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Cost–Effectiveness of Different Strategies for Stroke Prevention in Patients with Atrial Fibrillation in a Health Resource-Limited Setting

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Abstract

Purpose

To compare the lifetime cost and effectiveness of five alternative chronic atrial fibrillation (AF) management strategies: rivaroxaban, warfarin, aspirin plus clopidogrel, aspirin and no prevention.

Methods

An individual-level state-transition model was developed to track the lifetime disease course associated with AF. The clinical and utility data were derived from published studies. The cost data were estimated based on local charges and current Chinese practices. Sensitivity analyses were used to explore the impact of uncertainty on the results.

Results

For base-case patients with a CHADS2 score of 3, the cost per additional quality-adjusted life-years (QALYs) gained for rivaroxaban compared with no prevention, aspirin, aspirin plus clopidogrel and warfarin was $116,884, $153,944, $155,979 and $216,273, respectively. CHADS2 score had a substantial impact on the model outcomes for different prevention strategies. The time distribution of warfarin international normalised ratio (INR), stroke and intracranial haemorrhage (ICH) risks, cost of rivaroxaban and utility of warfarin therapy had substantial impacts on the results. Based on a willingness-to-pay threshold of $16,350/QALY, no prevention strategy was the preferred therapy for a patient with a low risk for stroke and a high risk for ICH; aspirin was preferred for patients with a moderate risk for stroke and ICH; and warfarin was preferred for patients with a high risk for stroke and a low risk of ICH.

Conclusion

In the context of limited health resources, rivaroxaban is unlikely to be cost-effective, although it provided more health benefits comparing with other strategies. Additionally, warfarin with good INR control might be more suitable for AF patients in developing regions.

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Abbreviations

ICH:

intracranial hemorrhage

INR:

international normalized ratio

RIND:

reversible ischemic neurologic event

TIA:

transient ischemic attack

MI:

myocardial infarction

References

  1. Magnani JW, Rienstra M, Lin H, Sinner MF, Lubitz SA, McManus DD, et al. Atrial Fibrillation Current Knowledge and Future Directions in Epidemiology and Genomics. Circulation. 2011;124(18):1982–U170. doi:10.1161/circulationaha.111.039677.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110(9):1042–6. doi:10.1161/01.CIR.0000140263.20897.42.

    Article  PubMed  Google Scholar 

  3. Heeringa J, van der Kuip DA, Hofman A, Kors JA, van Herpen G, Stricker BH, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006;27(8):949–53. doi:10.1093/eurheartj/ehi825.

    Article  PubMed  Google Scholar 

  4. Hu D, Sun Y. Epidemiology, risk factors for stroke, and management of atrial fibrillation in China. J Am Coll Cardiol. 2008;52(10):865–8. doi:10.1016/j.jacc.2008.05.042.

    Article  PubMed  Google Scholar 

  5. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998;82(8A):2N–9N.

    Article  CAS  PubMed  Google Scholar 

  6. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation. 2006;114(2):119–25. doi:10.1161/CIRCULATIONAHA.105.595140.

    Article  PubMed  Google Scholar 

  7. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. Jama. 2001;285(18):2370–5.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Wolf PA, Dawber TR, Thomas Jr HE, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology. 1978;28(10):973–7.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  PubMed  Google Scholar 

  11. Singer DE, Albers GW, Dalen JE, Go AS, Halperin JL, Manning WJ. Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):429S–56S. doi:10.1378/chest.126.3_suppl.429S.

    Article  CAS  PubMed  Google Scholar 

  12. Matchar DB, Jacobson A, Dolor R, Edson R, Uyeda L, Phibbs CS, et al. Effect of home testing of international normalized ratio on clinical events. N Engl J Med. 2010;363(17):1608–20. doi:10.1056/NEJMoa1002617.

    Article  CAS  PubMed  Google Scholar 

  13. Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J. 2007;7(2):99–111. doi:10.1038/sj.tpj.6500417.

    Article  CAS  PubMed  Google Scholar 

  14. Steffel J, Braunwald E. Novel oral anticoagulants: focus on stroke prevention and treatment of venous thrombo-embolism. Eur Heart J. 2011;32(16):1968–76. doi:10.1093/eurheartj/ehr052. 76a.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. Goff T, Kontakis G, Giannoudis PV. Safety and efficacy of rivaroxaban for thromboprophylaxis following lower limb surgery: an update. Expert Opin Drug Saf. 2011;10(5):687–96. doi:10.1517/14740338.2011.558500.

    Article  CAS  PubMed  Google Scholar 

  17. Wasserlauf G, Grandi SM, Filion KB, Eisenberg MJ. Meta-analysis of rivaroxaban and bleeding risk. Am J Cardiol. 2013;112(3):454–60. doi:10.1016/j.amjcard.2013.03.054.

