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Thromb Haemost
DOI: 10.1055/a-2788-3034
Original Article: Stroke, Systemic or Venous Thromboembolism

Efficacy and Safety of DOACs for the Treatment of Superficial Vein Thrombosis: A Systematic Review and Meta-Analysis

Authors

  • Andrea Boccatonda

    1   Diagnostic and Therapeutic Interventional Ultrasound Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy

  • Alice Brighenti

    1   Diagnostic and Therapeutic Interventional Ultrasound Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi, Bologna, Italy

  • Chiara Simion

    2   Department of Medicine, General Medicine and Thrombotic and Hemorrhagic Diseases Unit, University Hospital of Padova, Padova, Italy

  • Paolo Simioni

    2   Department of Medicine, General Medicine and Thrombotic and Hemorrhagic Diseases Unit, University Hospital of Padova, Padova, Italy

  • Elena Campello

    2   Department of Medicine, General Medicine and Thrombotic and Hemorrhagic Diseases Unit, University Hospital of Padova, Padova, Italy
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Graphical Abstract

Abstract

Background

Direct oral anticoagulants (DOACs) are increasingly used for superficial vein thrombosis (SVT), yet evidence remains limited. This systematic review and meta-analysis synthesizes all available data on the efficacy and safety of DOACs in SVT.

Methods

A systematic search identified randomized and observational studies enrolling adults with acute SVT treated with DOACs. Primary efficacy outcomes were venous thromboembolism (VTE: deep vein thrombosis or pulmonary embolism) and SVT recurrence/extension. Safety outcomes included major and clinically relevant non-major bleeding (CRNMB).

Results

Six studies (n = 2,040; 602 DOAC-treated patients) met the inclusion criteria. Compared with fondaparinux, DOACs showed comparable short-term efficacy for VTE prevention (pooled risk ratio [RR] 0.93, 95% CI 0.44–1.99) and similar rates of SVT recurrence (RR 1.30, 95% CI 0.65–2.62). Versus placebo, rivaroxaban reduced recurrence by approximately 80% (RR 0.20, 95% CI 0.03–1.35). In the pooled safety analysis including four studies, DOACs were associated with a 65% relative risk reduction in major or CRNMB compared with fondaparinux or low-molecular-weight heparin (RR 0.35, 95% CI 0.15–0.83; I 2 = 0%). In the TROLL registry (n = 229; 74% DOAC), no major bleeding occurred among DOAC users, while 5-year cumulative VTE and SVT recurrence rates were each 15.9%. Certainty of evidence was moderate for efficacy and high for safety.

Conclusion

DOACs demonstrate efficacy comparable to fondaparinux and an excellent safety profile in SVT, supporting their use as a practical oral alternative. Long-term data indicate persistent thrombotic risk, suggesting potential benefit of extended low-dose prophylaxis in selected high-risk patients.

Keywords

superficial vein thrombosis - direct oral anticoagulants - rivaroxaban - fondaparinux - venous thromboembolism - anticoagulation

Data Availability Statement

All materials supporting the findings of this review are available upon reasonable request from the corresponding author. The data extraction forms, datasets generated or analyzed during the study, and analytic code used for quantitative synthesis are available in the Supplementary Materials (available in the online version only). All search strategies for each database are included as Supplementary Materials (available in the online version only).


Contributors' Statement

A.Boccatonda and A.Brighenti contributed equally to the conception, design, and drafting of the systematic review protocol and manuscript. C.S. and E.C. contributed to data extraction, risk of bias assessment, and critical revision of the manuscript for important intellectual content. P.S. provided overall supervision, methodological guidance, and final approval of the manuscript. All authors read and approved the final version of the manuscript and agree to be accountable for all aspects of the work.


Supplementary Material



Publication History

Received: 15 November 2025

Accepted after revision: 13 January 2026

Accepted Manuscript online:
15 January 2026

Article published online:
27 January 2026

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