Direct oral anticoagulants compared to low molecular weight heparin for the treatment of venous thromboembolism among individuals with gastrointestinal cancer: an updated meta-analysis

Cancer, particularly gastrointestinal cancer, is associated with a higher risk of venous thromboembolism. Recent studies have increasingly compared direct oral anticoagulants (DOACs) with low molecular weight heparin (LMWH) for treating venous thromboembolism (VTE) in patients with gastrointestinal cancer. This meta-analysis aimed to investigate the efficacy of DOACs compared to LMWH for VTE in patients with gastrointestinal cancer. PubMed, the Cochrane Library, Scopus, and Web of Science were systematically searched from the inception to February 20, 2025, to identify randomized controlled trials (RCTs) or cohort studies comparing the effect of DOACs with LMWH on VTE recurrence, clinically relevant non-major bleeding, and major bleeding among patients with active gastrointestinal cancer suffering from VTE. Finally, 13 studies, including 8 cohort studies and 5 RCTs, were included. The random-effects model revealed that compared to using LMWH, the risk of VTE recurrence (risk ratio (RR) 0.75, 95% confidence interval (CI) (0.59, 0.97), I2 = 0.00%) was significantly decreased and the risk of clinically relevant non-major bleeding (RR 1.64, 95% CI (1.10, 2.45), I2 = 59.79%) was significantly increased when using DOACs; however, the risk of major bleeding (RR 1.16, 95% CI (0.86, 1.56), I2 = 28.51%) did not significantly change. RCTs suggested no significant change (RR 0.80, 95% CI (0.50, 1.27), I2 = 0.00%) in the risk of VTE recurrence, but cohort studies indicated a decreased risk (RR 0.73, 95% CI (0.54, 0.99), I2 = 0.00%) of VTE recurrence when using DOACs instead of LMWH. Both cohort studies (RR 1.02, 95% CI (0.75, 1.39), I2 = 20.43%) and RCTs (RR 1.65, 95% CI (0.89, 3.07), I2 = 26.59%) showed no significant difference in the risk of major bleeding when using DOACs instead of LMWH. RCTs showed an elevated risk (RR 2.32, 95% CI (1.48, 3.64), I2 = 0.00%) of clinically relevant non-major bleeding when using DOACs, but cohort studies reported no significant change (RR 1.40, 95% CI (0.86, 2.29), I2 = 60.84%) in the risk of clinically relevant non-major bleeding. Among patients with gastrointestinal cancer, compared to LMWH, DOACs may not increase the risk of VTE recurrence and major bleeding, but may increase the risk of clinically relevant non-major bleeding.