Skip to main content

Advertisement

SpringerLink
Log in

Novel Oral Anticoagulants Versus Warfarin Therapy at Various Levels of Anticoagulation Control in Atrial Fibrillation—A Cost-Effectiveness Analysis

  • Original Research
  • Published:
Journal of General Internal Medicine Aims and scope Submit manuscript

ABSTRACT

BACKGROUND

The decision as to whether to use more expensive novel oral anticoagulants (NOACs) or invest resources for quality improvement of warfarin therapy requires input from both clinical and economic analyses.

OBJECTIVE

Cost-effectiveness of NOACs compared to warfarin therapy at various levels of patient-time in therapeutic range (TTR) in patients with atrial fibrillation was examined, from the healthcare provider’s perspective.

DESIGN, SUBJECTS AND INTERVENTION

A Markov model was used to compare life-long economic and treatment outcomes of warfarin and NOACs in a hypothetical cohort of 65-year-old atrial fibrillation patients with CHADS2 scores of 2 or above. Model inputs were derived from clinical trials published in the literature.

MAIN MEASURES

The outcome measure was incremental cost per quality-adjusted life-year (QALY) gained (ICER).

KEY RESULTS

Using United States Dollar (USD) 50,000 as the threshold of willingness-to-pay per QALY, NOACs therapy was cost-effective when TTR of warfarin therapy was 60 % or below, or monthly cost of warfarin management increased by two-fold or more to achieve 70 % TTR. Warfarin therapy was cost-effective when TTR of warfarin was 70 % with up to a 1.5-fold increment in monthly cost of care, or when TTR reached 75 % with monthly cost of warfarin care increased up to three-fold. At TTR 60 %, 70 % and 75 %, NOACs was cost-effective when monthly drug cost was < USD 200, < USD 122–185 and < USD 85–145, respectively. 10,000 Monte Carlo simulations showed NOACs to be cost-effective 83.6 %, 50.7 % and 32.7 % of the time at TTR of 60 %, 70 % and 75 %, respectively.

CONCLUSIONS

The acceptance of NOACs as cost-effective was highly dependent upon drug cost, anticoagulation control for warfarin, and anticoagulation service cost.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

REFERENCES

  1. Connolly SJ, Pogue J, Eikelboom J, 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;118:2029–37.

    Article  CAS  PubMed  Google Scholar 

  2. You JHS, Chan FWH, Wong RSM, Cheng G. Is INR, between 2.0 and 3.0 the optimal level for Chinese patients on warfarin therapy for moderate-intensity anticoagulation? Br J Clin Pharmacol. 2005;59:582–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Mantha S, Cabral K, Ansell J. New avenues for anticoagulation in atrial fibrillation. Clin Pharmacol Ther. 2013;93:68–77.

    Article  CAS  PubMed  Google Scholar 

  4. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.

    Article  CAS  PubMed  Google Scholar 

  5. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients atrial fibrillation. N Engl J Med. 2011;365:981–92.

    Article  CAS  PubMed  Google Scholar 

  6. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.

    Article  CAS  PubMed  Google Scholar 

  7. Lip GYH, Larsen TB, Skjoth F, Rasmussen LH. Indirect comparisons of new oral anticoagulant drugs for efficacy and safety when used for stroke prevention in atrial fibrillation. J Am Coll Cardiol. 2010;60:738–46.

    Article  Google Scholar 

  8. Rasmussen LH, Larsen TB, Graungaard T, Skjoth F, Lip GYH. Primary and secondary prevention with new oral anticoagulant drugs for stroke prevention in atrial fibrillation: indirect comparison analysis. BMJ. 2012;345:e7097. doi:10.1136/bmj.e7097.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Schneeweiss S, Gagne JJ, Patrick AR, Choudhry NK, Avorn J. Comparative efficacy and safety of new oral anticoagulants in patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2012;5:480–6.

    Article  PubMed Central  PubMed  Google Scholar 

  10. White HD, Cruber M, Feyzi J, et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control. Arch Intern Med. 2007;167:239–45.

    Article  CAS  PubMed  Google Scholar 

  11. Lee S, Anglade MW, Pham D, Pisacane R, Kluger J, Coleman GI. Cost-effectiveness of rivaroxaban compared to warfarin for stroke prevention in atrial fibrillation. Am J Cardiol. 2012;110:845–51.

