Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Cost-effectiveness of pharmacogenetic-guided dosing of warfarin in the United Kingdom and Sweden


We aimed to assess the cost-effectiveness of pharmacogenetic-guided dosing of warfarin in patients with atrial fibrillation (AF) in the United Kingdom and Sweden. Data from EU-PACT, a randomized controlled trial in newly diagnosed AF patients, were used to model the incremental costs per quality-adjusted life-year (QALY) gained by pharmacogenetic-guided warfarin dosing versus standard treatment over a lifetime horizon. Incremental lifetime costs were £26 and 382 Swedish kronor (SEK) and incremental QALYs were 0.0039 and 0.0015 in the United Kingdom and Sweden, respectively. The corresponding incremental cost-effectiveness ratios (ICERs) were £6 702 and 253 848 SEK per QALY gained. The ICER was below the willingness-to-pay threshold of £20 000 per QALY gained in 93% of the simulations in the United Kingdom and below 500 000 SEK in 67% of the simulations in Sweden. Our data suggest that pharmacogenetic-guided dosing of warfarin is a cost-effective strategy to improve outcomes of patients with AF treated with warfarin in the United Kingdom and in Sweden.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others


  1. Lip GY, Lane DA . Stroke prevention in atrial fibrillation: a systematic review. JAMA 2015; 313: 1950–1962.

    Article  PubMed  Google Scholar 

  2. Wysowski DK, Nourjah P, Swartz L . Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arc int med 2007; 167: 1414–1419.

    Article  Google Scholar 

  3. Schalekamp T, de Boer A . Pharmacogenetics of oral anticoagulant therapy. Curr pharm des 2010; 16: 187–203.

    Article  CAS  PubMed  Google Scholar 

  4. Wadelius M, Chen LY, Lindh JD, Eriksson N, Ghori MJ, Bumpstead S et al. The largest prospective warfarin-treated cohort supports genetic forecasting. Blood 2009; 113: 784–792.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. International Warfarin Pharmacogenetics C International Warfarin Pharmacogenetics C Klein TE International Warfarin Pharmacogenetics C Altman RB International Warfarin Pharmacogenetics C Eriksson N International Warfarin Pharmacogenetics C Gage BF International Warfarin Pharmacogenetics C Kimmel SE et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med 2009; 360: 753–764.

    Article  Google Scholar 

  6. Lenzini P, Wadelius M, Kimmel S, Anderson JL, Jorgensen AL, Pirmohamed M et al. Integration of genetic, clinical, and INR data to refine warfarin dosing. Clin Pharmacol Ther 2010; 87: 572–578.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Verhoef TI, Ragia G, de Boer A, Barallon R, Kolovou G, Kolovou V et al. A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon. N Engl j med 2013; 369: 2304–2312.

    Article  CAS  PubMed  Google Scholar 

  8. 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: 2294–2303.

    Article  CAS  PubMed  Google Scholar 

  9. 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: 2283–2293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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 (British Cardiac Society) 2005; 91: 472–477.

    Article  CAS  Google Scholar 

  11. 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: 2309–2316.

    Article  CAS  PubMed  Google Scholar 

  12. Avery PJ, Jorgensen A, Hamberg AK, Wadelius M, Pirmohamed M, Kamali F et al. A proposal for an individualized pharmacogenetics-based warfarin initiation dose regimen for patients commencing anticoagulation therapy. Clin Pharmacol Ther 2011; 90: 701–706.

    Article  CAS  PubMed  Google Scholar 

  13. 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: 1405–1417.

    Article  CAS  PubMed  Google Scholar 

  14. Meckley LM, Gudgeon JM, Anderson JL, Williams MS, Veenstra DL . A policy model to evaluate the benefits, risks and costs of warfarin pharmacogenomic testing. PharmacoEconomics 2010; 28: 61–74.

    Article  PubMed  Google Scholar 

  15. Verhoef TI, Redekop WK, Veenstra DL, Thariani R, Beltman PA, van Schie RM et al. Cost-effectiveness of pharmacogenetic-guided dosing of phenprocoumon in atrial fibrillation. Pharmacogenomics 2013; 14: 869–883.

    Article  CAS  PubMed  Google Scholar 

  16. Verhoef TI, Redekop WK, de Boer A, Maitland-van der Zee AH . Economic evaluation of a pharmacogenetic dosing algorithm for coumarin anticoagulants in the Netherlands. Pharmacogenomics 2015; 16: 101–114.

    Article  CAS  PubMed  Google Scholar 

  17. Shah SV, Gage BF . Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation. Circulation 2011; 123: 2562–2570.

    Article  PubMed  Google Scholar 

  18. O'Brien CL, Gage BF . Costs and effectiveness of ximelagatran for stroke prophylaxis in chronic atrial fibrillation. JAMA: j Am Med Assoc 2005; 293: 699–706.

    Article  CAS  Google Scholar 

  19. Federation of Dutch Anticoagulant clinics. Samenvatting medische jaarverslagen 2012.

  20. Fang MC, Go AS, Chang Y, Hylek EM, Henault LE, Jensvold NG et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am j med 2007; 120: 700–705.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Connolly SJ, Eikelboom J, Joyner C, Diener HC, Hart R, Golitsyn S et al. Apixaban in patients with atrial fibrillation. N Engl j med 2011; 364: 806–817.

    Article  CAS  PubMed  Google Scholar 

  22. 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: 857–867.

    Article  PubMed  Google Scholar 

  23. Office of National Statistics, life tables.

  24. World Health Organization, Global Health Observatory Data Repository.

  25. Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E . A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236–239.

