Extended Treatment with Apixaban for Venous Thromboembolism Prevention in the Netherlands: Clinical and Economic Effects

Abstract

Background Dutch guidelines advise extended anticoagulant treatment with direct oral anticoagulants or vitamin K antagonists for patients with idiopathic venous thromboembolism (VTE) who do not have high bleeding risk.

Objectives The aim of this study was to analyze the economic effects of extended treatment of apixaban in the Netherlands, based on an updated and adapted previously published model.

Methods We performed a cost-effectiveness analysis simulating a population of 1,000 VTE patients. The base-case analysis compared extended apixaban treatment to no treatment after the first 6 months. Five additional scenarios were conducted to evaluate the effect of different bleeding risks and health care payers' perspective. The primary outcome of the model is the incremental cost-effectiveness ratio (ICER) in costs (€) per quality-adjusted life-year (QALY), with one QALY defined as 1 year in perfect health. To account for any influence of the uncertainties in the model, probabilistic and univariate sensitivity analyses were conducted. The treatment was considered cost-effective with an ICER less than €20,000/QALY, which is the most commonly used willingness-to-pay (WTP) threshold for preventive drugs in the Netherlands.

Results The model showed a reduction in recurrent VTE and no increase in major bleeding events for extended treatment in all scenarios. The base-case analysis showed an ICER of €9,653/QALY. The probability of being cost-effective for apixaban in the base-case was 70.0% and 91.4% at a WTP threshold of €20,000/QALY and €50,000/QALY, respectively.

Conclusion Extended treatment with apixaban is cost-effective for the prevention of recurrent VTE in Dutch patients.

Keywords

cost-effectiveness - venous thrombosis - apixaban - lifelong treatment - non–vitamin K oral anticoagulants

