Skip to main content

Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial Fibrillation in Older People: Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016)



Age appropriateness of anticoagulants for stroke prevention in atrial fibrillation is uncertain.


To review oral anticoagulants for the treatment of atrial fibrillation in older (age >65 years) people and to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability using the Fit-fOR-The-Aged (FORTA) classification.


We performed a structured comprehensive review of controlled clinical trials and summaries of individual product characteristics to assess study and total patient numbers, quality of major outcome data and data of geriatric relevance. The resulting evidence was discussed in a round table with an interdisciplinary panel of ten European experts. Decisions on age appropriateness were made using a Delphi process.


For the eight drugs included, 380 citations were identified. The primary outcome results were reported in 32 clinical trials with explicit and relevant data on older people. Though over 24,000 patients aged >75/80 years were studied for warfarin, data on geriatric syndromes were rare (two studies reporting on frailty/falls/mental status) and missing for all other compounds. Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist oral anticoagulants (including low/high-intensity dabigatran and high-intensity edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon, acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting the absence of data.


All non-vitamin K antagonist oral anticoagulants and warfarin were classified as beneficial or very beneficial in older persons (FORTA-A or -B), underlining the overall positive assessment of the risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally used in Europe, the lack of evidence should challenge current practice.

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

Fig. 1


  1. 1.

    European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery, Camm AJ, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31:2369–429.

  2. 2.

    Wilke T, Groth A, Mueller S, et al. Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients. Europace. 2013;15:486–93.

    Article  PubMed  Google Scholar 

  3. 3.

    Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983–8.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857–67.

    Article  PubMed  Google Scholar 

  5. 5.

    Wehling M. Drug therapy in the elderly: too much or too little, what to do? A new assessment system: fit for the aged (FORTA) [in German]. Dtsch Med Wochenschr. 2008;133:2289–91.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Wehling M. Multimorbidity and polypharmacy: how to reduce the harmful drug load and yet add needed drugs in the elderly? Proposal of a new drug classification: fit for the aged. J Am Geriatr Soc. 2009;57:560–1.

    Article  PubMed  Google Scholar 

  7. 7.

    Kuhn-Thiel A, Weiss C. Wehling M; FORTA authors/expert panel members. Consensus validation of the FORTA (Fit fOR The Aged) list: a clinical tool for increasing the appropriateness of pharmacotherapy in the elderly. Drugs Aging. 2014;31:131–40.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Pazan F, Weiss C, Wehling M. The FORTA (Fit fOR The Aged) list 2015: update of a validated clinical tool for improved pharmacotherapy in the elderly. Drugs Aging. 2016;33:447–9.

    Article  PubMed  Google Scholar 

  9. 9.

    American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63:2227–46.

  10. 10.

    Wehling M. Older people, a plethora of drugs, and drug list approaches: useful, efficacious, or a waste of time? J Am Med Dir Assoc. 2016;17:1073–5.

    Article  PubMed  Google Scholar 

  11. 11.

    Wehling M, Burkhardt H, Kuhn-Thiel A, et al. VALFORTA: a randomized trial to validate the FORTA (Fit fOR The Aged) classification. Age Ageing. 2016;45:262–7.

    Article  PubMed  Google Scholar 

  12. 12.

    Oelke M, Becher K, Castro-Diaz D, et al. Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014). Age Ageing. 2015;44:745–55.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Oxford Centre for Evidence-based Medicine. Levels of evidence (March 2009). 2009. Available from: Accessed 20 Jan 2017.

  14. 14.

    Roy B, Desai RV, Mujib M, et al. Effect of warfarin on outcomes in septuagenarian patients with atrial fibrillation. Am J Cardiol. 2012;109:370–7.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Kalantarian S, Stern TA, Mansour M, Ruskin JN. Cognitive impairment associated with atrial fibrillation: a meta-analysis. Ann Intern Med. 2013;158:338–46.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    de Bruijn RFAG, Heeringa J, Wolters FJ, et al. Association between atrial fibrillation and dementia in the general population. JAMA Neurol. 2015;72:1288–94.

    Article  PubMed  Google Scholar 

  18. 18.

    Mavaddat N, Roalfe A, Fletcher K, et al. Warfarin versus aspirin for prevention of cognitive decline in atrial fibrillation: randomized controlled trial (Birmingham Atrial Fibrillation Treatment of the Aged Study). Stroke. 2014;45:1381–6.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Sherman DG, Kim SG, Boop BS, et al. Occurrence and characteristics of stroke events in the Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management (AFFIRM) study. Arch Intern Med. 2005;23(165):1185–91.

