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

Abstract

IntroductionIt 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 methodsWe 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. ResultsWe 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. ConclusionsDOACs 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.