Direct oral anticoagulants for cancer-associated venous thromboembolisms: a systematic review and network meta-analysis

Background Several recent randomised controlled trials (RCT) have investigated the use of direct oral anticoagulants (DOAC) in the treatment of malignancy-associated venous thromboembolism (VTE). Aims This meta-analysis combines all RCT data to determine the risks of recurrent VTE and bleeding with DOAC in patients with malignancy-associated VTE compared with low-molecular-weight heparin (LMWH). Methods The study followed PRISMA guidelines. MEDLINE, EMBASE and CENTRAL were systematically searched from inception to 1 April 2020. References of reviews and relevant conference proceedings were searched by hand. Two authors independently evaluated study eligibility, extracted data and assessed risk of bias. Direct and indirect meta-analyses were performed. Results In four RCT with low risk of bias (2907 patients), high certainty evidence suggested that DOAC had a 37% reduction in risk of recurrent VTE compared with LMWH (direct pooled risk ratio (RR) 0.63; 95% confidence interval (CI) 0.44-0.91; I-2 = 28%). No significant difference was observed in the risk of major bleeding with DOAC compared with LMWH (RR 1.31; 95% CI 0.83-2.07; I-2 = 22%; moderate certainty evidence), including in patients in gastrointestinal and genitourinary malignancy. An increased risk of combined major or clinically relevant non-major bleeding was seen with DOAC (RR 1.52; 95% CI 1.09-2.12; I-2 = 51%; low certainty evidence). Apixaban had the highest probability of being ranked the most effective and least bleeding risk among the DOAC. Conclusion DOAC are effective in treating malignancy associated VTE; however, caution is required in patients with high risk of bleeding. Apixaban had lower risk of bleeding compared to other DOAC in this population.