nach oben

PharmacoEconomics

Erschienen in:

01.04.2015 | Original Research Article

Cost Effectiveness of Novel Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation Depending on the Quality of Warfarin Anticoagulation Control

verfasst von: Andrej Janzic, Mitja Kos

Erschienen in: PharmacoEconomics | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

Background

Vitamin K antagonists, such as warfarin, are standard treatments for stroke prophylaxis in patients with atrial fibrillation. Patient outcomes depend on quality of warfarin management, which includes regular monitoring and dose adjustments. Recently, novel oral anticoagulants (NOACs) that do not require regular monitoring offer an alternative to warfarin. The aim of this study was to evaluate whether cost effectiveness of NOACs for stroke prevention in atrial fibrillation depends on the quality of warfarin control.

Methods

We developed a Markov decision model to simulate warfarin treatment outcomes in relation to the quality of anticoagulation control, expressed as percentage of time in the therapeutic range (TTR). Standard treatment with adjusted-dose warfarin and improved anticoagulation control by genotype-guided dosing were compared with dabigatran, rivaroxaban, apixaban and edoxaban. The analysis was performed from the Slovenian healthcare payer perspective using 2014 costs.

Results

In the base case, the incremental cost-effectiveness ratio for apixaban, dabigatran and edoxaban was below the threshold of €25,000 per quality-adjusted life-years compared with adjusted-dose warfarin with a TTR of 60 %. The probability that warfarin was a cost-effective option was around 1 %. This percentage rises as the quality of anticoagulation control improves. At a TTR of 70 %, warfarin was the preferred treatment in half the iterations.

Conclusion

The cost effectiveness of NOACs for stroke prevention in patients with nonvalvular atrial fibrillation who are at increased risk for stroke is highly sensitive to warfarin anticoagulation control. NOACs are more likely to be cost-effective options in settings with poor warfarin management than in settings with better anticoagulation control, where they may not represent good value for money.

Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31(19):2369–429. doi:10.1093/eurheartj/ehq278.CrossRefPubMed

Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983–8.CrossRefPubMed

Dulli DA, Stanko H, Levine RL. Atrial fibrillation is associated with severe acute ischemic stroke. Neuroepidemiology. 2003;22(2):118–23 (68743 [pii]).CrossRefPubMed

Slot KB, Berge E, Dorman P, Lewis S, Dennis M, Sandercock P. Impact of functional status at six months on long term survival in patients with ischaemic stroke: prospective cohort studies. BMJ. 2008;336(7640):376–9. doi:10.1136/bmj.39456.688333.BE.CrossRefPubMedCentralPubMed

Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–67 (146/12/857 [pii]).CrossRefPubMed

van Walraven C, Hart RG, Singer DE, Laupacis A, Connolly S, Petersen P, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA. 2002;288(19):2441–8 (jcc20007 [pii]).CrossRefPubMed

Jones M, McEwan P, Morgan CL, Peters JR, Goodfellow J, Currie CJ. Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population. Heart. 2005;91(4):472–7. doi:10.1136/hrt.2004.042465.CrossRefPubMedCentralPubMed

Connolly SJ, Pogue J, Eikelboom J, Flaker G, Commerford P, Franzosi MG, et al. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation. 2008;118(20):2029–37. doi:10.1161/CIRCULATIONAHA.107.750000.CrossRefPubMed

White HD, Gruber M, Feyzi J, Kaatz S, Tse HF, Husted S, et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med. 2007;167(3):239–45. doi:10.1001/archinte.167.3.239.CrossRefPubMed

10.

Boulanger L, Kim J, Friedman M, Hauch O, Foster T, Menzin J. Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with non-valvular atrial fibrillation in clinical practice. Int J Clin Pract. 2006;60(3):258–64. doi:10.1111/j.1368-5031.2006.00790.x.CrossRefPubMed

11.

Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010;376(9745):975–83. doi:10.1016/S0140-6736(10)61194-4.CrossRefPubMed

12.

Pengo V, Pegoraro C, Cucchini U, Iliceto S. Worldwide management of oral anticoagulant therapy: the ISAM study. J Thromb Thrombolysis. 2006;21(1):73–7. doi:10.1007/s11239-006-5580-y.CrossRefPubMed

13.

Van Spall HG, Wallentin L, Yusuf S, Eikelboom JW, Nieuwlaat R, Yang S, et al. Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: an analysis of patients receiving warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial. Circulation. 2012;126(19):2309–16. doi:10.1161/CIRCULATIONAHA.112.101808.CrossRefPubMed

14.

van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006;129(5):1155–66. doi:10.1378/chest.129.5.1155.CrossRefPubMed

15.

Ansell J, Jacobson A, Levy J, Voller H, Hasenkam JM. Guidelines for implementation of patient self-testing and patient self-management of oral anticoagulation. International consensus guidelines prepared by International Self-Monitoring Association for Oral Anticoagulation. Int J Cardiol. 2005;99(1):37–45. doi:10.1016/j.ijcard.2003.11.008.CrossRefPubMed

16.

Anderson JL, Horne BD, Stevens SM, Woller SC, Samuelson KM, Mansfield JW, et al. A randomized and clinical effectiveness trial comparing two pharmacogenetic algorithms and standard care for individualizing warfarin dosing (CoumaGen-II). Circulation. 2012;125(16):1997–2005. doi:10.1161/CIRCULATIONAHA.111.070920.CrossRefPubMed

17.

You JH, Tsui KK, Wong RS, Cheng G. Potential clinical and economic outcomes of CYP2C9 and VKORC1 genotype-guided dosing in patients starting warfarin therapy. Clin Pharmacol Ther. 2009;86(5):540–7. doi:10.1038/clpt.2009.104.CrossRefPubMed

18.

Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, et al. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013;369(24):2294–303. doi:10.1056/NEJMoa1311386.CrossRefPubMed

19.

Yip VL, Pirmohamed M. Expanding role of pharmacogenomics in the management of cardiovascular disorders. Am J Cardiovasc Drugs. 2013;13(3):151–62. doi:10.1007/s40256-013-0024-5.CrossRefPubMed

20.

Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013;369(24):2283–93. doi:10.1056/NEJMoa1310669.CrossRefPubMedCentralPubMed

21.

Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51. doi:10.1056/NEJMoa0905561.CrossRefPubMed

22.

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.CrossRefPubMed

23.

Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92. doi:10.1056/NEJMoa1107039.CrossRefPubMed

24.

Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104. doi:10.1056/NEJMoa1310907.CrossRefPubMed

25.

Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285(22):2864–70 (joc01974 [pii]).CrossRefPubMed

26.

Poli D, Antonucci E, Marcucci R, Fatini C, Alterini B, Mannini L, et al. Risk of bleeding in very old atrial fibrillation patients on warfarin: relationship with ageing and CHADS2 score. Thromb Res. 2007;121(3):347–52. doi:10.1016/j.thromres.2007.05.014.CrossRefPubMed

27.

Oldgren J, Alings M, Darius H, Diener HC, Eikelboom J, Ezekowitz MD, et al. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern Med. 2011;155(10):660–7, W204. doi:10.7326/0003-4819-155-10-201111150-00004.

28.

FDA—Center for Drug Evaluation and Research. Dabigatran Clinical Review. NDA 022-512.2010 August 25, 2010.

29.

FDA—Center for Drug Evaluation and Research. Apixaban Clinical Review. NDA 202-155.2012 December 17, 2012.

30.

Johnson & Johnson Pharmaceutical Research and Development. Advisory Committee Briefing Document: BAY 59-7939 (Rivaroxaban) 2010, 05 August 2011.

31.