    Article  Google Scholar 

  20. 20.

    Barber M, Tait RC, Scott J, et al. Dementia in subjects with atrial fibrillation: hemostatic function and the role of anticoagulation. J Thromb Haemost. 2004;2:1873–8.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Tjia J, Field TS, Mazor KM, et al. Dementia and risk of adverse warfarin-related events in the nursing home setting. Am J Geriatr Pharmacother. 2012;10:323–30.

    Article  PubMed  Google Scholar 

  22. 22.

    Moffitt P, Lane DA, Park H, et al. Thromboprophylaxis in atrial fibrillation and association with cognitive decline: systematic review. Age Ageing. 2016;45:767–75.

    Article  PubMed  Google Scholar 

  23. 23.

    Perera V, Bajorek BV, Matthews S, Hilmer SN. The impact of frailty on the utilisation of antithrombotic therapy in older patients with atrial fibrillation. Age Ageing. 2009;38:156–62.

    Article  PubMed  Google Scholar 

  24. 24.

    Lefebvre MC, St-Onge M, Glazer-Cavanagh M, et al. The effect of bleeding risk and frailty status on anticoagulation patterns in octogenarians with atrial fibrillation: the FRAIL-AF Study. Can J Cardiol. 2016;32:169–76.

    Article  PubMed  Google Scholar 

  25. 25.

    Man-Son-Hing M, Nichol G, Lau A, et al. Choosing antithrombotic therapy for elderly patients who are at risk for falls. Arch Intern Med. 1999;159:677–85.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Boltz MM, Podany AB, Hollenbeak CS, Armen SB. Injuries and outcomes associated with traumatic falls in the elderly population on oral anticoagulant therapy. Injury. 2015;46:1765–71.

    Article  PubMed  Google Scholar 

  27. 27.

    Ezekowitz MD, Bridgers SL, James KE, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation: Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med. 1992;327:1406–12.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Dear doctors letter‘ on dabigatran, published 27 October, 2011. Available from: Accessed 16 Apr 2017.

  29. 29.

    Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2015;17:1467–507.

    Article  PubMed  Google Scholar 

Download references


Funding was provided by Pfizer Germany.

Author information




All authors were responsible for critical revisions of the manuscript and for important intellectual content. All authors approved the final contents of the manuscript.

Corresponding author

Correspondence to Martin Wehling.

Ethics declarations


Pfizer Pharma GmbH Germany supported the initial meeting by covering the costs for the venue, travel expenses and offering honoraria according to a fair market value, but had no influence on the contents or results.

Conflict of interest

MW received lecturing and consulting fees from Bristol Myers, LEO, Mundipharma, Novartis, Pfizer, Roche, Sanofi-Aventis, Shire, Pierre-Fabre, Polyphor, Otsuka and Novo-Nordisk. RC has sat on national advisory boards and received honoraria for this work from manufacturers of NOAC medications including Bayer, Boehringer Ingelheim, Daichii Sankyo and Pfizer. VG received lecturing and consulting fees from BMS/Pfizer and Boehringer-Ingelheim. OH received lecturing and consulting fees from Pfizer, Bristol Myers Squibb, Bayer, Novartis, Sanofi-Aventis, Daichi Sankyo, Servier, Leo Pharma, Boehringer Ingelheim and Vifor Pharma. RH received lecturing or consulting fees from Glaxo Smith Kline, Sanofi MSD Pasteur, Pfizer, Mundipharma, Novartis and Sanofi Aventis. PM received lecturing and consulting fees from Bayer, Boehringer Ingelheim, Daiichi-Sankyo and Pfizer/BMS. TQ is supported by a joint Stroke Association and Chief Scientist Office Fellowship; he has received research, travel and educational support from Boehringer Ingelheim, Bayer, Bristol Myers and Pfizer. DR received lecturing and consulting fees from BMS/Pfizer, Boehringer-Ingelheim, Bayer Healthcare, Daiichi-Sankyo, Servier, Astra Zeneca, Siemens Healthcare, Novartis, Amgen and Berlin Chemie. GS received lecturing and consulting fees from Nutricia, Pfizer, Servier and Sigma-Tau in the last 4 years. FV received lecturing and consulting fees from BMS/Pfizer, Boehringer-Ingelheim, Bayer Healthcare and Daiichi-Sankyo.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wehling, M., Collins, R., Gil, V.M. et al. Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial Fibrillation in Older People: Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016). Drugs Aging 34, 499–507 (2017).

Download citation


  • Atrial Fibrillation
  • Warfarin
  • Dabigatran
  • Rivaroxaban
  • Apixaban