Advertisement

European Journal of Clinical Pharmacology

, Volume 73, Issue 11, pp 1417–1425 | Cite as

Trends in use of warfarin and direct oral anticoagulants in atrial fibrillation in Norway, 2010 to 2015

  • Lars J Kjerpeseth
  • Hanne Ellekjær
  • Randi Selmer
  • Inger Ariansen
  • Kari Furu
  • Eva Skovlund
Pharmacoepidemiology and Prescription

Abstract

Purpose

Since 2011, several direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban) have been introduced as alternatives to warfarin for stroke prophylaxis in atrial fibrillation. We wanted to investigate changes in utilization of oral anticoagulants for atrial fibrillation in Norway following the introduction of DOACs.

Methods

Using nationwide registries, we identified all adults with pharmacy dispensings for warfarin or DOACs between January 2010 and December 2015 in Norway, and used ambulatory reimbursement codes to identify atrial fibrillation as indication. We defined incident use by a 1-year washout period. We describe trends in prevalent and incident use of warfarin and DOACs between 2010 and 2015, as well as patterns of treatment switching for incident users.

Results

One hundred twenty-nine thousand two hundred eighty-five patients filled at least one prescription for an oral anticoagulant for atrial fibrillation; the yearly number of incident users increased from 262 to 421 per 100,000 person-years; and the yearly share of incident users who initiated a DOAC increased to 82%. Half the prevalent users were on a DOAC by 2015. Within a year of drug initiation, 6, 12, 16 and 20% of incident users of apixaban, rivaroxaban, warfarin and dabigatran, respectively, switched oral anticoagulant.

Conclusions

Use of DOACs for anticoagulation in atrial fibrillation became more prevalent between 2010 and 2015 in Norway, at the expense of warfarin.

Keywords

Atrial fibrillation Drug utilization Warfarin Dabigatran Rivaroxaban Apixaban 

Notes

Authors’ contribution

LJK and RS did the analyses. LJK wrote the manuscript. All authors helped plan and design the study, interpret findings and revise the manuscript. All authors approved the final version of the manuscript.

Compliance with ethical standards

The Regional Committee for Medical and Health Research Ethics in Central Norway approved the study protocol before the study commenced. The Norwegian Data Protection Authority gave a licence to link registry data.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2017_2296_MOESM1_ESM.pdf (171 kb)
Online resource 1 (PDF 171 kb)
228_2017_2296_MOESM2_ESM.pdf (167 kb)
Online resource 2 (PDF 166 kb)
228_2017_2296_MOESM3_ESM.pdf (166 kb)
Online resource 3 (PDF 166 kb)
228_2017_2296_MOESM4_ESM.pdf (176 kb)
Online resource 4 (PDF 175 kb)
228_2017_2296_MOESM5_ESM.pdf (533 kb)
Online resource 5 (PDF 532 kb)
228_2017_2296_MOESM6_ESM.pdf (175 kb)
Online resource 6 (PDF 174 kb)
228_2017_2296_MOESM7_ESM.pdf (172 kb)
Online resource 7 (PDF 171 kb)