Hankey GJ, Patel MR, Stevens SR, Becker RC, Breithardt G, Carolei A, et al. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF. Lancet Neurol. 2012;11(4):315–22. doi:10.1016/S1474-4422(12)70042-X.CrossRefPubMed

32.

Easton JD, Lopes RD, Bahit MC, Wojdyla DM, Granger CB, Wallentin L, et al. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial. Lancet Neurol. 2012;11(6):503–11. doi:10.1016/S1474-4422(12)70092-3.CrossRefPubMed

33.

Huybrechts KF, Caro JJ, Xenakis JJ, Vemmos KN. The prognostic value of the modified Rankin Scale score for long-term survival after first-ever stroke. Results from the Athens Stroke Registry. Cerebrovasc Dis. 2008;26(4):381–7. doi:10.1159/000151678.CrossRefPubMed

34.

Gallagher AM, Setakis E, Plumb JM, Clemens A, van Staa TP. Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Thromb Haemost. 2011;106(5):968–77. doi:10.1160/TH11-05-0353.CrossRefPubMed

35.

Van Den Ham HA, Klungel OH, Leufkens HG, Van Staa TP. The patterns of anticoagulation control and the risk of stroke, bleeding and mortality in patients with non-valvular atrial fibrillation. J Thromb Haemost. 2013;11(1):107–15. doi:10.1111/jth.12041.CrossRef

36.

Herman D, Locatelli I, Grabnar I, Peternel P, Stegnar M, Mrhar A, et al. Influence of CYP2C9 polymorphisms, demographic factors and concomitant drug therapy on warfarin metabolism and maintenance dose. Pharmacogenomics J. 2005;5(3):193–202. doi:10.1038/sj.tpj.6500308.CrossRefPubMed

37.

Caraco Y, Blotnick S, Muszkat M. CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study. Clin Pharmacol Ther. 2008;83(3):460–70. doi:10.1038/sj.clpt.6100316.CrossRefPubMed

38.

Tengs TO, Lin TH. A meta-analysis of quality-of-life estimates for stroke. Pharmacoeconomics. 2003;21(3):191–200 (210304 [pii]).CrossRefPubMed

39.

Sullivan PW, Ghushchyan V. Preference-Based EQ-5D index scores for chronic conditions in the United States. Med Decis Making. 2006;26(4):410–20. doi:10.1177/0272989X06290495.CrossRefPubMedCentralPubMed

40.

Pink J, Lane S, Pirmohamed M, Hughes DA. Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses. BMJ. 2011;343:d6333. doi:10.1136/bmj.d6333.CrossRefPubMedCentralPubMed

41.

Rognoni C, Marchetti M, Quaglini S, Liberato NL. Edoxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis. J Thromb Thrombolysis. 2014. doi:10.1007/s11239-014-1104-3.

42.

Nerat T, Kos M. Burden of type 2 diabetes from the healthcare payer perspective in Slovenia. Zdrav Varst. 2013;52(3):162–80. doi:10.2478/sjph-2013-0018.

43.

Mavri A, editor. Priročnik za uporabo novih peroralnih antikoagulacijskih zdravil v klinični praksi. Slovensko zdravniško društvo: Ljubljana; 2012.

44.

Mavri A, Tratar G. Kakovost vodenja antikoagulacijskega zdravljenja v Sloveniji. ISIS. 2007;16(10):56–9.

45.

Mueller S, Pfannkuche M, Breithardt G, Bauersachs R, Maywald U, Kohlmann T, et al. The quality of oral anticoagulation in general practice in patients with atrial fibrillation. Eur J Intern Med. 2014;25(3):247–54. doi:10.1016/j.ejim.2013.12.013.CrossRefPubMed

46.

Verhoef TI, Redekop WK, van Schie RM, Bayat S, Daly AK, Geitona M, et al. Cost-effectiveness of pharmacogenetics in anticoagulation: international differences in healthcare systems and costs. Pharmacogenomics. 2012;13(12):1405–17. doi:10.2217/pgs.12.124.CrossRefPubMed

47.