    Article  CAS  PubMed  Google Scholar 

  26. 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: 975–983.

    Article  CAS  PubMed  Google Scholar 

  27. Oake N, Jennings A, Forster AJ, Fergusson D, Doucette S, van Walraven C . Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a systematic review and meta-analysis. CMAJ 2008; 179: 235–244.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Jowett S, Bryan S, Mahe I, Brieger D, Carlsson J, Kartman B et al. A multinational investigation of time and traveling costs in attending anticoagulation clinics. Value health 2008; 11: 207–212.

    Article  PubMed  Google Scholar 

  29. 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: 2282–2289.

    Article  CAS  PubMed  Google Scholar 

  30. Sullivan PW, Lawrence WF, Ghushchyan V . A national catalog of preference-based scores for chronic conditions in the United States. Med care 2005; 43: 736–749.

    Article  PubMed  Google Scholar 

  31. Gage BF, Cardinalli AB, Owens DK . The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch intern med 1996; 156: 1829–1836.

    Article  CAS  PubMed  Google Scholar 

  32. 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: 2063–2069.

    Article  CAS  PubMed  Google Scholar 

  33. NICE National Institute of Health and Care Excellence. Guide to the methods of technology appraisal 2013.

  34. International society for pharmacoeconomics and outcomes research

  35. Socialstyrelsen, Nationella riktlinjer för prostatacancersjukvård. Medicinskt och hälsoekonomiskt faktadokument. 2007: Stockholm.

  36. Fenwick E, Claxton K, Sculpher M . Representing uncertainty: the role of cost-effectiveness acceptability curves. Health econ 2001; 10: 779–787.

    Article  CAS  PubMed  Google Scholar 

  37. Verhoef TI, Redekop WK, Darba J, Geitona M, Hughes DA, Siebert U et al. A systematic review of cost-effectiveness analyses of pharmacogenetic-guided dosing in treatment with coumarin derivatives. Pharmacogenomics 2010; 11: 989–1002.

    Article  CAS  PubMed  Google Scholar 

  38. Mega JL, Walker JR, Ruff CT, Vandell AG, Nordio F, Deenadayalu N et al. Genetics and the clinical response to warfarin and edoxaban: findings from the randomised, double-blind ENGAGE AF-TIMI 48 trial. Lancet 2015; 385: 2280–2287.

    Article  CAS  PubMed  Google Scholar 

  39. Pink J, Pirmohamed M, Lane S, Hughes DA . Cost-effectiveness of pharmacogenetics-guided warfarin therapy vs. alternative anticoagulation in atrial fibrillation. Clin Pharmacol Ther 2014; 95: 199–207.

    Article  CAS  PubMed  Google Scholar 

  40. Plumpton CO, Roberts D, Pirmohamed M, Hughes DA . A systematic review of economic evaluations of pharmacogenetic testing for prevention of adverse drug reactions. Pharmacoeconomics 2016; doi: 10.1007/s40273-016-0397-9; e-pub ahead of print.

    Article  PubMed  Google Scholar 

  41. British National Formulary.

  42. Prisdatabas för läkemedel (2015)

  43. National Institute of Health and Clinical Excellence. Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation. Final appraisal determination. 2011.

  44. National Institute of Health and Clinical Excellence. Apixaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation. NICE technology appraisal guidance 275. 2013.

  45. SBU (2007). Självtestning och egenvård vid användning av blodproppsförebyggande läkemedel. SBU ALERT rapport, NR 2007-05.

  46. Department of Health. National schedule of reference costs 2013/14.

  47. Alberta Health and Wellness. Health costing in Alberta. Annual Report. Edmonton: 2006.

  48. Luengo-Fernandez R, Yiin GS, Gray AM, Rothwell PM . Population-based study of acute- and long-term care costs after stroke in patients with AF. Int j stroke 2013; 8: 308–314.

    Article  PubMed  Google Scholar 

  49. Ghatnekar O, Carlsson KS Kostnader för insjuknande i stroke år 2009, en incidensbaserad studie. IHE RAPPORT 2012: 2.

  50. Schwander B, Gradl B, Zollner Y, Lindgren P, Diener HC, Luders S et al. Cost-utility analysis of eprosartan compared to enalapril in primary prevention and nitrendipine in secondary prevention in Europe—the HEALTH model. Value health 2009; 12: 857–871.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to M Pirmohamed.

Ethics declarations

Competing interests

This work was supported by the European Community's Seventh Framework Programme under grant agreement HEALTH-F2-2009-223062. Dr Verhoef, Dr Maitland-van der Zee, Dr Wadelius and Dr Pirmohamed report grants from EU Commission FP7 programme, during the conduct of the study; Dr Wadelius reports grants from the Swedish Research Council (Medicine), grants from the Swedish Heart and Lung Foundation, grants from the Clinical Research Support at Uppsala University, during the conduct of the study; Dr Pirmohamed is an NIHR Senior Investigator; and as part of the EU-PACT trial, we worked with LGC (a UK-based company) who were a partner on the project, and developed the point-of-care platform which was used for genotyping in the trial, and on which the results of this cost-effectiveness paper are based. However, we did not receive any funding directly from LGC.

Additional information

Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website

Supplementary information

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Verhoef, T., Redekop, W., Langenskiold, S. et al. Cost-effectiveness of pharmacogenetic-guided dosing of warfarin in the United Kingdom and Sweden. Pharmacogenomics J 16, 478–484 (2016).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links