Advertisement

PharmacoEconomics

, Volume 37, Issue 2, pp 279–289 | Cite as

Cost-Effectiveness Analysis of Direct-Acting Oral Anticoagulants for Stroke Prevention in Thai Patients with Non-Valvular Atrial Fibrillation and a High Risk of Bleeding

  • Thananan Rattanachotphanit
  • Chulaporn LimwattananonEmail author
  • Onanong Waleekhachonloet
  • Phumtham Limwattananon
  • Kittisak Sawanyawisuth
Original Research Article

Abstract

Objective

The objective of this study was to assess the cost effectiveness of direct-acting oral anticoagulants for stroke prevention in Thai patients with non-valvular atrial fibrillation and a HAS-BLED score of 3.

Methods

Total costs (US$) in 2017 and quality-adjusted life-years were estimated over 20 years using a Markov model. A base-case analysis was conducted under a societal perspective, which included direct healthcare, non-healthcare and indirect costs in Thailand. Clinical events for warfarin and utilities were obtained from Thai patients whenever possible. The efficacy of direct-acting oral anticoagulants was derived from trial-based East Asian subgroups and adjusted for time in the target international normalized ratio range of warfarin.

Results

In the base case, use of apixaban instead of warfarin incurred an additional cost of US$20,763 per quality-adjusted life-year gained. Substituting apixaban with rivaroxaban and rivaroxaban with high-dose edoxaban would incur an additional cost per quality-adjusted life-year by US$507 and US$434, respectively. Compared with warfarin, high-dose edoxaban had the lowest incremental cost-effectiveness ratio of US$9704/quality-adjusted life-year, followed by high-dose dabigatran (incremental cost-effectiveness ratio US$11,155/quality-adjusted life-year). The incremental cost-effectiveness ratios based on a payer perspective were similar. The incremental cost-effectiveness ratio was below Thailand’s cost-effectiveness threshold when high-dose dabigatran and edoxaban prices were reduced by 50%. Changes in key parameters had a minimal impact on incremental cost-effectiveness ratios.

Conclusions

For both societal and payer perspectives, high-dose edoxaban with a price below the country cost-effectiveness threshold should be the first anticoagulant option for Thai patients with non-valvular atrial fibrillation and a high risk of bleeding.

Notes

Acknowledgements

The authors thank Dr. Cynthia R. Gross and Dr. Jeffrey Roy Johns for providing editing assistance. The authors also thank four reviewers for valuable comments.

Author Contributions

TR provided the study concept and design, and contributed to the analysis and interpretation of the data and drafting of the paper. CL provided the study concept and design, contributed to the analysis and interpretation of the data and drafting of the paper, and critically revised the paper for intellectual content. OW contributed to the analysis and interpretation of the data. PL and KS critically revised the paper for intellectual content. All authors were involved in the final approval of the version to be published and agree to be accountable for all aspects of the work.

Funding

This study was funded by the Faculty of Pharmaceutical Sciences, Khon Kaen University.

Compliance with Ethical Standards

Conflicts of interest

Thananan Rattanachotphanit, Chulaporn Limwattananon, Onanong Waleekhachonloet, Phumtham Limwattananon, and Kittisak Sawanyawisuth have no conflicts of interest that are directly relevant to the contents of this study.

Data Availability

All data generated or analyzed during this study are included in this published article and its Electronic Supplementary Material.

Supplementary material

40273_2018_741_MOESM1_ESM.docx (262 kb)
Supplementary material 1 (DOCX 261 kb)

