The Role of Anticoagulation on Venous Thromboembolism Primary Prophylaxis in Low- to Intermediate-Risk Ambulatory Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The role of anticoagulants in the primary prevention of venous Thromboembolism(VTE) in high-risk cancer patients has been proven in previous studies; however, the routine use of thromboprophylaxis in cancer patients with Khorana score≤ 2 is still debated. This systematic review and meta-analysis aimed to investigate the role of prophylaxis with anticoagulants in cancer patients with low to moderate risk for first time.

Methods: PubMed, Scopus, Google Scholar, and Web of Science databases were searched with Mesh terms to find Randomized controlled trial studies (RCTs) that evaluated the effect of thromboprophylaxis against placebo on VTE up to January 2024 in low-risk cancer patients. This systematic review was conducted based on the PRISMA guidelines. Heterogeneity between studies was evaluated using the I2 test. Egger's test was used to check publication bias. In general, 21 studies with 9985 participants were included.

Results: The majority of studies had high quality and low risk of bias. The pooled estimate showed that using anticoagulants compared to placebo significantly reduces the risk of VTE (HR: 0.53, 95% CI: 0.43, 0.60, I2: 8.1%). Analysis of subgroups based on the class of anticoagulants showed that both direct oral anticoagulants (DOACs) (HR: 0.46, 95% CI: 0.36, 0.56, I2:8.5%) and Low molecular weight heparin (LMWH) (HR: 0.60, 95% CI: 0.51, 70, I2:0%) were significantly related to VTE risk compared to placebo. A pooled estimate of 18 studies did not show a significant association between increased major bleeding and anticoagulant prophylaxis. (HR: 1.25, 95% CI: 0.96, 1.54, I2: 4%).

Conclusion: Anticoagulant prophylaxis with both classes of LMWHs and DOACs compared to placebo can be associated with a reduction in VTE risk in low-to-intermediate risk cancer patients. DOACs were associated with a greater reduction in VTE risk. Anticoagulant prophylaxis had no significant relationship with increased major bleeding.