References

  1. 1.
    Fuster V, Ryden LE, Asinger RW et al (2001) ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Circulation 104(17):2118–2150PubMedGoogle Scholar
  2. 2.
    Heeringa J, van der Kuip DA, Hofman A et al (2006) Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 27(8):949–953. doi: 10.1093/eurheartj/ehi825 CrossRefPubMedGoogle Scholar
  3. 3.
    Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S (2014) Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol 6:213–220. doi: 10.2147/CLEP.S47385 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Tveit A, Abdelnoor M, Enger S, Smith P (2008) Atrial fibrillation and antithrombotic therapy in a 75-year-old population. Cardiology 109(4):258–262. doi: 10.1159/000107789 CrossRefPubMedGoogle Scholar
  5. 5.
    Angell MS, Tiwari S, Løchen ML (2015) Prevalens og risikofaktorer for selvrapportert atrieflimmer hos menn og kvinner - Tromsøundersøkelsen [Prevalence and risk factors for self-reported atrial fibrillation in men and women—the Tromsø study]. Hjerteforum 28(4):36–42 NorwegianGoogle Scholar
  6. 6.
    Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE (2001) 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 285(18):2370–2375. doi: 10.1001/jama.285.18.2370 CrossRefPubMedGoogle Scholar
  7. 7.
    Krijthe BP, Kunst A, Benjamin EJ et al (2013) Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060. Eur Heart J 34(35):2746–2751. doi: 10.1093/eurheartj/eht280 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Chugh SS, Havmoeller R, Narayanan K et al (2014) Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation 129(8):837–847. doi: 10.1161/CIRCULATIONAHA.113.005119 CrossRefPubMedGoogle Scholar
  9. 9.
    Wolf PA, Abbott RD, Kannel WB (1991) Atrial fibrillation as an independent risk factor for stroke: the Framingham study. Stroke 22(8):983–988. doi: 10.1161/01.STR.22.8.983 CrossRefPubMedGoogle Scholar
  10. 10.
    Hart RG, Pearce LA, Aguilar MI (2007) Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 146(12):857–867. doi: 10.7326/0003-4819-146-12-200706190-00007 CrossRefPubMedGoogle Scholar
  11. 11.
    Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GY (2010) Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 123(7):638–645 e634. doi: 10.1016/j.amjmed.2009.11.025 CrossRefPubMedGoogle Scholar
  12. 12.
    Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361(12):1139–1151. doi: 10.1056/NEJMoa0905561 CrossRefPubMedGoogle Scholar
  13. 13.
    Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883–891. doi: 10.1056/NEJMoa1009638 CrossRefPubMedGoogle Scholar
  14. 14.
    Granger CB, Alexander JH, McMurray JJ et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365(11):981–992. doi: 10.1056/NEJMoa1107039 CrossRefPubMedGoogle Scholar
  15. 15.
    Wallentin L, Yusuf S, Ezekowitz MD et al (2010) 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 376(9745):975–983. doi: 10.1016/S0140-6736(10)61194-4 CrossRefPubMedGoogle Scholar
  16. 16.
    Singer DE, Hellkamp AS, Piccini JP et al (2013) Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy: data from the ROCKET AF clinical trial. J Am Heart Assoc 2(1):e000067. doi: 10.1161/JAHA.112.000067 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wallentin L, Lopes RD, Hanna M et al (2013) Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation 127(22):2166–2176. doi: 10.1161/CIRCULATIONAHA.112.142158 CrossRefPubMedGoogle Scholar
  18. 18.
    Stollberger C, Finsterer J (2013) Concerns about the use of new oral anticoagulants for stroke prevention in elderly patients with atrial fibrillation. Drugs Aging 30(12):949–958. doi: 10.1007/s40266-013-0119-3 CrossRefPubMedGoogle Scholar
  19. 19.
    Opstelten W, van den Donk M, Kuijpers T, Burgers J (2015) New oral anticoagulants for nonvalvular atrial fibrillation in the elderly: limited applicability in primary care. Eur J Gen Pract 21(2):145–149. doi: 10.3109/13814788.2014.989986 CrossRefPubMedGoogle Scholar
  20. 20.
    Camm AJ, Lip GY, De Caterina R et al (2012) 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation—developed with the special contribution of the European Heart Rhythm Association. Europace 14(10):1385–1413. doi: 10.1093/europace/eus305 CrossRefPubMedGoogle Scholar
  21. 21.
    January CT, Wann LS, Alpert JS et al (2014) 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 64(21):e1–76. doi: 10.1016/j.jacc.2014.03.022 CrossRefPubMedGoogle Scholar
  22. 22.
    Kirchhof P, Benussi S, Kotecha D et al (2016) 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37(38):2893–2962. doi: 10.1093/eurheartj/ehw210 CrossRefPubMedGoogle Scholar
