Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin in patients with cancer: a systematic review and meta-analysis

The efficacy and safety of direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) are still debated in the treatment of patients with cancer, and the optimal duration of therapy remains uncertain. Electronic databases (PubMed, Embase, and Cochrane Library) were searched to retrieve studies on the efficacy and safety of DOACs versus LMWH in treating patients with cancer from January 1980 to October 2018. The primary efficacy and safety endpoints were recurrent venous thromboembolism (VTE) and major bleeding. Our study included two randomized controlled trials (RCTs) and nine observational studies, together comprising 4509 patients with cancer. The pooled estimates indicated that DOACs led to a modest reduction recurrent VTE in the RCTs [RR: 0.63, 95% confidence interval (CI), 0.42–0.96, P = 0.03] and in the observational studies (RR: 0.74, 95% CI, 0.58–0.93, P = 0.011), without increasing the risk of major bleeding for observational studies (P = 0.805), but increased for RCTs (P = 0.017). The same trends were observed in the rivaroxaban subgroup. Moreover, subgroup analyses according to the treatment duration indicated that DOACs significantly reduced the incidence of recurrent VTE (P = 0.006 at 6 months; P < 0.001 at 12 months) without significant differences in major bleeding compared with LMWH at 6 or 12 months. Patients with cancer who received DOACs exhibited a significant reduction in recurrent VTE with no increased risk of major bleeding compared with LMWH. DOACs may be an alternative choice for long-term anticoagulant therapy in patients with cancer.