DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis

Low molecular weight heparins (LMWH) are the standard of care for the treatment of cancer-associated venous thromboembolism (CA-VTE). We performed a systematic review and meta-analysis to compare the effects of direct oral anticoagulants (DOAC) versus LMWH for the treatment of CA-VTE. The primary efficacy and safety outcomes were VTE recurrence and major bleeding (MB). The secondary outcomes were clinically relevant non-MB (CRNMB), all-cause mortality and the net clinical benefit. We searched MEDLINE, EMBASE, CENTRAL and Web of Science (inception-December 2019) and abstracts of relevant conferences (2000-2019) to identify randomized controlled trials comparing DOAC and LMWH for the treatment of CA-VTE. Relative risks (RR) and 95% confidence intervals were estimated (Mantel-Haenszel method, random-effects models). A non-inferiority analysis with a margin of 1.3 for the upper boundary of the RR was conducted for the primary outcomes. From 637 references, we included four publications which encompass three trials (1756 patients). Compared to LMWH, DOAC were associated with a trend for decreased VTE recurrence (RR 0.51; 95%CI 0.25-1.03; p = 0.06; I-2 = 51%), whereas MB (RR 1.64; 95%CI 1.00-2.69; p = 0.05; I-2 = 0%) and CRNMB (RR 1.83; 95%CI 1.04-3.20; p = 0.03; I-2 = 50%) were significantly more frequent with DOAC. Conversely, all-cause mortality (RR 1.06; 95%CI 0.83-1.35; p = 0.64; I-2 = 36%) and net clinical benefit (RR 0.74; 95%CI 0.38-1.42; p = 0.36; I-2 = 65%) were comparable. DOAC were non-inferior to LMWH in preventing CA-VTE recurrence, but were associated with an increased risk of MB and CRNMB. Further studies are required to confirm these results and inform on the risk/benefit ratio for specific populations.