Efficacy and safety of anticoagulant agents in patients with venous thromboembolism and cancer: A network meta-analysis

Background: Low-molecular-weight heparins (LMWHs) are the recommended treatment for cancer-associated venous thrombosis (CAT). Recent evidences suggest a role for direct-acting oral anticoagulants (DOACs) in this clinical setting. Methods: To evaluate the efficacy and safety of different anticoagulants we performed a network meta-analysis of RCTs including patients with CAT treated with LMWHs, vitamin K antagonists (VKAs) or DOACs. MEDLINE and EMBASE were searched up to February 2018. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Results: Overall, 4720 CAT patients from 12 studies were included: 1430 from 2 studies comparing DOACs with LMWHs, 1212 from 4 studies comparing DOACs with VKAs and 2078 from 6 studies comparing VKAs to LMWHs. Recurrent VTE occurred in 4.9% of patients receiving DOACs, 9.6% receiving VKAs and 8.4% receiving LMWHs. The network meta-analysis showed a not significant increase of recurrent VTE in patients receiving LMWHs compared to those receiving DOACs (RR 1.3, 95% CI 0.9 to 2.0). The risk of recurrent VTE was higher in patients receiving VKAs compared to LMWHs (RR 1.5, 95% CI 1.0 to 2.0) or DOACs (RR 2.0, 95% CI 1.3 to 3.0) with no heterogeneity. Major bleeding occurred in 4.9, 4.1 and 4.3% of patients with CAT treated with DOAC, VKA or LMWH, respectively. No significant differences were observed from the direct, indirect and network meta-analyses. Conclusion: In patients with CAT, DOACs showed a good efficacy and safety profile compared to other anticoagulants and is candidates to be an alternative to LMWHs.