Direct oral anticoagulants for the treatment of venous thromboembolism in patients with active malignancy: a systematic review and meta-analysis

Low molecular weight heparins (LMWHs) are considered the standard of care for the treatment of venous thromboembolism (VTE) associated with cancer. We conducted a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) in patients with cancer. We systematically searched Medline for potential randomized-control clinical trials (RCTs) and post-hoc analyses. For each study, data on recurrent VTE, major or clinically relevant non-major bleeding (CRNMB), and major bleeding (MB) were extracted. Initially, a total of 1395 citations were identified. Eight studies met our eligibility criteria. The utilization of DOACs in patients with cancer showed a statistically significant reduction in the risk of VTE recurrence compared to LMWH or warfarin (RR = 0.64; 95% CI 0.46–0.88). Similar rates of major or CRNMB were observed between DOACs and LMWH or warfarin (RR = 1.00; 95% CI 0.75–1.33). There was no significant difference in the rate of MB between DOACs and LMWH or warfarin (RR = 1.31; 95% CI 0.71–2.44). Our results suggest that DOACs might reduce the incidence of VTE recurrence in patients with cancer without putting them at high risk for MB/CRNMB or MB. Our findings were mainly driven by the results of the Hokusai VTE Cancer trial. Given the level of investigated evidence, our findings should be interpreted with caution since the majority of the data were originated from sub-group analyses of large (RCTs). Future studies that are adequately powered are warranted to assess efficacy and safety data of DOACs for the treatment of VTE in patients with different types of cancer.