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

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Abstract

Background

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.

Objective

To conduct a pharmacoeconomic evaluation of the DOACs versus subcutaneous (SC) enoxaparin for the prevention of VTE after THR or TKR surgery.

Methods

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 (€2013) 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.

Results

The average costs per 1,000 patients treated with enoxaparin were higher than costs incurred by dabigatran, rivaroxaban and apixaban in THR (€435,208 vs. €283,574, €257,900 and €212,472, respectively) and TKR (€336,550 vs. €219,856, €251,734 and €201,946, respectively), with cost savings ranging from €151,634 to €222,766 in THR, and from €84,816 to €134,604 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.

Conclusions

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.

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Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflicts of interest

Drs. Gómez-Outes, Terleira-Fernández and Vargas-Castrillón declare no conflicts of interest. Dr. Avendaño-Solá declares lectures fees from several companies, including Bayer and Pfizer, outside the submitted work.

Author contributions

Drs. Gómez-Outes and Avendaño-Solá conceived the study. Dr. Gómez-Outes designed the specific structure of and developed the global economic model. Drs. Gómez-Outes and Terleira-Fernández collected information regarding clinical outcomes, utilities, local costs and resource consumption. Dr. Gómez-Outes drafted the manuscript. Dr. Vargas-Castrillón supervised the study. All authors analysed and interpreted the data and critically revised the manuscript for important intellectual content. Drs. Gómez-Outes and Vargas-Castrillón are the guarantors. The contents of this study are solely the responsibility of the authors and do not necessarily represent the official view of their institutions or any other party.

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Authors and Affiliations

  1. Division of Pharmacology and Clinical Evaluation, Department of Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS), Parque Empresarial “Las Mercedes”, Edificio 8, C/Campezo 1, 28022, Madrid, Spain

    Antonio Gómez-Outes

  2. Department of Clinical Pharmacology, Hospital Puerta de Hierro, Majadahonda, Madrid, Spain

    Cristina Avendaño-Solá

  3. Department of Clinical Pharmacology, Hospital Clínico San Carlos, Madrid, Spain

    Ana Isabel Terleira-Fernández & Emilio Vargas-Castrillón

  4. Department of Pharmacology, Universidad Complutense, Madrid, Spain

    Ana Isabel Terleira-Fernández & Emilio Vargas-Castrillón

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  1. Antonio Gómez-Outes
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  2. Cristina Avendaño-Solá
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  3. Ana Isabel Terleira-Fernández
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  4. Emilio Vargas-Castrillón
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Correspondence to Antonio Gómez-Outes.

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Gómez-Outes, A., Avendaño-Solá, C., Terleira-Fernández, A.I. et al. Pharmacoeconomic Evaluation of Dabigatran, Rivaroxaban and Apixaban versus Enoxaparin for the Prevention of Venous Thromboembolism After Total Hip or Knee Replacement in Spain. PharmacoEconomics 32, 919–936 (2014). https://doi.org/10.1007/s40273-014-0175-5

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