Real-world cost-effectiveness of rivaroxaban compared with vitamin K antagonists in the context of stroke prevention in atrial fibrillation in France

Autoři: Kevin Bowrin aff001;  Jean-Baptiste Briere aff002;  Laurent Fauchier aff003;  Craig Coleman aff004;  Aurélie Millier aff005;  Mondher Toumi aff006;  Emilie Clay aff005;  Pierre Levy aff007
Působiště autorů: Bayer Plc, Reading, England, United Kingdom aff001;  Bayer AG, Berlin, Germany aff002;  Cardiologie, Centre Hospitalier Universitaire Trousseau et Université François Rabelais, Tours, France aff003;  University of Connecticut, School of Pharmacy, Storrs, Connecticut, United States of America aff004;  Creativ-Ceutical, Paris, France aff005;  Aix-Marseille University, Marseille, France aff006;  Université Paris-Dauphine, PSL Research University, LEDa-LEGOS, Paris, France aff007
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article



The objective was to assess the real-world cost-effectiveness of rivaroxaban, versus vitamin K antagonists (VKAs), for stroke prevention in patients with atrial fibrillation (AF) from a French national health insurance perspective.


A Markov model was developed with a lifetime horizon and cycle length of 3 months. All inputs were drawn from real-world evidence (RWE) studies: data on baseline patient characteristics at model entry were obtained from a French RWE study, clinical event rates as well as persistence rates for the VKA treatment arm were estimated from a variety of RWE studies, and a meta-analysis provided comparative effectiveness for rivaroxaban compared to VKA. Model outcomes included costs (drug costs, clinical event costs, and VKA monitoring costs), quality-adjusted life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers.


In the base-case analysis, the incremental total cost was €714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The resulting incremental cost/QALY and incremental cost/LY were €6,006 and €4,586, respectively. The results were more sensitive to the inclusion of treatment-specific utility decrements and clinical event rates.


Although there is no official willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA in French patients with AF from a national insurance perspective.

Klíčová slova:

Atrial fibrillation – Cardiac rehabilitation – Cost-effectiveness analysis – France – Ischemic stroke – Metaanalysis – Myocardial infarction – vitamin K


1. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr., et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):2071–104. Epub 2014/04/01. doi: 10.1161/CIR.0000000000000040 24682348.

2. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg. 2016;50(5):e1–e88. Epub 2016/09/25. doi: 10.1093/ejcts/ezw313 27663299.

3. Kakkar A, Mueller I, Bassand J, Fitzmaurice D, Goldhaber S, Goto S, et al. Risk profiles and antithrombotic treatment of patients newly diagnosed with atrial fibrillation at risk of stroke: perspectives from the International, observational, prospective GARFIELD registry. PLoS One. 2013;8(5):e63479. doi: 10.1371/journal.pone.0063479 23704912

4. Lopes RD, Crowley MJ, Shah BR, Melloni C, Wood KA, Chatterjee R, et al. AHRQ Comparative Effectiveness Reviews. Stroke Prevention in Atrial Fibrillation. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013.

5. Savelieva I, Camm AJ. Practical considerations for using novel oral anticoagulants in patients with atrial fibrillation. Clin Cardiol. 2014;37(1):32–47. Epub 2013/11/21. doi: 10.1002/clc.22204 24254991.

6. Verpillat P, Dorey J, Guilhaume-Goulant C, Dabbous F, Aballea S. Ischemic stroke management in West Scotland: a chart review. J Mark Access Health Policy. 2015;3. Epub 2015/01/01. doi: 10.3402/jmahp.v3.26339 27123179; PubMed Central PMCID: PMC4802692.

7. Stroke Alliance For Europe (SAFE). Burden of stroke report launched in EU parliament. In: London KsC, editor. 2017.

8. Blommestein HM, Franken MG, Uyl-de Groot CA. A practical guide for using registry data to inform decisions about the cost effectiveness of new cancer drugs: lessons learned from the PHAROS registry. Pharmacoeconomics. 2015;33(6):551–60. doi: 10.1007/s40273-015-0260-4 25644460; PubMed Central PMCID: PMC4445765.

9. Annemans L AM, Kubin M. Real-life data: a growing need. ISPOR Connections. 2007;13(5):8–13.

10. Coleman CI, Briere JB, Fauchier L, Levy P, Bowrin K, Toumi M, et al. Meta-analysis of real-world evidence comparing non-vitamin K antagonist oral anticoagulants with vitamin K antagonists for the treatment of patients with non-valvular atrial fibrillation. J Mark Access Health Policy. 2019;7(1):1574541. doi: 10.1080/20016689.2019.1574541 30774786; PubMed Central PMCID: PMC6366429.

11. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91. doi: 10.1056/NEJMoa1009638 21830957

12. Bayer Plc. Single technology appraisal (STA) of rivaroxaban (Xarelto®). National Institute for Health and Clinical Excellence; 2011.

13. Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med. 2003;349(11):1019–26. doi: 10.1056/NEJMoa022913 12968085

14. Coleman CI, Tangirala M, Evers T. Treatment persistence and discontinuation with rivaroxaban, dabigatran, and warfarin for stroke prevention in patients with non-valvular atrial fibrillation in the United States. PLoS One. 2016;11(6):e0157769. doi: 10.1371/journal.pone.0157769 27327275; PubMed Central PMCID: PMC4915663.

15. Collings SL, Vannier-Moreau V, Johnson ME, Stynes G, Lefevre C, Maguire A, et al. Initiation and continuation of oral anticoagulant prescriptions for stroke prevention in non-valvular atrial fibrillation: A cohort study in primary care in France. Arch Cardiovasc Dis. 2018;111(5):370–9. doi: 10.1016/j.acvd.2017.10.003 29398546.

16. Fauchier L, Samson A, Chaize G, Gaudin AF, Vainchtock A, Bailly C, et al. Cause of death in patients with atrial fibrillation admitted to French hospitals in 2012: a nationwide database study. Open Heart. 2015;2(1):e000290. doi: 10.1136/openhrt-2015-000290 26688739; PubMed Central PMCID: PMC4680587.

17. Lip G, Pan X, Kamble S, Kawabata H, Mardekian J, Masseria C, et al. Real world comparison of major bleeding risk among non-valvular atrial fibrillation patients newly initiated on apixaban, dabigatran, rivaroxaban or warfarin. Eur Heart J. 2015;Anticoagulation and atrial fibrillation III(P6217):1085.

18. Blin P, Philippe F, Bouee S, Laurendeau C, Torreton E, Gourmelin J, et al. Outcomes following acute hospitalised myocardial infarction in France: An insurance claims database analysis. Int J Cardiol. 2016;219:387–93. doi: 10.1016/j.ijcard.2016.06.102 Epub@2016 Jun 23.:387–93. 27372604

19. Cotte FE, Chaize G, Kachaner I, Gaudin AF, Vainchtock A, Durand-Zaleski I. Incidence and cost of stroke and hemorrhage in patients diagnosed with atrial fibrillation in France. J Stroke Cerebrovasc Dis. 2014;23(2):e73–e83. doi: 10.1016/j.jstrokecerebrovasdis.2013.08.022 24119623

20. Kongnakorn T, Lanitis T, Annemans L, Thijs V, Goethals M, Marbaix S, et al. Stroke and systemic embolism prevention in patients with atrial fibrillation in Belgium: comparative cost effectiveness of new oral anticoagulants and warfarin. Clin Drug Investig. 2015;35(2):109–19. doi: 10.1007/s40261-014-0253-7 25511639

21. Luengo-Fernandez R, Gray AM, Bull L, Welch S, Cuthbertson F, Rothwell PM, et al. Quality of life after TIA and stroke: ten-year results of the Oxford Vascular Study. Neurology. 2013;81(18):1588–95. doi: 10.1212/WNL.0b013e3182a9f45f 24107865; PubMed Central PMCID: PMC3806919.

22. Pockett RD, McEwan P, Beckham C, Shutler S, Martin S, Yousef Z, et al. Health utility in patients following cardiovascular events. Value Health. 2014;17(7):A328.

23. CNAMTS. Fiche—PREVISCAN 20 MG (FLUINDIONE) 1 Boîte de 30, comprimés quadrisécables. Available from:


25. Lanitis T, Cotte FE, Gaudin AF, Kachaner I, Kongnakorn T, Durand-Zaleski I. Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin. J Med Econ. 2014;17(8):587–98. doi: 10.3111/13696998.2014.923891 24831811.

26. Cotte FE, Chaize G, Gaudin AF, Samson A, Vainchtock A, Fauchier L. Burden of stroke and other cardiovascular complications in patients with atrial fibrillation hospitalized in France. Europace. 2016;18(4):501–7. doi: 10.1093/europace/euv248 26718532; PubMed Central PMCID: PMC4865060.

27. Haute Autorité de santé (HAS). Choices in Methods for Economic Evaluation. 2012.

28. Lip GY, Banerjee A, Lagrenade I, Lane DA, Taillandier S, Fauchier L. Assessing the risk of bleeding in patients with atrial fibrillation: the Loire Valley Atrial Fibrillation project. Circ Arrhythm Electrophysiol. 2012;5(5):941–8. CIRCEP.112.972869 [pii]; doi: 10.1161/CIRCEP.112.972869 22923275

29. Wang TJ, Massaro JM, Levy D, Vasan RS, Wolf PA, D'Agostino RB, et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. JAMA. 2003;290(8):1049–56. doi: 10.1001/jama.290.8.1049 12941677

30. Camm AJ, Amarenco P, Haas S, Hess S, Kirchhof P, Kuhls S, et al. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J. 2016;37(14):1145–53. doi: 10.1093/eurheartj/ehv466 26330425; PubMed Central PMCID: PMC4823634.

