Reduced Versus Full-Dose Direct Oral Anticoagulants for Long-Term Management of Venous Thromboembolism: A Systematic Review

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Background: Venous thromboembolism (VTE) is still a serious clinical problem because many patients still have a significant chance of having it happen again after their first course of anticoagulation is over. In recent years, reduced-dose direct oral anticoagulants (DOACs) have been investigated as a means to ensure prolonged protection while diminishing the risk of bleeding complications. This systematic review aims to summarize the available evidence comparing reduced-dose and full-dose DOAC regimens during the extended phase of VTE treatment. Methods: A systematic search of PubMed and the Cochrane Library (January 2010–November 2025) identified randomized trials and one ambispective cohort study evaluating reduced-dose apixaban (2.5 mg BID), rivaroxaban (10 mg OD), dabigatran (110 mg BID), or edoxaban (30 mg OD). Methodological quality was assessed using RoB-2 for trials and the Newcastle–Ottawa Scale for observational data. Because of differences in study designs and outcome definitions, a narrative synthesis was applied. Results: Five studies met the inclusion criteria. Across trials, reduced-dose DOACs maintained consistently low rates of recurrent VTE: 1.7% in AMPLIFY-EXT versus 8.8% with placebo; 1.2–1.5% in EINSTEIN CHOICE versus 4.4% with aspirin; 2.2% in RENOVE versus 1.8% with full-dose therapy; and 1.3% in HI-PRO versus 10% with placebo. Real-world data from Valeriani et al. showed only a single recurrence (0.7%) over nearly three years. Major bleeding remained uncommon, ranging from 0.1 to 0.5% in randomized trials and 2.1–2.9% in longer-term observational cohorts. Conclusions: In summary, reduced-dose DOACs appear to offer a favorable balance of safety and efficacy, providing durable protection against recurrence with a lower bleeding burden. These findings support their role as a practical extended-treatment strategy in clinical practice.

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