Wieloch M, Sjalander A, Frykman V, Rosenqvist M, Eriksson N, Svensson PJ. Anticoagulation control in Sweden: reports of time in therapeutic range, major bleeding, and thrombo-embolic complications from the national quality registry AuriculA. Eur Heart J. 2011;32(18):2282–9. doi:10.1093/eurheartj/ehr134.CrossRefPubMed

48.

Kasmeridis C, Apostolakis S, Ehlers L, Rasmussen LH, Boriani G, Lip GY. Cost effectiveness of treatments for stroke prevention in atrial fibrillation: focus on the novel oral anticoagulants. Pharmacoeconomics. 2013;31(11):971–80. doi:10.1007/s40273-013-0090-1.CrossRefPubMed

49.

Kansal AR, Zheng Y, Pokora T, Sorensen SV. Cost-effectiveness of new oral anticoagulants in the prevention of stroke in patients with atrial fibrillation. Best Pract Res Clin Haematol. 2013;26(2):225–37. doi:10.1016/j.beha.2013.07.012.CrossRefPubMed

50.

Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS, et al. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med. 2011;154(1):1–11. doi:10.7326/0003-4819-154-1-201101040-00289.CrossRefPubMed

51.

Choudhry NK, Anderson GM, Laupacis A, Ross-Degnan D, Normand SL, Soumerai SB. Impact of adverse events on prescribing warfarin in patients with atrial fibrillation: matched pair analysis. BMJ. 2006;332(7534):141–5. doi:10.1136/bmj.38698.709572.55.CrossRefPubMedCentralPubMed

52.

Devereaux PJ, Anderson DR, Gardner MJ, Putnam W, Flowerdew GJ, Brownell BF, et al. Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. BMJ. 2001;323(7323):1218–22.CrossRefPubMedCentralPubMed

53.

Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med. 2004;164(8):880–4. doi:10.1001/archinte.164.8.880.CrossRefPubMed

54.

Howard R, Leathart JB, French DJ, Krishan E, Kohnke H, Wadelius M, et al. Genotyping for CYP2C9 and VKORC1 alleles by a novel point of care assay with HyBeacon(R) probes. Clin Chim Acta. 2011;412(23–24):2063–9. doi:10.1016/j.cca.2011.07.013.CrossRefPubMed

Titel: Cost Effectiveness of Novel Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation Depending on the Quality of Warfarin Anticoagulation Control
verfasst von: Andrej Janzic
Mitja Kos
Publikationsdatum: 01.04.2015
Verlag: Springer International Publishing
Erschienen in: PharmacoEconomics / Ausgabe 4/2015
Print ISSN: 1170-7690
Elektronische ISSN: 1179-2027
DOI: https://doi.org/10.1007/s40273-014-0246-7

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Cost Effectiveness of Novel Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation Depending on the Quality of Warfarin Anticoagulation Control

Abstract

Background

Methods

Results

Conclusion

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Background

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2015

Cost-of-Illness Studies for Bipolar Disorder: Systematic Review of International Studies

An Educational Review of the Statistical Issues in Analysing Utility Data for Cost-Utility Analysis

Predicting the Impact of Adverse Events and Treatment Duration on Medical Resource Utilization-Related Costs in Hepatitis C Genotype 1 Treatment-Naïve Patients Receiving Antiviral Therapy

Systematic Review of Cost-Effectiveness Analyses of Treatments for Psoriasis

Cost Effectiveness of Dabrafenib as a First-Line Treatment in Patients with BRAF V600 Mutation-Positive Unresectable or Metastatic Melanoma in Canada

Cost-Effectiveness Analysis of OnabotulinumtoxinA (BOTOX®) for the Management of Urinary Incontinence in Adults with Neurogenic Detrusor Overactivity: A UK Perspective