    Article  CAS  PubMed  Google Scholar 

  18. You JH, Tsui KK, Wong RS, Cheng G. Cost-effectiveness of dabigatran versus genotype-guided management of warfarin therapy for stroke prevention in patients with atrial fibrillation. PLoS One. 2012;7(6):e39640. doi:10.1371/journal.pone.0039640.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Davidson T, Husberg M, Janzon M, Oldgren J, Levin LA. Cost-effectiveness of dabigatran compared with warfarin for patients with atrial fibrillation in Sweden. Eur Heart J. 2012. doi:10.1093/eurheartj/ehs157.

    Google Scholar 

  20. Kansal AR, Sorensen SV, Gani R, Robinson P, Pan F, Plumb JM, et al. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation. Heart. 2012;98(7):573–8. doi:10.1136/heartjnl-2011-300646.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Kamel H, Johnston SC, Easton JD, Kim AS. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack. Stroke; a journal of cerebral circulation. 2012;43(3):881–3. doi:10.1161/STROKEAHA.111.641027.

    Article  PubMed  Google Scholar 

  22. Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation. 2011;123(22):2562–70. doi:10.1161/CIRCULATIONAHA.110.985655.

    Article  PubMed  Google Scholar 

  23. Sorensen SV, Kansal AR, Connolly S, Peng S, Linnehan J, Bradley-Kennedy C, et al. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: a Canadian payer perspective. Thromb Haemost. 2011;105(5):908–19. doi:10.1160/TH11-02-0089.

    Article  CAS  PubMed  Google Scholar 

  24. 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:10.1059/0003-4819-154-1-201101040-00289.

    Article  PubMed  Google Scholar 

  25. Lee S, Anglade MW, Pham D, Pisacane R, Kluger J, Coleman CI. Cost-effectiveness of rivaroxaban compared to warfarin for stroke prevention in atrial fibrillation. Am J Cardiol. 2012;110(6):845–51. doi:10.1016/j.amjcard.2012.05.011.

    Article  CAS  PubMed  Google Scholar 

  26. Lee S, Mullin R, Blazawski J, Coleman CI. Cost-effectiveness of apixaban compared with warfarin for stroke prevention in atrial fibrillation. PLoS One. 2012;7(10):e47473. doi:10.1371/journal.pone.0047473.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Kamel H, Easton JD, Johnston SC, Kim AS. Cost-effectiveness of apixaban vs warfarin for secondary stroke prevention in atrial fibrillation. Neurology. 2012;79(14):1428–34. doi:10.1212/WNL.0b013e31826d5fe8.

    Article  PubMed  Google Scholar 

  28. 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(4):498–506. doi:10.1016/j.jval.2013.01.009.

    Article  PubMed  Google Scholar 

  29. Harrington AR, Armstrong EP, Nolan Jr PE, Malone DC. Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke. 2013;44(6):1676–81. doi:10.1161/STROKEAHA.111.000402.

    Article  PubMed  Google Scholar 

  30. 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. doi:10.1371/journal.pone.0062183.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Siebert U, Alagoz O, Bayoumi AM, Jahn B, Owens DK, Cohen DJ, et al. State-transition modeling: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force–3. Value Health. 2012;15(6):812–20. doi:10.1016/j.jval.2012.06.014.

    Article  PubMed  Google Scholar 

  32. Barton P, Bryan S, Robinson S. Modelling in the economic evaluation of health care: selecting the appropriate approach. J Health Serv Res Policy. 2004;9(2):110–8. doi:10.1258/135581904322987535.

    Article  PubMed  Google Scholar 

  33. Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367(9526):1903–12. doi:10.1016/S0140-6736(06)68845-4.

    Article  CAS  PubMed  Google Scholar 

  34. Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet. 1989;1(8631):175–9.

    Article  CAS  PubMed  Google Scholar 

  35. Bhatt DL, Fox KAA, Hacke W, Berger PB, Black HR, Boden WE, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. New England Journal of Medicine. 2006;354(16):1706–17. doi:10.1056/NEJMoa060989.

    Article  CAS  PubMed  Google Scholar 

  36. Gullov AL, Koefoed BG, Petersen P, Pedersen TS, Andersen ED, Godtfredsen J, et al. Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. Arch Intern Med. 1998;158(14):1513–21.

    Article  CAS  PubMed  Google Scholar 

  37. Taylor FC, Cohen H, Ebrahim S. Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation. Bmj. 2001;322(7282):321–6.

    Article  CAS  PubMed  Google Scholar 

  38. Zhou Z, Hu D. An epidemiological study on the prevalence of atrial fibrillation in the Chinese population of mainland China. J Epidemiol. 2008;18(5):209–16.

    Article  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. Aguilar MI, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev. 2005(3):CD001927. doi:10.1002/14651858.CD001927.pub2.

  41. Lip GY, Lim HS. Atrial fibrillation and stroke prevention. Lancet Neurol. 2007;6(11):981–93. doi:10.1016/S1474-4422(07)70264-8.

    Article  CAS  PubMed  Google Scholar 

  42. Connolly SJ, Laupacis A, Gent M, Roberts RS, Cairns JA, Joyner C. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol. 1991;18(2):349–55.

