Clinical Research in Cardiology

, Volume 108, Issue 9, pp 1042–1052 | Cite as

Uptake in antithrombotic treatment and its association with stroke incidence in atrial fibrillation: insights from a large German claims database

  • Stefan H. HohnloserEmail author
  • Edin Basic
  • Michael Nabauer
Original Paper



Underuse of oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF) results in thousands of preventable strokes in Germany each year. This study aimed to assess changes in antithrombotic therapy in AF patients after increased use of direct oral anticoagulants (DOACs) in Germany and to evaluate whether the adoption of DOAC therapy was associated with changes in AF-related stroke and bleeding over time.


Analyses were carried out on a large claims-based dataset of 4 million health-insured Germans. The study population consisted of 601,261 prevalent AF patients between 2011 and 2016 who were assigned to one of the following four treatment groups: DOAC, VKA, antiplatelets or no antithrombotic treatment. Treatment patterns were descriptively analysed and represented by cohort and CHA2DS2-VASc score. Clinical outcomes before and after the adoption of DOAC therapy were assessed using Poisson regression models.


Use of OAC increased from 42 to 61% between 2011 and 2016, mainly due to more frequent prescription of DOACs. However, some underuse of OAC therapy remained even in high risk AF patients. In parallel with the increased prescription rate of OAC, there was an overall 24% incidence reduction in stroke between 2011 and 2016 which was mainly driven by reductions in ischemic strokes. Over the same time period the risk for major bleeding remained unchanged.


Between 2011 and 2016, the use of guideline-conform antithrombotic therapy in Germany has significantly increased. This was associated with a significant decline in strokes without an increased incidence of bleeding complications.


Atrial fibrillation Oral anticoagulation Direct oral anticoagulants VKA Stroke 



This study was sponsored by Bristol-Myers Squibb and Pfizer. Parts of the present publication have been presented at the European Society of Cardiology Congress 2018 as a poster presentation.

Compliance with ethical standards

Conflict of interest

Professor Hohnloser has served as a consultant for Bayer, BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo and Jansen. Professor Nabauer has received lecture fees from Bayer, BMS/Pfizer, Boehringer Ingelheim and Daiichi Sankyo. Dr. Basic is employee of Pfizer Deutschland GmbH. The authors have indicated that they have no other conflicts of interest regarding the content of this article.

Supplementary material

392_2019_1437_MOESM1_ESM.docx (34 kb)
Supplementary material 1 (DOCX 33 KB)