References

  1. 1.
    Watson T, Shantsila E, Lip GY. Mechanisms of thrombogenesis in atrial fibrillation: Virchow’s triad revisited. Lancet. 2009;373:155–66.CrossRefGoogle Scholar
  2. 2.
    European Society of Cardiology. Atrial fibrillation 2016 (management of): ESC clinical practice guidelines. Available from: https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Atrial-Fibrillation-Management. Accessed 2 Dec 2016.
  3. 3.
    Lip GY, Lane DA. Stroke prevention in atrial fibrillation: a systematic review. JAMA. 2015;313:1950–62.CrossRefGoogle Scholar
  4. 4.
    López-López JA, Sterne JAC, Thom HHZ, Higgins JPT, Hingorani AD, Okoli GN, et al. Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ. 2017;359:j5058.  https://doi.org/10.1136/bmj.j5058.CrossRefGoogle Scholar
  5. 5.
    Shah A, Shewale A, Hayes CJ, Martin BC. Cost-effectiveness of oral anticoagulants for ischemic stroke prophylaxis among nonvalvular atrial fibrillation patients. Stroke. 2016;47:1555–61.CrossRefGoogle Scholar
  6. 6.
    Wisløff T, Hagen G, Klemp M. Economic evaluation of warfarin, dabigatran, rivaroxaban, and apixaban for stroke prevention in atrial fibrillation. Pharmacoeconomics. 2014;32:601–12.CrossRefGoogle Scholar
  7. 7.
    Lanitis T, Cotté 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;17:587–98.CrossRefGoogle Scholar
  8. 8.
    Harrington AR, Armstrong EP, Nolan PE Jr, Malone DC. Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke. 2013;44:1676–81.CrossRefGoogle Scholar
  9. 9.
    Canestaro WJ, Patrick AR, Avorn J, Ito K, Matlin OS, Brennan TA, et al. Cost-effectiveness of oral anticoagulants for treatment of atrial fibrillation. Circ Cardiovasc Qual Outcome. 2013;6:724–31.CrossRefGoogle Scholar
  10. 10.
    Zheng Y, Sorensen SV, Gonschior AK, Noack H, Heinrich-Nols J, Sunderland T, et al. Comparison of the cost-effectiveness of new oral anticoagulants for the prevention of stroke and systemic embolism in atrial fibrillation in a UK setting. Clin Ther. 2014;36:2015–28.CrossRefGoogle Scholar
  11. 11.
    Rognoni C, Marchetti M, Quaglini S, Liberato NL. Apixaban, dabigatran, and rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis. Clin Drug Investig. 2014;34:9–17.CrossRefGoogle Scholar
  12. 12.
    Coyle D, Coyle K, Cameron C, Lee K, Kelly S, Steiner S, et al. Cost-effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with atrial fibrillation. Value Health. 2013;16:498–506.CrossRefGoogle Scholar
  13. 13.
    Hernandez I, Smith KJ, Zhang Y. Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation at high risk of bleeding and normal kidney function. Thromb Res. 2017;150:123–30.CrossRefGoogle Scholar
  14. 14.
    Hospodar AR, Smith KJ, Zhang Y, Hernandez I. Comparing the cost effectiveness of non-vitamin k antagonist oral anticoagulants with well-managed warfarin for stroke prevention in atrial fibrillation patients at high risk of bleeding. Am J Cardiovasc Drugs. 2018 May 9.  https://doi.org/10.1007/s40256-018-0279-y. [Epub ahead of print].
  15. 15.
    Jarungsuccess S, Taerakun S. Cost-utility analysis of oral anticoagulants for nonvalvular atrial fibrillation patients at the police general hospital, Bangkok, Thailand. Clin Ther. 2014;36:1389–94.CrossRefGoogle Scholar
  16. 16.
    Tse HF, Wang YJ, Ahmed Ai-Abdullah M, Pizarro-Borromeo AB, Chiang CE, Krittayaphong R, et al. Stroke prevention in atrial fibrillation: an Asian stroke perspective. Heart Rhythm. 2013;10:1082–8.CrossRefGoogle Scholar
  17. 17.
    Chau PH, Woo J, Goggins WB, Tse YK, Chan KC, Lo SV, Ho SC. Trends in stroke incidence in Hong Kong differ by stroke subtype. Cerebrovasc Dis. 2011;31:138–46.CrossRefGoogle Scholar
  18. 18.
    Shen AY, Yao JF, Brar SS, Jorgensen MB, Chen W. Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol. 2007;50:309–15.CrossRefGoogle Scholar
  19. 19.
    Chiang CE, Wang KL, Lip GYH. Stroke prevention in atrial fibrillation: an Asian perspective. Thromb Haemost. 2014;111:789–97.CrossRefGoogle Scholar
  20. 20.
    Chaikledkaew U. Guidelines for health technology assessment in Thailand. 2nd ed. Nonthaburi: Wacharinprint; 2013.Google Scholar
  21. 21.
    Sorensen SV, Dewilde S, Singer DE, Goldhaber SZ, Monz BU, Plumb JM. Cost-effectiveness of warfarin: trial versus “real-world” stroke prevention in atrial fibrillation. Am Heart J. 2009;157:1064–73.CrossRefGoogle Scholar
  22. 22.
    Methavigul K, Boonyapisit W. Optimal INR level in Thai atrial fibrillation patients who were receiving warfarin for stroke prevention in Thailand. J Med Assoc Thail. 2014;97:1274–80.Google Scholar
  23. 23.
    Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138:1093–100.CrossRefGoogle Scholar
  24. 24.
    Kansal AR, Sharma M, Bradley-Kennedy C, Clemens A, Monz BU, Peng S, et al. Dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in atrial fibrillation in Canada: comparative efficacy and cost-effectiveness. Thromb Haemost. 2012;108:672–82.CrossRefGoogle Scholar
  25. 25.
    Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007;69:546–54.CrossRefGoogle Scholar
