A network meta-analysis of direct factor Xa inhibitors for the treatment of cancer-associated venous thromboembolism

Abstract

Introduction Treatment of cancer-associated venous thromboembolism (CAVTE) remains challenging. The aim of this study was to assess the outcomes of direct acting oral anticoagulants (DOAs) for the treatment of CAVTE. Materials and methods A network meta-analysis of randomized clinical trials comparing DOAs (Apixaban, Rivaroxaban, and Edoxaban) versus Dalteparin for the treatment of CAVTE was performed. Outcomes of interest included, VTE recurrence, all-cause mortality, event-free survival, major bleeding, and clinically relevant non-major bleeding (CRNMB). Analysis was based on a random effects model and Bayesian Markov-chain Monte Carlo method was used for indirect comparisons. Results Four RCTs involving 2894 patients were included. Overall certainty of evidence was moderate regarding all outcomes. DOAs exhibited lower risk of VTE (RR 0.62; 95% CI 0.44, 0.87; P = 0.007), similar risk of major bleeding (RR 1.33; 95% CI 0.84, 2.11; P = 0.23), and higher risk of CRNMB (RR 1.66, 95% CI 1.08, 2.56; P = 0.02), compared with Dalteparin. Risk of all-cause mortality and event-free survival were similar between groups with RR 0.99 (95% CI 0.84, 1.16) and RR 1.03 (95% CI 0.94, 1.13), respectively. Apixaban ranked first for recurrent VTE (42.4%) and major bleeding (62.3%) and Dalteparin ranked first for CRNMB (54.7%). Rivaroxaban ranked best considering all-cause mortality (58.7%); Apixaban ranked best for event-free survival (83.6%). Conclusions DOAs presented a reduced risk of recurrent VTE with similar risk of major bleeding compared to Dalteparin. However, a higher risk of CRNMB is expected when this cohort of patients are treated with DOAs instead of Dalteparin.