Direct oral anticoagulants for venous thromboembolism in cancer patients: a systematic review and network meta-analysis

Background The efficacy and safety of direct oral anticoagulants (DOACs), including dabigatran, apixaban, rivaroxaban, and edoxaban, for preventing and treating venous thromboembolism (VTE) in patients with cancer is unclear. Methods We searched the PubMed, Embase, Web of Science, and Cochrane Library databases from the establishment to November 30, 2021. In the frequency-based network meta-analysis, the odds ratio with a 95% confidence interval was reported. The relative ranking probability of each group was generated based on the surface under the cumulative ranking curve (SUCRA). Results We included 15 randomized controlled trials involving a total of 6162 patients. Apixaban reduced the risk of VTE compared with low-molecular heparin [OR = 0.53, 95% CI (0.32, 0.89)]. The efficacy of drugs was ranked from highest to lowest as follows: apixaban (SUCRA, 81.0), rivaroxaban (73.0), edoxaban (65.9), dabigatran (51.4), warfarin (30.8), and low-molecular-weight heparin (LMWH) (27.4). Edoxaban increased the risk of major bleeding compared with LMWH [OR = 1.83, 95% CI (1.04, 3.22)]. The safety of drugs was ranked from highest to lowest as follows: major bleeding-apixaban (SUCRA, 68.5), LMWH (55.1), rivaroxaban (53.0), warfarin (35.9), dabigatran (29.2), edoxaban (16.5) and clinically relevant non-major bleeding-LMWH (73.0), apixaban (57.8), edoxaban (45.8), rivaroxaban (35.3), and warfarin (10.8). Conclusions For preventing and treating VTE, in terms of VTE occurrence and major bleeding, apixaban had the lowest risk; in terms of clinically relevant non-major bleeding, LMWH had the lowest risk, followed by apixaban. Generally, apixaban is the most efficient and safest DOAC and presents better efficacy and relatively low bleeding risk among the VTE prevention and treatment drugs for patients with cancer.