31. Dewilde S, Thijs V, Annemans L, Peeters A, Belgian Stroke Council NP. Quality of life decrements after stroke. Value Health. 2014;17(7):A331. doi: 10.1016/j.jval.2014.08.622 27200574.

32. Cohen A DJ, Durand-Zaleski I, Bouée S, Le Heuzey JY; EPHA Investigators. Characteristics and management of outpatients with history of or current atrial fibrillation: the observational French EPHA study. Arch Cardiovasc Dis 2010;103(6–7):376–87. doi: 10.1016/j.acvd.2010.06.001 Epub 2010 Jul 22. 20800801

33. Dallongeville J, Ansolabehere X, Karusisi N, Maurel F, Van Ganse E, Le Heuzey JY. Real-life cost of vitamin K antagonist treatment in patients with non-valvular atrial fibrillation in France in 2013. J Med Econ. 2017;20(9):974–81. doi: 10.1080/13696998.2017.1352508 28682153.

34. Sherwood A, Maurel F, Colin X. Appraising the cost of physician visits and technical procedures In France in the age of open data. Value Health. 2015;18(7):A531–A2. doi: 10.1016/j.jval.2015.09.1655

35. Gage BF, Cardinalli AB, Owens DK. The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch Intern Med. 1996;156(16):1829–36. 8790077.

36. Bassand JP, Accetta G, Camm AJ, Cools F, Fitzmaurice DA, Fox KA, et al. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. Eur Heart J. 2016;37(38):2882–9. doi: 10.1093/eurheartj/ehw233 27357359; PubMed Central PMCID: PMC5070447.

37. Limone BL, Baker WL, Kluger J, Coleman CI. Novel anticoagulants for stroke prevention in atrial fibrillation: a systematic review of cost-effectiveness models. PLoS One. 2013;8(4):e62183. Epub 2013/04/30. doi: 10.1371/journal.pone.0062183 23626785; PubMed Central PMCID: PMC3633898.

38. Chevalier J, Delaitre O, Hammes F, de Pouvourville G. Cost-effectiveness of dabigatran versus vitamin K antagonists for the prevention of stroke in patients with atrial fibrillation: a French payer perspective. Arch Cardiovasc Dis. 2014;107(6–7):381–90. doi: 10.1016/j.acvd.2014.04.009 24973113.

39. de Jong LA, Gout-Zwart JJ, van den Bosch M, Koops M, Postma MJ. Rivaroxaban for non-valvular atrial fibrillation and venous thromboembolism in the Netherlands: a real-world data based cost-effectiveness analysis. J Med Econ. 2019;22(4):306–18. doi: 10.1080/13696998.2018.1563404 30614320.

40. Bennaghmouch N, de Veer A, Mahmoodi BK, Jofre-Bonet M, Lip GYH, Bode K, et al. Economic evaluation of the use of non-vitamin K oral anticoagulants in patients with atrial fibrillation on antiplatelet therapy: a modelling analysis using the healthcare system in the Netherlands. Eur Heart J Qual Care Clin Outcomes. 2019;5(2):127–35. doi: 10.1093/ehjqcco/qcy030 30016398.

41. Peng S, Deger KA, Ustyugova A, Gandhi P, Qiao N, Wang C, et al. Cost-effectiveness analysis of dabigatran versus rivaroxaban for stroke prevention in patients with non-valvular atrial fibrillation using real-world evidence in elderly US Medicare beneficiaries. Curr Med Res Opin. 2018;34(1):55–63. doi: 10.1080/03007995.2017.1375470 28862479.

42. Zhao YJ, Lin L, Zhou HJ, Tan KT, Chew AP, Foo CG, et al. Cost-effectiveness modelling of novel oral anticoagulants incorporating real-world elderly patients with atrial fibrillation. Int J Cardiol. 2016;220:794–801. doi: 10.1016/j.ijcard.2016.06.087 27400183.

43. Bowrin K, Briere JB, Levy P, Millier A, Clay E, Toumi M. Cost-effectiveness analyses using real-world data: an overview of the literature. J Med Econ. 2019:1–9. doi: 10.1080/13696998.2019.1588737 30816067.

44. Briere JB, Bowrin K, Taieb V, Millier A, Toumi M, Coleman C. Meta-analyses using real-world data to generate clinical and epidemiological evidence: a systematic literature review of existing recommendations. Curr Med Res Opin. 2018:1–6. doi: 10.1080/03007995.2018.1524751 30217138.

45. Levy P, Briere JB, Bowrin K, Millier A, editors. Challenges in the use of real-world evidence for pharmacoeconomic modelling. International Society for Pharmacoeconomics and Outcomes Research; 2018 10–14 November 2018; Barcelona, Spain.

Článek vyšel v časopise


2020 Číslo 1
Nejčtenější tento týden