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

Many anticoagulant strategies are available for the extended treatment of venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe.

A network meta-analysis was performed to resolve this uncertainty.

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.

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).

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.