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

Background Several recent randomized controlled trials (RCTs) have investigated the use of direct oral anticoagulants (DOACs) in the treatment of malignancy associated venous thromboembolisms (VTE). Aims This meta-analysis combines all RCT data to determine the risks of recurrent VTE and bleeding with DOACs in patients with malignancy associated VTE compared to low molecular weight heparin (LMWH). Methods The study followed PRISMA guidelines. MEDLINE, EMBASE, CENTRAL were systematically searched from inception to 1st of April 2020. References of reviews and relevant conference proceedings were hand-searched. Two authors independently evaluated study eligibility, extracted data, and assessed risk-of-bias. Direct and indirect meta-analyses were performed. Results In four RCTs with low risk-of-bias (2907 patients), high certainty evidence suggested that DOACs had a 37% reduction in risk of recurrent VTE compared to LMWH (direct pooled risk ratio (RR) 0.63, 95%CI 0.44-0.91; I2 = 28%). No significant difference was observed in the risk of major bleeding with DOACs compared to LMWH (RR 1.31, 95%CI 0.83-2.07; I2 = 22%; moderate certainty evidence), including in patients in gastrointestinal and genitourinary malignancy. An increased risk of combined major or CRNMB was seen with DOACs (RR 1.52, 95%CI 1.09-2.12; I2 = 51%; low certainty evidence). Apixaban had the highest probability of being ranked most effective and least bleeding risk amongst the DOACs. Conclusion DOACs 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 DOACs in this population. This article is protected by copyright. All rights reserved.