Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
PharmacoEconomics
Published in: PharmacoEconomics 9/2014

01-09-2014 | Original Research Article

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

Authors: Antonio Gómez-Outes, Cristina Avendaño-Solá, Ana Isabel Terleira-Fernández, Emilio Vargas-Castrillón

Published in: PharmacoEconomics | Issue 9/2014

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
2.
Cohen AT, Agnelli G, Anderson FA, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98:756–64.PubMed
3.
Guijarro-Merino R, Montes-Santiago J, San Román-Terán CM. Epidemiología hospitalaria de la enfermedad tromboembólica venosa en España. Med Clin (Barc). 2008;131(Suppl. 2):2–9.CrossRef
4.
Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e278S–325S.
5.
National Institute for Health and Care Excellence (NICE). Guideline on venous thromboembolism. Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. Clinical guideline CG92, January 2010. http://​guidance.​nice.​org.​uk/​CG92. Accessed 13 Jul 2013.
6.
Arcelus JL, Monreal M, Caprini JA, et al. Clinical presentation and time-course of postoperative venous thromboembolism: results from the RIETE Registry. Thromb Haemost. 2008;99:546–51.PubMed
7.
8.
Craik JD, Cobb AG. Heparin-induced thrombocytopenia following hip and knee arthroplasty. Br J Haematol. 2013;161:255–61.PubMedCrossRef
9.
Gómez-Outes A, Lecumberri R, Pozo C, et al. New anticoagulants: focus on venous thromboembolism. Curr Vasc Pharmacol. 2009;7:309–29.PubMedCrossRef
10.
Ahrens I, Lip GY, Peter K. New oral anticoagulant drugs in cardiovascular disease. Thromb Haemost. 2010;104:49–60.PubMedCrossRef
11.
12.
13.
14.
Gómez-Outes A, Suárez-Gea ML, Blázquez-Pérez A, et al. Rivaroxaban versus enoxaparin after total knee arthroplasty. Lancet. 2009;374:682.PubMedCrossRef
15.
Gómez-Outes A, Suárez-Gea ML, Blázquez-Pérez A, et al. Will oral rivaroxaban improve clinically relevant outcomes and thromboprophylaxis management in the orthopedic patient? J Thromb Haemost. 2009;7:2149–50.PubMedCrossRef
16.
Gómez-Outes A, Terleira-Fernández AI, Suárez-Gea ML, et al. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons. BMJ. 2012;344:e3675.PubMedCentralPubMedCrossRef
17.
Sullivan SD, Kahn SR, Davidson BL, et al. Measuring the outcomes and pharmacoeconomic consequences of venous thromboembolism prophylaxis in major orthopaedic surgery. Pharmacoeconomics. 2003;21:477–96.PubMedCrossRef
18.
Davidson BL, Sullivan SD, Kahn SR, et al. The economics of venous thromboembolism prophylaxis: a primer for clinicians. Chest. 2003;124(6 Suppl):393S–6S.
19.
Monreal M, González-Rojas N, Vieta A, et al. Análisis económico de dabigatrán etexilato en prevención primaria del tromboembolismo venoso tras artroplastia total de cadera o rodilla. Pharmacoeconomics Spanish Research Articles. 2009;6:126–45.CrossRef
20.
Gómez-Cerezo JF, Gómez-Arrayás I, Suárez-Fernández C, et al. Análisis coste-efectividad de apixaban frente a dabigatrán en la prevención de la tromboembolia venosa en pacientes intervenidos de artroplastia total de rodilla o de cadera. Rev Esp Cir Ortop Traumatol. 2012;56:459–70.PubMed
21.
Brosa M, Monreal M, Piñol C. Análisis coste-efectividad de rivaroxabán en la prevención de la enfermedad tromboembólica venosa en España. Pharmacoeconomics Spanish Research Articles. 2012;9:33–44.CrossRef
22.
23.
Wee HL, Machin D, Loke WC, et al. Assessing differences in utility scores: a comparison of four widely used preference-based instruments. Value Health. 2007;10:256–65.PubMedCrossRef
24.
Wolowacz SE, Roskell NS, Maciver F, et al. Economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism after total knee and hip replacement surgery. Clin Ther. 2009;31:194–212.PubMedCrossRef
25.
Krauel K, Hackbarth C, Fürll B, et al. Heparin-induced thrombocytopenia: in vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies. Blood. 2012;119:1248–55.PubMedCrossRef
26.
Baroletti S, Piovella C, Fanikos J, et al. Heparin-induced thrombocytopenia (HIT): clinical and economic outcomes. Thromb Haemost. 2008;100:1130–5.PubMed
27.
Warwick D, Friedman RJ, Agnelli G, et al. Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry. J Bone Joint Surg Br. 2007;89:799–807.PubMedCrossRef
28.
Davies LM, Richardson GA, Cohen AT. Economic evaluation of enoxaparin as postdischarge prophylaxis for deep vein thrombosis (DVT) in elective hip surgery. Value Health. 2000;3:397–406.PubMedCrossRef
29.
Santamaría A, Juárez S, Reche A, et al. Low-molecular-weight heparin, bemiparin, in the outpatient treatment and secondary prophylaxis of venous thromboembolism in standard clinical practice: the ESFERA Study. Int J Clin Pract. 2006;60:518–25.PubMedCrossRef
30.
