Clinical and Safety Outcomes Associated with Extended Treatment of Venous Thromboembolism: A Network Meta-Analysis

Background: Many anticoagulant strategies are available for the extended treatment of venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe. Aim: A network meta-analysis was performed to resolve this uncertainty. Methods: We searched the medical literature through June 2022 for randomized controlled trials (RCTs) evaluating the efficacy and safety of anticoagulants for adults with VTE compared with other anticoagulants or a placebo. Results: We identified 13 eligible RCTs in 12 articles. All pooled hazard ratios (HR) and 95% credible intervals (CrI) mentioned below, except that for aspirin, were calculated by comparison with standard-intensity warfarin. Novel oral anticoagulants (NOACs) were not inferior to standard-intensity warfarin in preventing recurrence, and edoxaban was ranked first among the NOACs (HR, 0.99; 95% CrI, 0.70-1.39). All the NOACs, except rivaroxaban, were superior to standard-intensity warfarin in preventing bleeding events. Apixaban was ranked first and was considered to be safer than other NOACs for control of both major bleeding (HR = 0.07, 95% CrI: 0.01-0.37) and clinically relevant non-major bleeding (CRNMB, HR = 0.30, 95% CrI: 0.13-0.67). Edoxaban was ranked second among the NOACs for control of major bleeding (HR = 0.44, 95% CI: 0.21-0.88), and dabigatran was ranked second among the NOACs for control of CRNMB (HR = 0.54, 95% CrI: 0.4-0.73). Conclusions: There existed no statistically significant differences in recurrence between NOACs and standard-intensity warfarin, and NOACs were associated with a lower risk of bleeding events. Edoxaban effectively prevented VTE recurrence and major bleeding, and apixaban was the best anticoagulant for controlling bleeding events.