SYSTEMATIC REVIEW article
Front. Cardiovasc. Med.
Sec. Thrombosis and Haemostasis
Full-dose versus reduced-dose comparison of direct oral anticoagulants for extended treatment of venous thromboembolism: a systematic review and meta-analysis of randomized controlled trials
Provisionally accepted
- 1Heze Municipal Hospital, Heze, China
- 2Binzhou People's Hospital, Binzhou, China
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Background: For patients requiring extended anticoagulation therapy, clinicians often prescribe reduced-dose direct oral anticoagulants(DOACs) rather than full-dose, which may be related to concerns about the higher bleeding risk associated with full-dose DOACs, despite potentially better efficacy in preventing VTE recurrence. This meta-analysis aims to evaluate the net clinical benefit of reduced-dose DOACs versus full-dose DOACs in extended anticoagulation therapy. Methods: This study has been registered in the International Prospective Register of Systematic Reviews(PROSPERO identifier: CRD420251089110). A systematic search was conducted in the PubMed, Embase, and Web of Science databases from their inception to June 30, 2025. Data extraction was done independently and in duplicate. A random-effects meta-analysis model was used to report the pooled treatment effects and 95% confidence intervals (CIs). Results: A total of 5 randomized clinical trials were included (8,781 cases) . Compared with full-dose DOAC, reduced-dose DOAC did not significantly increase the risk of recurrent VTE or death [(RR, 0.94 (95% CI, 0.68-1.29)), (RR, 0.84 (95% CI, 0.65-1.09))], but significantly reduced the risk of major bleeding/CRNMB (RR, 0.71 (95% CI, 0.61-0.82)). In the analysis of DOAC drugs, the prospective estimates for recurrent VTE were as follows: apixaban, RR, 0.93 (95% CI, 0.63-1.37); rivaroxaban, RR 0.96 (95% CI, 0.54-1.69). The prospective estimates for major bleeding/CRNMB were as follows: apixaban, RR, 0.74 (95% CI, 0.63-0.89); rivaroxaban, RR, 0.63 (95% CI, 0.48-0.84). Most findings were consistent within subgroups. Conclusion: Reduced-dose DOACs were associated with a significant decrease in the risk of major bleeding/CRNMB compared with full-dose DOACs, but were not associated with a significant increase in the risk of recurrent VTE. These findings support the net clinical benefit of reduced-dose DOACs compared with full-dose DOACs and reinforce adherence with current VTE guidelines.
Keywords: Dose, direct oral anticoagulants, Venous Thromboembolism, Extended treatment, randomized controlled trials
Received: 19 Sep 2025; Accepted: 14 Nov 2025.
Copyright: © 2025 Zhang, Wang, Li, Tian, Niu, Cheng and Niu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaofang Niu, nxf819@126.com
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