Journal of General Internal Medicine

, Volume 29, Issue 3, pp 438–446 | Cite as

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

Original Research



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.


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.


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.


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


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.


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


novel oral anticoagulants warfarin atrial fibrillation cost-effectiveness 


  1. 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.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Mantha S, Cabral K, Ansell J. New avenues for anticoagulation in atrial fibrillation. Clin Pharmacol Ther. 2013;93:68–77.PubMedCrossRefGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients atrial fibrillation. N Engl J Med. 2011;365:981–92.PubMedCrossRefGoogle Scholar
  6. 6.
    Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.PubMedCrossRefGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation. 2011;123:2562–70.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 23.
    Chiquette E, Amato MG, Bussey HI. Comparison of an anticoagulation clinic with usual medical care. Arch Intern Med. 1998;158:1641–7.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.CrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 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. 39.
    Centers for Medicare & Medicaid Services website (assessed on Nov 6, 2012):
  40. 40.
    Agency for Healthcare Research and Policy. HCUPnet. Accessed Nov 6, 2012.
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 44. Accessed on 1 February 2013.
  45. 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.PubMedGoogle Scholar
  46. 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.PubMedCrossRefGoogle Scholar
  47. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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.CrossRefGoogle Scholar
  50. 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.PubMedCrossRefGoogle Scholar
  51. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    O’Brien CL, Gage BF. Costs and effectiveness of ximelagatran for stroke prophylaxis in chronic atrial fibrillation. JAMA. 2005;293:699–706.PubMedCrossRefGoogle Scholar

Copyright information

© Society of General Internal Medicine 2013

Authors and Affiliations

  1. 1.Centre for Pharmacoeconomics Research, School of Pharmacy, Faculty of MedicineThe Chinese University of Hong KongShatinChina SAR

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