  23. 23.
    Norsk selskap for trombose og hemostase (2013) Retningslinjer for antitrombotisk behandling og profylakse [Norwegian Society of Thrombosis and Haemostasis (2013) Guidelines on antithrombotic therapy and prophylaxis]. MagicApp. https://www.magicapp.org/app#/guideline/1. Accessed 27 June 2017. Norwegian
  24. 24.
    O'Brien EC, Kim S, Hess PL, Kowey PR, Fonarow GC, Piccini JP, Peterson ED (2015) Effect of the 2014 atrial fibrillation guideline revisions on the proportion of patients recommended for oral anticoagulation. JAMA Intern Med 175(5):848–850. doi: 10.1001/jamainternmed.2015.13 CrossRefPubMedGoogle Scholar
  25. 25.
    Komen J, Forslund T, Hjemdahl P, Andersen M, Wettermark B (2017) Effects of policy interventions on the introduction of novel oral anticoagulants in Stockholm: an interrupted time series analysis. Br J Clin Pharmacol 83(3):642–652. doi: 10.1111/bcp.13150 CrossRefPubMedGoogle Scholar
  26. 26.
    Furu K (2008) Establishment of the nationwide Norwegian Prescription Database (NorPD)—new opportunities for research in pharmacoepidemiology in Norway. Nor J Epidemiol 18(2):129–136Google Scholar
  27. 27.
    Furu K, Wettermark B, Andersen M, Martikainen JE, Almarsdottir AB, Sorensen HT (2010) The Nordic countries as a cohort for pharmacoepidemiological research. Basic Clin Pharmacol Toxicol 106(2):86–94. doi: 10.1111/j.1742-7843.2009.00494.x CrossRefPubMedGoogle Scholar
  28. 28.
    World Health Organization (1992) International Statistical Classification of Diseases and Related Health Problem - 10th revisionGoogle Scholar
  29. 29.
    Wonca International Classification Committee (1998) International Classification of Primary Care - 2nd EditionGoogle Scholar
  30. 30.
    Hallas J, Gaist D, Bjerrum L (1997) The waiting time distribution as a graphical approach to epidemiologic measures of drug utilization. Epidemiology 8(6):666–670CrossRefPubMedGoogle Scholar
  31. 31.
    Staerk L, Fosbol EL, Gadsboll K et al (2016) Non-vitamin K antagonist oral anticoagulation usage according to age among patients with atrial fibrillation: temporal trends 2011-2015 in Denmark. Sci Rep 6:31477. doi: 10.1038/srep31477 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Huisman MV, Rothman KJ, Paquette M et al (2017) The changing landscape for stroke prevention in AF: findings from the GLORIA-AF Registry phase 2. J Am Coll Cardiol 69(7):777–785. doi: 10.1016/j.jacc.2016.11.061 CrossRefPubMedGoogle Scholar
  33. 33.
    Pancholy SB, Sharma PS, Pancholy DS, Patel TM, Callans DJ, Marchlinski FE (2014) Meta-analysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants. Am J Cardiol 113(3):485–490. doi: 10.1016/j.amjcard.2013.10.035 CrossRefPubMedGoogle Scholar
  34. 34.
    Hellfritzsch M, Husted SE, Grove EL et al (2017) Treatment changes among users of non-vitamin K antagonist oral anticoagulants in atrial fibrillation. Basic Clin Pharmacol Toxicol 120(2):187–194. doi: 10.1111/bcpt.12664 CrossRefPubMedGoogle Scholar
  35. 35.
    Beyer-Westendorf J, Forster K, Ebertz F et al (2015) Drug persistence with rivaroxaban therapy in atrial fibrillation patients-results from the Dresden non-interventional oral anticoagulation registry. Europace 17(4):530–538. doi: 10.1093/europace/euu319 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Beyer-Westendorf J, Ebertz F, Forster K et al (2015) Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost 113(6):1247–1257. doi: 10.1160/TH14-11-0954 CrossRefPubMedGoogle Scholar
  37. 37.
    Heidbuchel H, Verhamme P, Alings M et al (2015) Updated European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 17(10):1467–1507. doi: 10.1093/europace/euv309 CrossRefPubMedGoogle Scholar
  38. 38.
    Beyer-Westendorf J, Gelbricht V, Forster K et al (2014) Safety of switching from vitamin K antagonists to dabigatran or rivaroxaban in daily care—results from the Dresden NOAC registry. Br J Clin Pharmacol 78(4):908–917. doi: 10.1111/bcp.12391 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ramm J (2013) Eldres bruk av helse- og omsorgstjenester [Health and care. Use of services among the elderly]. Stat Anal 137:93–100 NorwegianGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway
  2. 2.Department of NeuroscienceNorwegian University of Science and TechnologyTrondheimNorway
  3. 3.Stroke Unit, Department of Internal MedicineSt. Olav’s HospitalTrondheimNorway
  4. 4.Norwegian Institute of Public HealthOsloNorway

Personalised recommendations