    Article  CAS  PubMed  Google Scholar 

  12. Lee S, Mullin R, Blasawski J, Coleman GI. Cost-effectiveness of apixaban compared with warfarin for stroke prevention in atrial fibrillation. PLoS ONE. 2012;7:e47473. doi:10.1371/journal.pone.0047473.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. 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 fribrillation. Ann Intern Med. 2011;154:1–11.

    Article  PubMed  Google Scholar 

  14. Soresens SV, Kansal AR, Connolly S, Reng S, Linnehan J, Bradley-Kennedy C, et al. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillatioin: A Canadian payer perspective. Thromb Haemost. 2011;105:908–19.

    Article  Google Scholar 

  15. 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 economics analyses. BMJ. 2011;343:d6333. doi:10.1136/bmj.d6333.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation. 2011;123:2562–70.

    Article  PubMed  Google Scholar 

  17. Harrington AR, Armstrong EP, Nolan PE, Malone DC. Cost-effectiveness of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke. 2013;44:1676–81.

    Article  PubMed  Google Scholar 

  18. Kim YK, Nieuwlaat R, Connolly SJ, et al. Effect of a simple two-step warfarin dosing algorithm on anticoagulant control as measured by time in therapeutic range: a pilot study. J Thromb Haemost. 2010;8:101–6.

    Article  CAS  PubMed  Google Scholar 

  19. Samsa GP, Matchar DB. Relationship between test frequency and outcomes of anticoagulations: A literature review and commentary with implications for the design of randomized trials of patient self-management. J Thromb Thrombolysis. 2000;9:283–92.

    Article  CAS  PubMed  Google Scholar 

  20. Bloomfield HE, Krause A, Greer N, et al. Meta-analysis: effect of patient self-testing and self-management of long-term anticoagulation on major clinical outcomes. Ann Intern Med. 2011;154:472–82.

    Article  PubMed  Google Scholar 

  21. Heneghan C, Alonso-Coello P, Garcia-Alamino JM, Perera R, Meats E, Glasziou P. Self-monitoring of oral anticoagulation: a systematic review and meta-analysis. Lancet. 2006;367:404–11.

    Article  CAS  PubMed  Google Scholar 

  22. Chan FWH, Wong RSM, Lau WH, Chan TYK, Cheng G, You JHS. Management of Chinese patients on warfarin therapy in two models of anticoagulation service — A prospective randomized trial. Br J Clin Pharmaco l. 2006;62:601–9.

    Article  CAS  Google Scholar 

  23. Chiquette E, Amato MG, Bussey HI. Comparison of an anticoagulation clinic with usual medical care. Arch Intern Med. 1998;158:1641–7.

    Article  CAS  PubMed  Google Scholar 

  24. Witt DM, Delate T, Garcia DA, et al. Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med. 2012;172:1484–91.

    Article  CAS  PubMed  Google Scholar 

  25. Reynolds MW, Fahrbach K, Hauch O, et al. Warfarin anticoagulation and outcomes in patients with atrial fibrillation. A systematic review and metaanalysis. Chest. 2004;126:1938–45.

    Article  PubMed  Google Scholar 

  26. Dentali F, Riva N, Crowther M, Turpie AGG, Lip GYH, Ageno W. Efficacy and safety of the novel oral anticoagulants in atrial fibrillation. A systematic review and meta-analysis of the literature. Circulation. 2012;126:2381–91.

    Article  CAS  PubMed  Google Scholar 

  27. Stroke Prevention in Atrial Fibrillation Investigators. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet. 1996;348:633–8.

    Article  Google Scholar 

  28. Gage BF, van Walraven C, Pearce L, et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation. 2004;110:2287–92.

    Article  CAS  PubMed  Google Scholar 

  29. Hylek EM, Go AS, Chang Y, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med. 2003;349:1019–26.

    Article  CAS  PubMed  Google Scholar 

  30. van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA. 2002;288:2441–8.

    Article  PubMed  Google Scholar 

  31. Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370:493–503.

    Article  CAS  PubMed  Google Scholar 

  32. Fang MC, Go AS, Chang Y, et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med. 2007;120:700–5.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Hanger HC, Fletcher VJ, Wilkinson TJ, Brown AJ, Frampton CM, Sainsbury R. Effect of aspirin and warfarin on early survival after intracerebral haemorrhage. J Neurol. 2008;255:347–52.

    Article  CAS  PubMed  Google Scholar 

  34. Gage BF, Cardinalli AB, Owen DK. The effect of stroke and stroke prophylaxis with aspirin and warfarin on quality of life. Arch Intern Med. 1996;156:1829–36.