  26. 26.
    Expert Panel on Detection Evaluation Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97.Google Scholar
  27. 27.
    Ariesen M, Claus S, Rinkel G, Algra A. Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke. 2003;34:2060–5.CrossRefGoogle Scholar
  28. 28.
    Phrommintikul A, Detnuntarat P, Prasertwitayakij N, Wancharoen W. Prevalence of atrial fibrillation in Thai elderly. J Geriatr Cardiol. 2016;13:270–3.Google Scholar
  29. 29.
    Krittayaphong R, Winijkul A, Methavigul K, Wongtheptien W, Wongvipaporn C, Wisaratapong T, et al. Risk profiles and pattern of antithrombotic use in patients with non-valvular atrial fibrillation in Thailand: a multicenter study. BMC Cardiovasc Disord. 2018;18:174.  https://doi.org/10.1186/s12872-018-0911-4.CrossRefGoogle Scholar
  30. 30.
    Goto S, Zhu J, Liu L, Oh BH, Wojdyla DM, Aylward P, et al. Efficacy and safety of apixaban compared with warfarin for stroke prevention in patients with atrial fibrillation from East Asia: a subanalysis of the apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation (ARISTOTLE) trial. Am Heart J. 2014;168:303–9.CrossRefGoogle Scholar
  31. 31.
    Hori M, Connolly SJ, Zhu J, Liu LS, Lau C, Pais P, et al. Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and Non-Asians with atrial fibrillation. Stroke. 2013;44:1891–6.CrossRefGoogle Scholar
  32. 32.
    Yamashita T, Koretsune Y, Yang Y, Chen S, Chung N, Shimada YJ et al. Edoxaban vs. warfarin in East Asian patients with atrial fibrillation: an ENGAGE AF-TIMI 48 subanalysis. Circ J. 2016;80:860–9.Google Scholar
  33. 33.
    Wong KS, Hu DY, Oomman A, Tan RS, Patel MR, Singer DE, et al. Rivaroxaban for stroke prevention in East Asian patients from the ROCKET-AF trial. Stroke. 2014;45:1739–47.CrossRefGoogle Scholar
  34. 34.
    Roskell NS, Samuel M, Noack H, Monz BU. Major bleeding in patients with atrial fibrillation receiving vitamin K antagonists: a systematic review of randomized and observational studies. Europace. 2013;15:787–97.CrossRefGoogle Scholar
  35. 35.
    World Health Organization. Global health observatory data repository: life tables by country Thailand. http://apps.who.int/gho/data/?theme=main&vid=61640. Accessed 2 Dec 2016.
  36. 36.
    Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98:946–52.CrossRefGoogle Scholar
  37. 37.
    Odutayo A, Wong CX, Hsiao AJ, Hopewell S, Altman DG, Emdin CA. Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis. BMJ. 2016;354:i4482.CrossRefGoogle Scholar
  38. 38.
    Miller JD, Ye X, Lenhart GM, Farr AM, Tran OV, Kwong WJ, et al. Cost-effectiveness of edoxaban versus rivaroxaban for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in the US. Clin Outcome Res. 2016;8:215–26.CrossRefGoogle Scholar
  39. 39.
    Dorian P, Kongnakorn T, Phatak H, Rublee DA, Kuznik A, Lanitis T. Cost-effectiveness of apixaban vs current standard of care for stroke prevention in patients with atrial fibrillation. Eur Heart J. 2014;35:1897–906.CrossRefGoogle Scholar
  40. 40.
    Lip GY, Kongnakorn T, Phatak H, Kuznik A, Lanitis T, Liu LZ, et al. Cost-effectiveness of apixaban versus other new oral anticoagulants for stroke prevention in atrial fibrillation. Clin Ther. 2014;36(192–210):e20.Google Scholar
  41. 41.
    Saokaew S, Sapoo U, Nathisuwan S, et al. Anticoagulation control of pharmacist-managed collaborative care versus usual care in Thailand. Int J Clin Pharmacol. 2012;34:105–12.CrossRefGoogle Scholar
  42. 42.
    Riewpaiboon A. Standard cost lists for health technology assessment. 2010. http://www.hitap.net/costingmenu/. Accessed 9 Dec 2012.
  43. 43.
    Riewpaiboon A, Riewpaiboon W, Ponsoongnern K, Van den Berg B. Economic valuation of informal care in Asia: a case study of care for disabled stroke survivors in Thailand. Soc Sci Med. 2009;69:648–53.CrossRefGoogle Scholar
  44. 44.
    Briggs AH, Claxton K, Schulpher MJ. Decision modeling for health economic evaluation. Oxford: Oxford University Press; 2006.Google Scholar
  45. 45.
    Yoon SS, Chang H, Kwon YD. Itemized hospital charges for acute cerebral infarction patients influenced by severity in an academic medical center in Korea. J Clin Neurol. 2012;8:58–64.  https://doi.org/10.3988/jcn.2012.8.1.58.CrossRefGoogle Scholar
  46. 46.
    Li X, Tse VC, Lau WC, Cheung BM, Lip GY, Wong IC. Cost-effectiveness of apixaban versus warfarin in chinese patients with non-valvular atrial fibrillation: a real-life and modelling analyses. PLoS One. 2016;11(6):e0157129.  https://doi.org/10.1371/journal.pone.0157129.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Clinical Pharmacy, Faculty of PharmacyMahasarakham UniversityMahasarakhamThailand
  2. 2.Division of Clinical Pharmacy, Faculty of Pharmaceutical SciencesKhon Kaen UniversityKhon KaenThailand
  3. 3.Neurosurgery Residency Program, Department of Surgery, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand
  4. 4.Department of Internal Medicine, Faculty of MedicineKhon Kaen UniversityKhon KaenThailand

Personalised recommendations