Achieving higher efficacy without compromising safety with factor XI inhibitors versus low molecular weight heparin for the prevention of venous thromboembolism in major orthopedic surgery—Systematic review and meta‐analysis

BACKGROUND: In recent years, many important advances have been seen in anticoagulation therapy. However, bleeding risk is still a major concern. Factor XI (FXI) inhibition has emerged as a potential advantageous target to minimize this risk. OBJECTIVES: We conducted a systematic review and meta‐analysis of current evidence on FXI inhibitors for thromboprophylaxis in major orthopedic surgery. METHODS: We performed a systematic search of electronic databases (PubMed, CENTRAL, and Scopus) until May of 2022. Studies were considered eligible if they were randomized controlled trials (RCTs) evaluating FXI inhibitors in thromboprophylaxis versus low molecular weight heparin (LMWH). For analysis purposes, we considered efficacy (venous thromboembolism [VTE], symptomatic VTE) and safety (major and clinically relevant non‐major [CRNM] bleeding events, major bleeding events, blood transfusion necessities, adverse events, major adverse events) outcomes. RESULTS: Overall, four RCTs were included, with a total of 2269 patients, 372 VTE events, and 50 major or CRNM bleeding events. Regarding efficacy outcomes, FXI inhibitors were associated with a significant reduction in the incidence of VTE events (odds ratio [OR] 0.50; 95% confidence interval [CI: 0.36, 0.69]). Concerning safety outcomes, FXI inhibitors significantly reduced major or CRNM bleeding events (OR 0.41; 95% CI [0.22, 0.75]). It was also associated with a lower percentage of patients needing a blood transfusion, despite not meeting statistical significance (OR 0.69; 95% CI [0.32, 1.48]). Incidence of adverse events and major adverse events were similar between groups. CONCLUSION: Factor XI inhibitors showed a significant reduction in the incidence of VTE and bleeding events among patients submitted to major orthopedic surgery.