Direct oral anticoagulants more effective than low-molecular-weight heparin for venous thrombo-embolism in cancer: an updated meta-analysis of randomized trials

In the recent past, low-molecular-weight heparin (LMWH) was the first choice in the treatment of cancer related venous thrombo-embolism (VTE). Evidence supporting the preferential use of direct anticoagulants (DOACs) in patients with cancer, instead, is less robust so far. We therefore aimed to assess in an updated meta-analysis of randomized controlled trials whether the use of DOACs may be associated with a more favorable profile when compared to LMWH. We performed a meta-analysis of RCTs enrolling patients with VTE and cancer. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for recurrence of VTE, major bleeding, and mortality comparing subjects treated with DOACs with those with LMWH. After study selection, three RCTs (HOKUSAI-Cancer, SELECT-D and ADAM-VTE) were included for the analysis with an overall population of 1739 patients. DOACs patients had a lower incidence of 6-month recurrent VTE when compared to LMWHs (RR 0.56, 95% CI 0.40-0.79; p < 0.001). Incidence of major bleeding was not significantly different between DOACs and LMWH treated patients (RR 1.56, 95% CI 0.95-2.47, p = n.s.), and mortality rates were comparable (RR 1.03, 95% CI 0.91-2.47, p = n.s.). In a meta-analysis of RCTs therapy with DOACs was superior to LMWH in terms of efficacy and lower recurrence of VTE with a comparable safety profile in terms of bleeding events and complications.