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)
- 4.1k Downloads
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.
KeywordsAtrial Fibrillation Warfarin Dabigatran Rivaroxaban Apixaban
Funding was provided by Pfizer Germany.
All authors were responsible for critical revisions of the manuscript and for important intellectual content. All authors approved the final contents of the manuscript.
Compliance with Ethical Standards
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.
- 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.Google Scholar
- 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.Google Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Oxford Centre for Evidence-based Medicine. Levels of evidence (March 2009). 2009. Available from: http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/. Accessed 20 Jan 2017.
- 28.Dear doctors letter‘ on dabigatran, published 27 October, 2011. Available from: http://www.akdae.de/Arzneimittelsicherheit/RHB/Archiv/2011/20111027.pdf. Accessed 16 Apr 2017.