Pharmacoeconomic Evaluation of Dabigatran, Rivaroxaban and Apixaban versus Enoxaparin for the Prevention of Venous Thromboembolism After Total Hip or Knee Replacement in Spain

Patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery are at high risk of developing venous thromboembolism (VTE). Thromboprophylaxis with low-molecular-weight heparin, such as enoxaparin, is standard of care in these patients. Recently, three direct oral anticoagulants (DOACs; dabigatran, rivaroxaban and apixaban), have been approved for this indication, but their cost effectiveness is still unclear as it has usually been extrapolated from surrogate venographic outcomes in clinical trials. To conduct a pharmacoeconomic evaluation of the DOACs versus subcutaneous (SC) enoxaparin for the prevention of VTE after THR or TKR surgery. A decision-tree model was developed using TreeAge Pro 2011 to compare the cost utility and cost effectiveness of the DOACs with SC enoxaparin, with separate models for THR and TKR over a 3-month postoperative time horizon from the perspective of the Spanish National Health System. The probabilities of events (symptomatic VTE, clinically relevant bleedings, heparin-induced thrombocytopenia and deaths) were derived from a systematic review and meta-analysis. We used local cost estimates (a,not sign2013) and utility values were obtained from the literature. We reported costs, quality-adjusted life-years (QALYs) and symptomatic VTE events. We conducted sensitivity analyses to evaluate parameter uncertainty. The average costs per 1,000 patients treated with enoxaparin were higher than costs incurred by dabigatran, rivaroxaban and apixaban in THR (a,not sign435,208 vs. a,not sign283,574, a,not sign257,900 and a,not sign212,472, respectively) and TKR (a,not sign336,550 vs. a,not sign219,856, a,not sign251,734 and a,not sign201,946, respectively), with cost savings ranging from a,not sign151,634 to a,not sign222,766 in THR, and from a,not sign84,816 to a,not sign134,604 in TKR. Cost differences were largely driven by differences in costs associated with drug administration. The average QALYs per 1,000 patients treated were very similar for enoxaparin, dabigatran, rivaroxaban and apixaban in THR (199.34, 198.83, 199.08 and 199.68, respectively) and TKR (198.95, 199.41, 198.75 and 199.97, respectively). Rivaroxaban (in TKR and THR) and apixaban (in THR) avoided additional symptomatic VTE events compared with enoxaparin. Sensitivity analyses generally supported the robustness of the analysis to changes in model parameters. Our model suggests, based on its underlying assumptions and data, that the DOACs are cost-saving alternatives to SC enoxaparin for the prevention of VTE after THR or TKR, in the Spanish healthcare setting.