• References

• 1 Federation for Dutch Thrombosis Services (FNT). Medical report 2015. [cited December 1, 2016]; Available at: https://s3.eu-central-1.amazonaws.com/storage.topsite.nl/fnt.nl/uploads/docs/jaarverslagen/Algemeen_jaarverslag_2015.pdf . Accessed August 30, 2018
• 2 Prandoni P, Noventa F, Ghirarduzzi A. , et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007; 92 (02) 199-205
• 3 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest 2016; 149 (02) 315-352
• 4 Dutch Association of Internal Medicine. Richtlijn Antitrombotisch Beleid. [cited December 1, 2016]; Available at: https://internisten.nl/sites/internisten.nl/files/Richtlijn Antitrombotisch beleid_def.pdf . Accessed August 30, 2018
• 5 Oudega R, Van Weert H, Stoffers H. , et al. NHG-Standaard Diepe veneuze trombose. Huisarts Wet 2008; 51 (01) 24-37
• 6 Foundation for Pharmaceutical Statistics. Forse groei DOAC-gebruik zet ook dit jaar door. Pharm Weekbl 2017; 152 (18) 9
• 7 National Institute for Health and Care Excellence (NICE). Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. Guidance and guidelines. 2012 [cited December 1, 2016]. Available at: https://www.nice.org.uk/guidance/cg144 . Accessed August 30, 2018
• 8 Agnelli G, Buller HR, Cohen A. , et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (09) 799-808
• 9 Agnelli G, Buller HR, Cohen A. , et al; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368 (08) 699-708
• 10 de Jong LA, Dvortsin E, Janssen KJ, Postma MJ. Cost-effectiveness analysis for apixaban in the acute treatment and prevention of venous thromboembolism in the Netherlands. Clin Ther 2017; 39 (02) 288-302.e4
• 11 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 (04) 423-428
• 12 CHMP. Summary of Product Characteristics: Eliquis. [cited August 1, 2017]. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf . Accessed August 30, 2018
• 13 Linkins L, O’Donnell M, Julian JA, Kearon C. Intracranial and fatal bleeding according to indication for long-term oral anticoagulant therapy. J Thromb Haemost 2010; 8 (10) 2201-2207
• 14 Ariesen MJ, Claus SP, Rinkel GJE, Algra A. Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke 2003; 34 (08) 2060-2065
• 15 Miniati M, Monti S, Bottai M. , et al. Survival and restoration of pulmonary perfusion in a long-term follow-up of patients after acute pulmonary embolism. Medicine (Baltimore) 2006; 85 (05) 253-262
• 16 Flinterman LE, van Hylckama Vlieg A, Cannegieter SC, Rosendaal FR. Long-term survival in a large cohort of patients with venous thrombosis: incidence and predictors. PLoS Med 2012; 9 (01) e1001155
• 17 Ng ACC, Chung T, Yong AS. , et al. Long-term cardiovascular and noncardiovascular mortality of 1023 patients with confirmed acute pulmonary embolism. Circ Cardiovasc Qual Outcomes 2011; 4 (01) 122-128
• 18 Stevanović J, de Jong LA, Kappelhoff BS, Dvortsin EP, Voorhaar M, Postma MJ. Dabigatran for the treatment and secondary prevention of venous thromboembolism: a cost-effectiveness analysis for the Netherlands. PLoS One 2016; 11 (10) e0163550
• 19 Statistics Netherlands. Life-expectancy: gender and age per year from 1950. [cited October 1, 2015]. Available at: http://statline.cbs.nl/Statweb/publication/?DM=SLNL&PA=37360ned&D1=0&D2=a&D3=20-99&D4=l&HDR=G1,T&STB=G2,G3&VW=T . Accessed August 30, 2018
• 20 Hakkaart-van Roijen L, van der Linden N, Bouwmans C, Kanters T, Swan Tan S. Kostenhandleiding: Methodologie van kostenonderzoek en referentieprijzen voor economische evaluaties in de gezondheidszorg. Published by: Zorginstituut Ned. 2016;1–120. Available at: www.zorginstituutnederland.nl/publicaties/publicatie/2016/02/29/richtlijn-voor-het-uitvoeren-van-economische-evaluaties-in-de-gezondheidszorg
• 21 The National Health Care Institute Netherlands (ZIN). [cited December 1, 2016]. Available at: http://www.medicijnkosten.nl
• 22 Dutch Healthcare Authority (NZa). Tarieven & Prestaties: Tarieventable DBC-zorgproducten en overige producten. 2012 [cited December 1, 2016]. Available at: https://puc.overheid.nl/nza/zoeken/resultaat/s/2/p/1/gdlv/1/g/1/srt/tarieven_en_prestaties/ . Accessed August 30, 2018
• 23 National Institute for Health and Care Excellence (NICE). Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism. 2013 [cited September 1, 2015]; Available at: https://www.nice.org.uk/guidance/ta261/resources/venous-thromboembolism-treatment-and-long-term-secondary-prevention-rivaroxaban-final-appraisal-determination-guidance2 . Accessed August 30, 2018
• 24 National Institute for Health and Care Excellence (NICE). Final appraisal determination – Rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism Rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism. 2013 [cited September 1, 2015]; Available at: https://www.nice.org.uk/guidance/TA287/documents/pulmonary-embolism-acute-treatment-vte-prevention-rivaroxaban-final-appraisal-determination-document2 . Accessed August 30, 2018
• 25 Stevanović J, Pompen M, Le HH, Rozenbaum MH, Tieleman RG, Postma MJ. Economic evaluation of apixaban for the prevention of stroke in non-valvular atrial fibrillation in the Netherlands. PLoS One 2014; 9 (08) e103974
• 26 Ten Cate-Hoek AJ, Toll DB, Büller HR. , et al. Cost-effectiveness of ruling out deep venous thrombosis in primary care versus care as usual. J Thromb Haemost 2009; 7 (12) 2042-2049
• 27 M Versteegh M, , M Vermeulen K, , M A A Evers S, de Wit GA, Prenger R, , A Stolk E. Dutch tariff for the five-level version of EQ-5D. Value Health 2016; 19 (04) 343-352
• 28 Drummond M, Sculpher M, Torrance G, O'Brien B, Stoddart G. Methods for the Economic Evaluation of Health Care Programmers. 3rd ed. New York, NY: Oxford University Press; 2005
• 29 Lanitis T, Hamilton M, Quon P, Browne C, Masseria C, Cohen AT. Cost-effectiveness of apixaban compared to low molecular weight heparin/edoxaban for treatment and prevention of recurrent venous thromboembolism. Value Health 2015; 18 (07) A375-A376
• 30 Ministry of Health W and S (VWS). Zinnige en duurzame zorg. 2006 [cited August 1, 2017]. Available at: https://www.raadrvs.nl/uploads/docs/Advies_-_Zinnige_en_duurzame_zorg.pdf . Accessed August 30, 2018
• 31 Verhoef TI, Redekop WK, Hasrat F, de Boer A, Maitland-van der Zee AH. Cost effectiveness of new oral anticoagulants for stroke prevention in patients with atrial fibrillation in two different European healthcare settings. Am J Cardiovasc Drugs 2014; 14 (06) 451-462
• 32 Elías I, Oyagüez I, Alvarez-Sala LA. , et al. Cost-effectiveness analysis of apixaban compared to low-molecular weight heparins and vitamin k antagonists for treatment and secondary prevention of venous thromboembolism. Farm Hosp 2016; 40 (03) 187-208
• 33 Statistics Netherlands (CBS). Consumentenprijsindex; vanaf 1963. [cited December 1, 2016]. Available at: http://statline.cbs.nl/StatWeb/publication/?DM=SLNL&PA=70936ned&D1=0&D2=623,636,649,662&HDR=T&STB=G1&VW=T . Accessed August 30, 2018
• 34 Lefebvre P, Coleman CI, Bookhart BK. , et al. Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism. J Med Econ 2014; 17 (01) 52-64
• 35 Seaman CD, Smith KJ, Ragni MV. Cost-effectiveness of rivaroxaban versus warfarin anticoagulation for the prevention of recurrent venous thromboembolism: a U.S. perspective. Thromb Res 2013; 132 (06) 647-651