In patients with cancer-associated thrombosis, direct oral anticoagulants significantly reduced the risk of recurrent venous thromboembolism compared to low-molecular-weight heparin (RR 0.66 in randomized controlled trials).
Meta-Analysis (n=49,824)
Do direct oral anticoagulants (DOACs) reduce recurrent venous thromboembolism and all-cause mortality without increasing major bleeding in patients with cancer-associated thrombosis compared to low-molecular-weight heparin?
In patients with cancer-associated thrombosis, DOACs significantly reduce recurrent VTE and all-cause mortality compared to LMWH at 6 months, with comparable overall major bleeding risk.
Relative Risk: 0.66 (95% CI 0.49–0.87)
Absolute Event Rate: 5.2% vs 8.2%
BACKGROUND: Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations. OBJECTIVE: This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis. RESULTS: Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk RR 0.66, 95% confidence interval CI 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72). CONCLUSIONS: In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.
Kang et al. (2026) conducted a meta-analysis in Cancer-associated thrombosis (n=49,824). Direct oral anticoagulants vs. Low-molecular-weight heparin was evaluated on Recurrent venous thromboembolism (RCTs) (RR 0.66, 95% CI 0.49-0.87). In patients with cancer-associated thrombosis, direct oral anticoagulants significantly reduced the risk of recurrent venous thromboembolism compared to low-molecular-weight heparin (RR 0.66 in randomized controlled trials).