    Article  CAS  PubMed  Google Scholar 

  35. Thomson R, Parkin D, Ecclles M, Sudlow M, Robinson A. Decision analysis and guidelines for anticoagulant therapy to prevent stroke in patients with atrial fibrillation. Lancet. 2000;355:956–62.

    Article  CAS  PubMed  Google Scholar 

  36. Fryback DG, Dasbach EJ, Klein R, et al. The Beaver Dam Health Outcomes Study: initial catalog of health-state quality factors. Med Decis Making. 1993;13:89–102.

    Article  CAS  PubMed  Google Scholar 

  37. Sullivan PW, Ghushchyan V. Preference-based EQ-5D index scores for chronic conditions in the United States. Med Decis Making. 2006;26:410–20.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Drummond MF, Sculpher MJ, Torrance GW, et al. Methods for the economic evaluation of health care programmes. New York: Oxford University Press; 2005:189–90.

    Google Scholar 

  39. Centers for Medicare & Medicaid Services website (assessed on Nov 6, 2012): http://www.cms.gov/MedicareFeeforSvcPartsAB/03_MEDPAR.asp

  40. Agency for Healthcare Research and Policy. HCUPnet. http://hcupnet.ahrq.gov/. Accessed Nov 6, 2012.

  41. Mark DB, Knight JD, Cowper PA, Davidson-Ray L, Anstrom KJ. Long-term economic outcomes associated with intensive versus moderate lipid-lowering therapy in coronary artery disease: results from the Treating to New Targets (TNT) Trial. Am Heart J. 2008;156:698–705.

    Article  PubMed  Google Scholar 

  42. Tsevat J, Kuntz KM, Orav EJ, Weinstein MC, Sacks FM, Goldman L. Cost-effectiveness of pravastatin therapy for survivors of myocardial infarction with average cholesterol levels. Am Heart J. 2001;141:727–34.

    Article  CAS  PubMed  Google Scholar 

  43. Menzin J, Boulanger L, Hauch O, et al. Quality of anticoagulation control and costs of monitoring warfarin therapy among patients with atrial fibrillation in clinic settings: A multi-site managed-care study. Ann Pharmacother. 2005;39:446–51.

    Article  PubMed  Google Scholar 

  44. www.pharmacychecker.com. Accessed on 1 February 2013.

  45. Barnett MJ, Frank J, Wehring H, et al. Analysis of pharmacist-provided medication therapy management (MTM) services in community pharmacies over 7 years. J Manag Care Pharm. 2009;15:18–31.

    PubMed  Google Scholar 

  46. Weinstein MC, Siegel JE, Gold MR, Kamlet MS, Russel LB. Recommendations of the Panel on Cost-Effectiveness in Health and Medicine. JAMA. 1996;276:1253–8.

    Article  CAS  PubMed  Google Scholar 

  47. You JHS, Tsui KKN, Wong RSM, 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:e39640. doi:10.1371/journal.pone.0039640.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L, Randomized Evaluation of Long-Term Anticoagulation Therapy Investigators. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875–6.

    Article  CAS  PubMed  Google Scholar 

  49. ACTIVE Writing Group of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial Fibrillation Clopidogrel TrialWith Irbesartan for Prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367:1903–12.

    Article  Google Scholar 

  50. Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706–17.

    Article  CAS  PubMed  Google Scholar 

  51. Bernheim SM, Grady JN, Lin Z, 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;3:459–67.

    Article  PubMed Central  PubMed  Google Scholar 

  52. O’Brien CL, Gage BF. Costs and effectiveness of ximelagatran for stroke prophylaxis in chronic atrial fibrillation. JAMA. 2005;293:699–706.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was funded by General Research Fund from the Research Grants Council of the Hong Kong (Project no. CUHK477612).

Conflict of Interest

The authors declare that they do not have a conflict of interest.

Author information

Authors and Affiliations

  1. Centre for Pharmacoeconomics Research, School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China SAR

    Joyce H. S. You Pharm.D., BCPS

Authors
  1. Joyce H. S. You Pharm.D., BCPS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joyce H. S. You Pharm.D., BCPS.

Rights and permissions

Reprints and permissions

About this article

Cite this article

You, J.H.S. Novel Oral Anticoagulants Versus Warfarin Therapy at Various Levels of Anticoagulation Control in Atrial Fibrillation—A Cost-Effectiveness Analysis. J GEN INTERN MED 29, 438–446 (2014). https://doi.org/10.1007/s11606-013-2639-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11606-013-2639-2

KEY WORDS

Search

Navigation