“efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin for recurrent VTE in cancer patients: A grade-assessed comprehensive meta-analysis of expanded outcomes from randomized controlled trials.”

Abstract Background: Venous thromboembolism (VTE) is a significant clinical complication in oncology, with a high prevalence among cancer patients. Conventional therapy, such as low-molecular-weight heparin (LMWH), has long-term compliance issues, especially in advanced cancer patients. Direct oral anticoagulants (DOACs) have emerged as a potential alternative, offering benefits like oral administration and predictable pharmacokinetics. However, concerns about their safety profile, particularly the risk of bleeding, remain, especially in high-risk cancer populations. Objective: This study aims to perform a meta-analysis comparing the efficacy and safety of DOACs versus LMWH for the management of cancer-associated VTE, with a focus on recurrent VTE, major bleeding, clinically relevant non-major bleeding (CRNMB), and other key outcomes such as all-cause mortality, deep vein thrombosis (DVT), and pulmonary embolism (PE). Methods: We have carried out a systematic review and meta-analysis in accordance with the PRISMA statements. Searches of various databases, such as PubMed, Scopus, and Cochrane, were conducted, with a total of 12 randomized controlled trials (RCTs) identified. The Cochrane RoB 2.0 tool was used to measure the risk of bias, and the GRADE system was used to judge the quality of evidence. A random-effects model was used to synthesize the outcomes, and the I 2 statistic was used to evaluate statistical heterogeneity. Results: Twelve studies involving a total of 8,925 patients were analyzed. The use of DOACs was associated with a significant reduction in the risk of VTE recurrence (RR: 0.70, 95% CI: 0.58-0.83), with no notable increase in major bleeding risk (RR: 1.08, 95% CI: 0.79-1.48). No significant differences were observed in CRNMB incidences, all-cause mortality, or PE. The occurrence of DVT also decreased notably with DOACs (RR: 0.55, 95% CI: 0.32-0.94). Subgroup analyses showed varying effects among different DOAC agents, with the greatest benefit in preventing recurrent VTE seen in the rivaroxaban subgroup. Conclusion Our findings suggest that DOACs are an effective alternative to LMWH in the management of cancer-associated VTE, with comparable safety profiles. Although they significantly reduce the risk of recurrent VTE and DVT, concerns regarding bleeding risk, particularly in specific cancer subtypes, require careful consideration. Further studies are needed to refine the clinical application of DOACs in high-risk cancer patients. Keywords: Venous thromboembolism, direct oral anticoagulants, low-molecular-weight heparin, cancer, recurrence, bleeding, meta-analysis, randomized controlled trials.