Treatment of venous thromboembolism in cancer patients: a systematic review and meta-analysis on the efficacy and safety of different direct oral anticoagulants (DOACs)

BACKGROUND: To evaluate the efficacy and safety of different direct oral anticoagulants (DOACs) compared with low molecular weight heparins (LMWHs) in the treatment of venous thromboembolism (VTE) in cancer patients. METHODS: Literature was searched in databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (PubMed). Eligible studies were included, and data were collected independently by 2 reviewers. We conducted a systematic review of the efficacy and safety of DOACs in the treatment of VTE in cancer patients. The odds ratios (ORs) of different DOACs compared with LMWHs for VTE, deep vein thrombosis (DVT), pulmonary embolism (PE) recurrence, major bleeding, and clinically relevant non-major bleeding (CRNMB), were calculated in meta-analyses and subgroup analyses. RESULTS: A total of 18 articles were eligible for analyses, including 4 randomized controlled trials (RCTs) and 14 retrospective studies. Both RCTs and retrospective studies confirmed that DOACs decreased the risk of VTE recurrence [RCTs: OR, 0.60; 95% confidence interval (CI), 0.45–0.80; retrospective studies: OR, 0.73; 95% CI, 0.59–0.90] and DVT recurrence (RCTs: OR, 0.54; 95% CI, 0.36–0.80; retrospective studies: OR, 0.20; 95% CI, 0.06–0.63), but not PE recurrence or fatal PE in cancer patients. Subgroup analyses revealed an important role of rivaroxaban in decreasing recurrent VTE. Meanwhile, major bleeding events were not increased in the DOAC group, but the risks of CRNMBs were significantly elevated. Subgroup analyses confirmed the role of rivaroxaban in increasing the risk of major bleeding events and CRNMBs. CONCLUSIONS: Compared with LMWHs, DOACs (especially rivaroxaban) significantly reduce the risk of VTE and DVT, but not PE recurrence, in patients with cancer. Although DOACs did not increase the major bleeding events in pooled analysis, rivaroxaban showed an elevated risk of this adverse effect in subgroup analysis. In addition, the risk of CRNMB events was increased after the application of DOACs including rivaroxaban.