  1. 1.
    Ogilivie IM, Newton N, Welner SA, Cowell W, Lip GY (2010) Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 123:638–645CrossRefGoogle Scholar
  2. 2.
    Alamneh EA, Chalmers L, Bereznicki LR (2016) Suboptimal use of oral anticoagulants in atrial fibrillation: has the introduction of direct oral anticoagulants improved prescribing patterns? Am J Cardiovasc Drugs 16:183–200CrossRefGoogle Scholar
  3. 3.
    Steinberg BA, Gao H, Shrader P et al (2017) International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: results from the GARFIELD AF, ORBIT-AF I, and ORBIT AF II registries. Am Heart J 194:132–140CrossRefGoogle Scholar
  4. 4.
    Camm AJ, Accetta G, Ambrosio G et al (2017) Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation. Heart 103:307–314CrossRefGoogle Scholar
  5. 5.
    Gadsbøll K, Staerk L, Fosbøl EL, Sindet-Pedersen C, Gundlund A, Lip GY, Gislason GH, Olesen JB (2017) Increased use of oral anticoagulants in patients with atrial fibrillation: temporal trends from 2005 to 2015 in Denmark. Eur Heart J 38(12):899–906Google Scholar
  6. 6.
    Marzec LN, Wang J, Shah ND, Chan PS, Ting HH, Gosch KL, Hsu JC, Maddox TM (2017) Influence of direct oral anticoagulants on rates of oral anticoagulation for atrial fibrillation. J Am Coll Cardiol 69(20):2475–2484CrossRefGoogle Scholar
  7. 7.
    Cowan JC, Wu J, Hall M, Orlowski A, West RM, Gale CP (2018) A 10 year study of hospitalized atrial fibrillation-related stroke in England and its association with uptake of oral anticoagulation. Eur Heart J 39(32):2975–2983CrossRefGoogle Scholar
  8. 8.
    8 Forslund T, Komen JJ, Andersen M, Wettermark B, von Euler M, Mantel-Teeuwisse AK, Braunschweig F, Hjemdahl P (2018) Improved stroke prevention in atrial fibrillation after the introduction of non-vitamin K antagonist oral anticoagulants. Stroke 49(9):2122–2128CrossRefGoogle Scholar
  9. 9.
    Andersohn F, Walker J (2016) Characteristics and external validity of the German Health Risk Institute (HRI) Database: German Health Risk Institute (HRI) database. Pharmacoepidemiol Drug Saf 25:106–109CrossRefGoogle Scholar
  10. 10.
    Schnabel RB, Yin X, Gona P et al (2015) 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 386(9989):154–162CrossRefGoogle Scholar
  11. 11.
    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 37:2893–2962CrossRefGoogle Scholar
  12. 12.
    Zimny M, Blum S, Ammann P et al (2017) Uptake of non-vitamin K antagonist oral anti coagulants in patients with atrial fibrillation—a prospective cohort study. Swiss Med Wkly 147:w14410Google Scholar
  13. 13.
    van den Heuvel JM, Hövels AM, Büller HR, Mantel-Teeuwisse AK, de Boer A, Maitland-van der Zee AH (2018) NOACs replace VKA as preferred oral anticoagulant among new patients: a drug utilization study in 560 pharmacies in The Netherlands. Thromb J 16:7CrossRefGoogle Scholar
  14. 14.
    Huisman MV, Rothman KJ, Paquette M et al (2015) Antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation: the GLORIA-AF Registry, phase II. Am J Med 128(12):1306–1313CrossRefGoogle Scholar
  15. 15.
    Olesen JB, Lip GY, Hansen ML et al (2011) Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 31:342:d124Google Scholar
  16. 16.
    Diener HC, Aisenberg J, Ansell J et al (2017) Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2. Eur Heart J 38(12):860–868Google Scholar
  17. 17.
    Mant J, Hobbs FD, Fletcher K et al (2007) 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 370(9586):493–503CrossRefGoogle Scholar
  18. 18.
    Halvorsen S, Atar D, Yang H et al (2014) Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J 35(28):1864–1872CrossRefGoogle Scholar
  19. 19.
    Avgil-Tsadok M, Jackevicius CA, Essebag V, Eisenberg MJ, Rahme E, Behlouli H, Pilote L (2016) Dabigatran use in elderly patients with atrial fibrillation. Thromb Haemost 115(1):152–160CrossRefGoogle Scholar
  20. 20.
    Kato ET, Giugliano RP, Ruff CT et al (2016) Efficacy and safety of edoxaban in elderly patients with atrial fibrillation in the engage AF-TIMI 48 trial. J Am Heart Assoc 5(5):e003432CrossRefGoogle Scholar
  21. 21.
    Chao TF, Liu CJ, Li YJ et al (2018) Oral anticoagulation in very elderly patients with atrial fibrillation. A nationwide cohort study. Circulation 138(1):37–47CrossRefGoogle Scholar
  22. 22.
    Wyse DG, Waldo AL, DiMarco JP et al (2002) A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 347(23):1825–1833CrossRefGoogle Scholar
  23. 23.
    Chamberlain AM, Brown RD Jr, Alonso A, Gersh BJ, Killian JM, Weston SA, Roger VL (2016) No decline in the risk of stroke following incident atrial fibrillation since 2000 in the community: a concerning trend. J Am Heart Assoc 5(6): pii: e003408Google Scholar
  24. 24.
    Yiin GS, Howard DP, Paul NL, Li L, Mehta Z, Rothwell PM (2017) Recent time trends in incidence, outcome and premorbid treatment of atrial fibrillation-related stroke and other embolic vascular events: a population-based study. J Neurol Neurosurg Psychiatry 88(1):12–18CrossRefGoogle Scholar
  25. 25.
    Soo Y, Chan N, Leung KT, Chen XY, Mok V, Wong L, Leung T (2017) Age-specific trends of atrial fibrillation-related ischaemic stroke and transient ischaemic attack, anticoagulant use and risk factor profile in Chinese population: a 15-year study. J Neurol Neurosurg Psychiatry 88:744–748CrossRefGoogle Scholar
  26. 26.
    Guelker JE, Bufe A, Klues H, Shin DI, Blockhaus C, Gabriel NH, Haverkamp W, Kroeger K (2018) Trends in atrial fibrillation and prescription of oral anticoagulants and embolic strokes in Germany. Cardiovasc Revasc Med 21.
  27. 27.
    Krishnamurthi RV, Feigin VL, Forouzanfar MH et al (2013) Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health 1(5):e259–e281CrossRefGoogle Scholar
  28. 28.
    Ruff CT, Giugliano RP, Braunwald E et al (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383:955–962CrossRefGoogle Scholar
  29. 29.
    Hohnloser SH, Basic E, Hohmann C, Nabauer M (2018) Effectiveness and safety of non-vitamin K oral anticoagulants in comparison to phenprocoumon: data from 61,000 patients with atrial fibrillation. Thromb Haemost 118(3):526–538CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Stefan H. Hohnloser
    • 1
    Email author
  • Edin Basic
    • 2
  • Michael Nabauer
    • 3
  1. 1.Division Clinical Electrophysiology, Department of CardiologyJohann Wolfgang Goethe UniversityFrankfurtGermany
  2. 2.Pfizer Deutschland GmbHBerlinGermany
  3. 3.Department of CardiologyLudwig-Maximilians-UniversityMunichGermany

Personalised recommendations