Direct oral anticoagulant versus low-molecular-weight heparin for treatment of venous thromboembolism in cancer patients: An updated meta-analysis of randomized controlled trials

Background: Cancer associated venous thromboembolism (VTE) results in significant morbidity and mortality. Low molecular weight heparin (LMWH) has been standard of care for treatment of cancer-associated VTE, however direct oral anticoagulants (DOACs) are emerging as alternative treatment options.

Objective: To compare the benefits and harms of DOACs versus LMWH for treatment of VTE in cancer.

Data sources: MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception to April 2020.

Study selection: Randomized controlled trials (RCT) comparing DOACs with LMWH for treatment of VTE in cancer patients.

Data synthesis: Four good-quality RCTs, met inclusion criteria. Compared with LMWH, DOACs were associated with lower rates of VTE recurrence (RR 0.62; 95% CI: 0.44-0.87; P = 0.006), and DVT recurrence (RR 0.61; 95% CI: 0.4-0.94; P = 0.02) but not PE recurrence (RR 0.73; 95% CI: 0.51-1.04; P = 0.08), in cancer patients. However, the risk of clinically relevant non-major bleeding (CRNMB) (RR 1.58; 95% CI: 1.11-2.24; P = 0.01), and major bleeding in gastrointestinal cancer (RR 2.55; 95% CI 1.24-5.27, P = 0.01), were higher with DOACs. The risk of overall major bleeding (RR 1.33; 95% CI: 0.84-2.1; P = 0.22), all-cause mortality (RR 0.99; 95% CI: 0.84-1.17; P = 0.92), VTE-related mortality (RR: 1; 95% CI: 0.29-3.44; P = 1) and bleeding-related mortality (RR: 0.71; 95% CI: 0.17-2.91; P = 0.63), were similar in both treatment groups.

Conclusion: Among cancer patients with VTE, treatment with DOACs is associated with a significant reduction of VTE and DVT recurrence, compared to LMWH. These benefits were offset by an increased risk of CRNMB, and major bleeding in gastrointestinal cancer.