    Article  CAS  PubMed  Google Scholar 

  43. Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, Chrolavicius S, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009;360(20):2066–78. doi:10.1056/NEJMoa0901301.

    Article  PubMed  Google Scholar 

  44. 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.

    Article  CAS  PubMed  Google Scholar 

  45. 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(4):309–15. doi:10.1016/j.jacc.2007.01.098.

    Article  PubMed  Google Scholar 

  46. Ariesen MJ, Claus SP, Rinkel GJ, Algra A. Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke; a journal of cerebral circulation. 2003;34(8):2060–5. doi:10.1161/01.STR.0000080678.09344.8D.

    Article  CAS  PubMed  Google Scholar 

  47. 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.

    Article  CAS  PubMed  Google Scholar 

  48. Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation. 1991;84(2):527–39.

    Article  Google Scholar 

  49. Whyte S, Walsh C, Chilcott J. Bayesian calibration of a natural history model with application to a population model for colorectal cancer. Med Decis Making. 2011;31(4):625–41. doi:10.1177/0272989X10384738.

    Article  PubMed  Google Scholar 

  50. Agarwal S, Hachamovitch R, Menon V. Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Arch Intern Med. 2012;172(8):623–31. doi:10.1001/archinternmed.2012.121. discussion 31–3.

    Article  PubMed  Google Scholar 

  51. Bernheim SM, Grady JN, Lin Z, Wang Y, Savage SV, Bhat KR, et al. National patterns of risk-standardized mortality and readmission for acute myocardial infarction and heart failure. Update on publicly reported outcomes measures based on the 2010 release. Circ Cardiovasc Qual Outcomes. 2010;3(5):459–67. doi:10.1161/CIRCOUTCOMES.110.957613.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Poli D, Testa S, Antonucci E, Grifoni E, Paoletti O, Lip GY. Bleeding and stroke risk in a real-world prospective primary prevention cohort of patients with atrial fibrillation. Chest. 2011;140(4):918–24. doi:10.1378/chest.10-3024.

    Article  PubMed  Google Scholar 

  53. Ce Z. Anticoagulation Efficacy of Warfarin: Analysis of 95 Cases. China Pharmacy. 2009;20(32):2527–9. doi:1001-0408(2009)20:32<2527:9lhzhf>2.0.tx;2-y.

    Google Scholar 

  54. Life tables for WHO Member States. http://www.who.int/healthinfo/statistics/mortality_life_tables/en/. Accessed 2012 September 18.

  55. Barton P, Jobanputra P, Wilson J, Bryan S, Burls A. The use of modelling to evaluate new drugs for patients with a chronic condition: the case of antibodies against tumour necrosis factor in rheumatoid arthritis - Introduction. Health Technol Assess. 2004;8(11):1.

    Google Scholar 

  56. O'Brien CL, Gage BF. Costs and effectiveness of ximelagatran for stroke prophylaxis in chronic atrial fibrillation. Jama. 2005;293(6):699–706. doi:10.1001/jama.293.6.699.

    Article  PubMed  Google Scholar 

  57. Sui-feng L, Zai-jin J, Min O. A warfarin-dosing algorithm on atrial fibrillation in elderly patients. Chinese Journal Of Geriatrics. 2008;27(4):262–5.

    Google Scholar 

  58. Eichler HG, Kong SX, Gerth WC, Mavros P, Jonsson B. Use of cost-effectiveness analysis in health-care resource allocation decision-making: how are cost-effectiveness thresholds expected to emerge? Value Health. 2004;7(5):518–28. doi:10.1111/j.1524-4733.2004.75003.x.

    Article  PubMed  Google Scholar 

  59. Murray CJ, Evans DB, Acharya A, Baltussen RM. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ. 2000;9(3):235–51.

    Article  CAS  PubMed  Google Scholar 

  60. Zhao FL, Yue M, Yang H, Wang T, Wu JH, Li SC. Willingness to pay per quality-adjusted life year: is one threshold enough for decision-making?: results from a study in patients with chronic prostatitis. Med Care. 2011;49(3):267–72. doi:10.1097/MLR.0b013e31820192cd.

    Article  PubMed  Google Scholar 

  61. Baker WL, Cios DA, Sander SD, Coleman CI. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm. 2009;15(3):244–52.

    PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant from the Program of Shanghai Chief Science (35508XD14026).

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Clinical Outcomes and Economics Group, Department of pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Bin Wu & Xiaoyan Liu

  2. Center for ADR Monitoring of Linyi, Linyi, China

    Li Kun

  3. Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Ben He

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  1. Bin Wu
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  2. Li Kun
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  3. Xiaoyan Liu
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Wu, B., Kun, L., Liu, X. et al. Cost–Effectiveness of Different Strategies for Stroke Prevention in Patients with Atrial Fibrillation in a Health Resource-Limited Setting. Cardiovasc Drugs Ther 28, 87–98 (2014). https://doi.org/10.1007/s10557-013-6490-9

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