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Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis

Li, A. and Garcia, D. A. and Lyman, G. H. and Carrier, M.

Thromb Res (2019) 173: 158–163

DOI: 10.1016/j.thromres.2018.02.144

Abstract

INTRODUCTION: It is unclear if direct oral anticoagulants (DOACs) are effective and safe alternatives to low-molecular-weight heparin (LMWHs) for the treatment of cancer-associated venous thromboembolism (VTE). We aim to synthesize existing literature that compared DOACs versus LMWHs in this high-risk population. MATERIALS AND METHODS: We conducted a systematic review using EMBASE, MEDLINE and CENTRAL for all observational studies and randomized controlled trials (RCTs) (PROSPERO: CRD42017080898). Two authors independently reviewed study eligibility, extracted data, and assessed bias. Primary outcomes included 6-month recurrent VTE and major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB) and mortality. RESULTS: We screened 426 articles, reviewed 25 in full-text, and selected 13 and 2 for qualitative and quantitative synthesis, respectively. Based on a meta-analysis of the 2 RCTs, DOACs had lower 6-month recurrent VTE (42/725) when compared to LMWH (64/727) (RR: 0.65 (0.42-1.01)). However, DOACs had higher major bleeding (40/725) when compared to LMWH (23/727) (RR 1.74 (1.05-2.88)). Similarly, CRNMB was higher (RR 2.31 (0.85-6.28)) for patients receiving DOACs. There was no difference in mortality (RR 1.03 (0.85-1.26)). Observational studies were heterogeneous with high risks of bias but showed recurrent VTE rates consistent with the meta-analysis. CONCLUSIONS: DOACs were more effective than LMWHs to prevent recurrent VTE but were associated with a significantly increased risk of major bleeding as well as a trend toward more CRNMB. The absolute risk differences were small (2-3%) for both primary outcomes and may reflect better compliance with DOACs than LMWHs.

Citation

Li, A., Garcia, D. A., Lyman, G. H., & Carrier, M. (2019). Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis. Thromb Res, 173, 158–163. https://doi.org/10.1016/j.thromres.2018.02.144 Humans, Administration, Oral, *Heparin, use, *Factor Xa inhibitors, *Low-molecular-weight, *Neoplasms, *Venous thrombosis, Anticoagulants/administration & dosage/adverse effects/*therapeutic use, Hemorrhage/chemically induced, Heparin, Low-Molecular-Weight/administration & dosage/adverse effects/*therapeutic, Neoplasms/*complications, Secondary Prevention, Thrombosis/*drug therapy/*etiology, Venous Thromboembolism/*drug therapy/*etiology

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