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Introduction: Low molecular weight heparins are effective and have a good tolerability profile as first-line prophylaxis for venous thromboembolism (VTE) in major orthopaedic surgery. However, pharmacological inequivalence within the class could lead to differences in cost-effectiveness ratios.Objective: To quantify the potential economic impact of subcutaneous bemiparin sodium 3500 IU/day compared with enoxaparin sodium 40 mg/day as prophylaxis for VTE in patients undergoing total knee replacement (TKR) surgery, considering both in-hospital and post-discharge outcomes and costs during 6 weeks of postoperative follow-up.Methods: A cost-effectiveness analysis was performed using a decision modelling approach. The results were expressed in terms of costs and incremental cost effectiveness in Euro (2002 values). The treatment costs (hospital stay, physician services, drug administration) and costs incurred due to complications such as pulmonary embolism and/or proximal deep vein thrombosis, bleeding events, wound haematoma and thrombocytopenia were considered for this analysis. The target population comprised all adult patients undergoing TKR surgery included in a previous clinical trial (n = 381). The study was conducted in the setting of the Spanish National Health System. The time horizon chosen was 6 weeks.Results: Bemiparin provided cost savings of Euro144.48 per patient compared with enoxaparin when costs derived from treatment and complications during the 6-week postoperative period were considered (Euro4675.01 vs Euro4819.49). Pharmacy costs per patient were lower for bemiparin during hospital stay (Euro43.34 vs Euro50.20; difference, Euro-6.86) and for post-discharge prophylaxis (Euro68.63 vs Euro87.78; difference Euro-19.15). Bemiparin was calculated to avoid 42 additional VTE events per 1000 patients treated at 6 weeks. The incremental cost-effectiveness analysis indicated that bemiparin was dominant over enoxaparin, producing better outcomes and cost savings. The sensitivity analysis supported the cost effectiveness of bemiparin in all the ranges tested for complications and costs.Conclusions: Our model suggests, based on its underlying assumptions and data, that bemiparin may be more cost effective than enoxaparin for thromboprophylaxis in total knee replacement surgery in the Spanish healthcare setting. [ABSTRACT FROM AUTHOR]