Direct Oral Anticoagulant for the Treatment of VTE in Cancer Patients: A Systematic Review and Meta-analysis

Background: Recent clinical guidelines suggest direct oral anticoagulants (DOACs) as treatment for cancer-associated thrombosis (CAT), but the strength of such recommendations was not clear. Newly released trials add uncertainties to the benefit and risk assessment between DOACs and conventional therapy (low-molecular-weight heparin [LMWH] or vitamin K antagonists [VKAs]).

Objective: To evaluate the efficacy and safety of DOACs in patients with CAT, as compared with LMWH and VKAs.

Methods: PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) that reported outcomes of DOACs for treating CAT were included. Relative risk (RR), risk difference, and 95% CIs were pooled using the Mantel-Haenszel method.

Results: A total of 8 RCTs were included. DOACs significantly reduced VTE recurrence (RR = 0.59; 95% CI = 0.48-0.73) compared with conventional therapy. Results were similar in the LMWH and VKA subgroups. DOACs had a higher, though nonsignificant, risk of major bleeding compared with LMWH (RR = 1.33; 95% CI = 0.94-1.89) but lower risk of major bleeding compared with VKAs (RR = 0.60; 95% CI = 0.39-0.93). Findings were consistent across patients with active cancer and history of cancer.

Conclusion and relevance: DOACs have better efficacy to prevent recurrent VTE compared with conventional therapy. Regarding the safety profile, DOACs may carry higher risk of bleeding compared with LMWH but lower risk of bleeding compared with VKAs. Further studies are needed to inform the optimal anticoagulation approach for different types of cancers.

Keywords: anticoagulation; cancer; cancer-associated thrombosis; meta-analysis; systematic review; venous thromboembolism.