University Department of Medicine, Hamilton, Canada (Ringgold ID: RIN152997)
    3   Population Health Research Institute, Hamilton, Canada (Ringgold ID: RIN33493)
    7   The Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada (Ringgold ID: RIN139264)

  • Vinai Bhagirath

    2   Department of Medicine, McMaster University, Hamilton, Canada (Ringgold ID: RIN3710)
    3   Population Health Research Institute, Hamilton, Canada (Ringgold ID: RIN33493)
    7   The Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada (Ringgold ID: RIN139264)

  • Jo-Anne Petropoulos

    8   McMaster University Libraries, Hamilton, Canada

  • Raymond Wong

    1   Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, Hong Kong (Ringgold ID: RIN13621)

  • Jeffrey I Weitz

    7   The Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada (Ringgold ID: RIN139264)
    9   Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada (Ringgold ID: RIN3710)
    10   Department of Medical Sciences, McMaster University, Hamilton, Canada (Ringgold ID: RIN3710)

  • John W Eikelboom

    2   Department of Medicine, McMaster University, Hamilton, Canada (Ringgold ID: RIN3710)
    3   Population Health Research Institute, Hamilton, Canada (Ringgold ID: RIN33493)
    5   Department of Medicine, Hamilton Health Sciences, Hamilton, Canada (Ringgold ID: RIN3708)
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Introduction:Reduced-dose direct oral anticoagulants (DOACs) may provide similar efficacy with less bleeding than standard-dose for extended venous thromboembolism (VTE) treatment. It is unclear whether standard-dose are preferable in certain subgroups. Methods:We systematically searched MEDLINE, EMBASE, EMCARE, and CENTRAL for randomized trials comparing reduced- with standard-dose DOACs for extended VTE treatment.(INPLASY202550061) Outcomes included recurrent VTE, major bleeding, clinically relevant non-major bleeding (CRNMB), and mortality. Results: Five trials (8,781 patients) were included. Reduced-dose DOACs (apixaban 2.5mg twice daily or rivaroxaban 10mg once daily, n=4,395), compared to standard-dose (apixaban 5mg twice daily or rivaroxaban 20mg once daily, n=4,386), resulted in similar rates of recurrent VTE (1.66% vs 1.78%; risk ratio [RR] 0.94, 95% confidence interval [CI] 0.68–1.29). Major bleeding was less frequent with reduced-dose (1.16% vs 1.96%; RR 0.62, 95% CI 0.42–0.92), as was CRNMB (5.16% vs 7.00%; RR 0.75, 95% CI 0.63–0.88). Mortality rates were comparable (4.91% vs 5.81%; RR 0.86, 95% CI 0.63–1.17). These results held for high-risk subgroups, including patients with recurrent VTE or active cancer, except that reduced-dose DOACs appeared to lower recurrent VTE risk in males but increase risk in females (p=0.04). Risk of bias was rated “low” in four studies and “some concerns” in one study. Certainty of evidence was moderate for three outcomes and low for one outcome. Conclusion:For extended VTE treatment, reduced-dose DOACs have a similar risk of recurrent VTE and a lower risk of major and CRNMB compared to standard-dose, including in high-risk patients. A potential interaction with sex warrants further investigation



Publication History

Received: 16 December 2025

Accepted: 26 January 2026

Accepted Manuscript online:
30 January 2026

© . The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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Bibliographical Record
Carmen Ka Man Cheung, Stephanie Carlin, Thomas C. Scheier, Qilong Yi, Noel C. C. Chan, Vinai Bhagirath, Jo-Anne Petropoulos, Raymond Wong, Jeffrey I Weitz, John W Eikelboom. Reduced compared with standard dose direct oral anticoagulant for extended treatment of venous thromboembolism: A systematic review and meta-analysis. TH Open ; 0: a27980066.
DOI: 10.1055/a-2798-0066