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de Lucena LA, Duarte AG, Hespanhol LC, et al. Reduced vs full-dose direct oral anticoagulants for extended treatment of cancer-associated venous thromboembolism: a systematic review and meta-analysis of randomized trials. J Thromb Haemost. 2025 Oct 16:S1538-7836(25)00645-2. doi: 10.1016/j.jtha.2025.09.026. (Systematic review)
Abstract

BACKGROUND: Patients with cancer-associated venous thromboembolism (VTE) are at high risk of recurrent thrombosis and bleeding during prolonged anticoagulation. While full-dose direct oral anticoagulants (DOACs) are widely used, the safety and efficacy of reduced-dose regimens for extended treatment remain uncertain.

OBJECTIVES: This study compared the safety and efficacy of reduced-dose vs full-dose DOACs in the extended treatment of cancer-associated VTE.

METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing reduced- and full-dose DOACs in adults with active cancer and VTE. Searches were performed in PubMed, Embase, and the Cochrane Library. The primary outcomes were a composite of VTE recurrence, major bleeding, or clinically relevant nonmajor bleeding, and the combined risk of major or clinically relevant nonmajor bleeding.

RESULTS: Three randomized controlled trials comprising 2361 patients were included. Two trials evaluated apixaban 2.5 mg vs 5 mg twice daily, and 1 evaluated rivaroxaban 10 mg vs 20 mg once daily. Reduced-dose DOACs were associated with a lower risk of the composite outcome (relative risk, 0.77; 95% CI, 0.64-0.93; P = .006) and reduced bleeding (relative risk, 0.76; 95% CI, 0.62-0.93; P = .008) than full-dose DOACs. No significant differences were observed in major bleeding, clinically relevant nonmajor bleeding, VTE recurrence, or all-cause mortality when analyzed individually.

CONCLUSIONS: Reduced-dose DOACs appear as effective as full-dose regimens for extended treatment of cancer-associated VTE, with a lower risk of bleeding. These findings support their use as a safer long-term anticoagulation strategy in selected patients.

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