Efficacy and safety of direct oral anticoagulants vs. low molecular weight heparin for cancer-related venous thromboembolism: A meta-analysis of randomized trials

Aims: To examine the efficacy and safety of direct oral anticoagulants (DOACs) vs. low molecular weight heparin (LMWH) in patients with cancer-related venous thromboembolism (VTE). Methods and results: An electronic search of the MEDLINE, SCOPUS, and Cochrane databases without language restrictions was performed through April 2020 for randomized controlled trials that compared the outcomes with DOACs vs. LMWH among patients with cancer-related VTE. Summary estimates were reported using random effects model. The main efficacy outcome was VTE recurrence, while the main safety outcome was major bleeding. The final analysis included four randomized trials with a total of 2907 patients. The weighted mean follow-up was 6.1 months. Compared with LMWH, DOACs were associated with lower incidence of VTE recurrence [5.7% vs. 9.1%, risk ratio (RR) 0.62; 95% confidence interval (CI) 0.44-0.87; P = 0.01], driven by lower incidence of deep venous thrombosis (RR 0.60, 95% CI 0.39-0.93; P = 0.02). There was no difference in the incidence of major bleeding between DOACs and LMWH (4.8% vs. 3.6%, RR 1.33; 95% CI 0.84-2.11; P = 0.23). The incidence of all-cause mortality was similar (RR 0.99; 95% CI 0.84-1.16; P = 0.91). Subgroup analysis suggested no differences according to the type of DOAC regarding recurrent VTE or major bleeding (Pinteraction = 0.53 and Pinteraction = 0.11, respectively). Conclusion: Among patients with cancer-related VTE, DOACs were associated with lower incidence of VTE recurrence and no difference in the incidence of major bleeding compared with LMWH. Future studies examining the subset of cancer patients who drive the most benefit are encouraged.