Rasanen P, Paavolainen P, Sintonen H, et al. Effectiveness of hip or knee replacement surgery in terms of quality-adjusted life years and costs. Acta Orthop. 2007;78:108–15.PubMedCrossRef
31.
Haentjens P, De Groote K, Annemans L. Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement: a cost-utility analysis. Arch Orthop Trauma Surg. 2004;124:507–17.PubMedCrossRef
32.
Hogg K, Kimpton M, Carrier M, et al. Estimating quality of life in acute venous thrombosis. JAMA Intern Med. 2013;173:1067–72.PubMedCrossRef
33.
34.
BOT PLUS 2.0: Base de datos del conocimiento sanitario [CD-ROM]. Madrid: Consejo General de Colegios Oficiales de Farmacéuticos; 2013.
35.
36.
Lecumberri R, Panizo E, Gomez-Guiu A, et al. Economic impact of an electronic alert system to prevent venous thromboembolism in hospitalised patients. J Thromb Haemost. 2011;9:1108–15.PubMedCrossRef
37.
38.
Resolución de 16 de junio de 2009, del Instituto Nacional de Gestión Sanitaria, sobre revisión de precios a aplicar por los centros sanitarios de las Ciudades Autónomas de Ceuta y Melilla por las asistencias prestadas en los supuestos cuyo importe ha de reclamarse a los terceros obligados al pago o a los usuarios sin derecho a la asistencia sanitaria de la Seguridad Social, así como por los servicios prestados por el Centro Nacional de Dosimetría y por la reproducción de documentos de la biblioteca de la entidad gestora. Boletín Oficial del Estado, lunes 22 de junio de 2009. http://​www.​boe.​es/​boe/​dias/​2009/​06/​22/​pdfs/​BOE-A-2009-10262.​pdf. Accessed 13 Jul 2013.
39.
40.
41.
Wilke T, Tesch S, Scholz A, et al. The costs of heparin-induced thrombocytopenia: a patient-based cost of illness analysis. J Thromb Haemost. 2009;7:766–73.PubMedCrossRef
42.
Kudrna J. New oral anticoagulants after total knee arthroplasty: clinical considerations for orthopaedic surgeons. Curr Orthop Pract. 2013;24:424–32.CrossRef
43.
Haut ER, Lau BD, Streiff MB. New oral anticoagulants for preventing venous thromboembolism. BMJ. 2012;344:e3820.PubMedCrossRef
44.
White RH, Romano PS, Zhou H, et al. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med. 1998;158:1525–31.PubMedCrossRef
45.
Prandoni P, Villalta S, Bagatella P, et al. The clinical course of deep-vein thrombosis: prospective long-term follow-up of 528 symptomatic patients. Haematologica. 1997;82:423–8.PubMed
46.
Masotti L, Di Napoli M, Godoy DA, et al. The practical management of intracerebral hemorrhage associated with oral anticoagulant therapy. Int J Stroke. 2011;6:228–40.PubMedCrossRef
47.
Sicras-Mainar A, De Salas-Cansado M, Ruiz-Antorán MB, et al. Utilización de recursos sanitarios y costes asociados al diagnóstico y tratamiento de cada episodio de trombosis venosa profunda y sangrado en pacientes intervenidos de cirugía ortopédica de cadera o rodilla. Rev Esp Cir Ortop Traumatol. 2012;56:341–53.PubMed
48.
Turpie AGG, Schmidt A, Lassen MR, et al. Rivaroxaban for thromboprophylaxis after total hip or knee replacement surgery: comparison of outcomes of the XAMOS and RECORD studies [abstract no. 500]. Blood (ASH annual meeting abstracts). 2012;120:Abstract 1160.
49.
Dahl OE, Quinlan DJ, Bergqvist D, et al. A critical appraisal of bleeding events reported in venous thromboembolism prevention trials of patients undergoing hip and knee arthroplasty. J Thromb Haemost. 2010;8:1966–75.PubMedCrossRef
50.
51.
Honorato J, Gómez-Outes A, Navarro-Quilis A, et al. Pharmacoeconomic analysis of bemiparin and enoxaparin as prophylaxis for venous thromboembolism in total knee replacement surgery. Pharmacoeconomics. 2004;22:885–94.PubMedCrossRef
Metadata
Title
Pharmacoeconomic Evaluation of Dabigatran, Rivaroxaban and Apixaban versus Enoxaparin for the Prevention of Venous Thromboembolism After Total Hip or Knee Replacement in Spain
Authors
Antonio Gómez-Outes
Cristina Avendaño-Solá
Ana Isabel Terleira-Fernández
Emilio Vargas-Castrillón
Publication date
01-09-2014
Publisher
Springer International Publishing
Published in
PharmacoEconomics / Issue 9/2014
Print ISSN: 1170-7690
Electronic ISSN: 1179-2027
DOI
https://doi.org/10.1007/s40273-014-0175-5

Other articles of this Issue 9/2014

PharmacoEconomics 9/2014 Go to the issue

Systematic Review

The Economic Burden of Head and Neck Cancer: A Systematic Literature Review

Commentary

Hospital-Based Health Technology Assessment: Insights from New Zealand

Leading Article

Hospital-Based Health Technology Assessment: Developments to Date

Review Article

Model-Based Cost-Effectiveness Analyses for the Treatment of Chronic Myeloid Leukaemia: A Review and Summary of Challenges

Original Research Article

Cost Effectiveness of Darunavir/ritonavir Combination Antiretroviral Therapy for Treatment-Naive Adults with HIV-1 Infection in Canada

Review Article

HTA Agencies Facing Model Biases: The Case of Type 2 Diabetes