European Geriatric Medicine

, Volume 9, Issue 2, pp 149–154 | Cite as

Evaluating the effectiveness and risks of oral anticoagulant treatments in multimorbid frail older subjects with atrial fibrillation using the multidimensional prognostic index: the EURopean study of older subjects with atrial fibrillation—EUROSAF

  • Nicola Veronese
  • Alessandra Argusti
  • Elisabetta Canepa
  • Maria Cristina Polidori
  • Stefania Maggi
  • Timo Strandberg
  • Alberto PilottoEmail author
  • EUROSAF Study Investigators
Research Paper



Previous studies suggested that a different risk of mortality may influence the oral anticoagulant prescription in older patients with atrial fibrillation (AF). Recently, the Multidimensional Prognostic Index (MPI) demonstrated a high grade of accuracy, calibration and feasibility to predict mortality in hospitalized and community-dwelling older people. Prognostic information, as calculated by the MPI, however, is not included in the decision algorithm of treatments in older patients with AF


The aim of this international multicenter prospective observational study was to evaluate whether a different prognostic profile, as determined by the MPI, is associated with different treatments for AF (no treatment vs oral anticoagulants) and differences in the main outcomes, i.e., mortality, major thromboembolic events and side effects.

Materials and methods

Older hospitalized patients (age ≥ 65 years) with non-valvular AF will be consecutively enrolled in an European, cross-national, prospective, observational study. At baseline, functional and clinical information will be collected to calculate the MPI, CHA2DS2-VASc score, HAS-BLED score, pharmacological treatments (and the compliance during follow-up) and main and secondary diagnoses. During the 12-month follow-up period, information on survival, major thromboembolic events and major bleeding will be collected. For these aims, a sample size of 3000 people was deemed as sufficient.


The EUROSAF study has the main objective of evaluating in a population of hospitalized older subjects with AF the clinical benefit/risk ratio of the oral anticoagulant treatments in terms of mortality, major thromboembolic events and bleeding side-effects, giving important information regarding the appropriate prescription of anticoagulant therapy in this population. Identifier



Atrial Fibrillation Muldimensional Prognostic Index Frailty Elderly Anticoagulants 



EUROSAF Study Investigators group also includes: Nicolò Marchionni, Florence, Italy; Mario Durando, Padova, Italy; Nicola Ferrara, Napoli, Italy; Mario Bò, Torino, Italy; Mario Barbagallo, Palermo, Italy; Giovanni Ruotolo, Catanzaro, Italy; Hans Jurgen Heppner, Schwelm, Germany; Philipp Bahrmann, Wiesbaden, Germany; Regina Roller-Wirnsberger, Vienna, Austria; Gil Gregorio Pedro, Madrid, Spain; Alfonso Cruz-Jentoft, Madrid, Spain; Pedro Marques da Silva, Lisboa, Portugal; Heidi Gruner, Lisboa, Portugal; Nicolas Berg, Liege, Belgium; Eva Topinkova, Prague, Czech Republic; Hana Matejovska-Kubesova, Brno, Czech Republic; Tuomo Nieminen, Helsinki and Lappeenranta, Finland; Laura Pikkarainen,Helsinki, Finland; Juhani Rossinen, Helsinki, Finland Marc Paccalin, Poitiers, France; Anna Kearney-Schwartz, Nancy, France; Krzyszof Rewiuk, Cracow, Poland; Francesco Mattace-Raso, Rotterdam, The Netherlands; Peter Olexa, Košice, Slovakia.


This is a study of the Comprehensive Geriatric Assessment (CGA)-Special Interest Group of the European Union Geriatric Medicine Society. Funding for this study was provided by an unrestricted contribution by Bayer Pharma AG.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest

Ethical approval

The study was approved by the Regione Liguria Ethics Committee, Genova, Italy. Registry Number 162REG2016, dated 08/06/2016, Section 2.

Informed consent

Informed consent will be obtained from all individual participants included in the study.


  1. 1.
    Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH et al (2013) Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 61(18):1935–1944CrossRefPubMedGoogle Scholar
  2. 2.
    Hylek EM, D’Antonio J, Evans-Molina C, Shea C, Henault LE, Regan S (2006) Translating the results of randomized trials into clinical practice: the challenge of warfarin candidacy among hospitalized elderly patients with atrial fibrillation. Stroke 37(4):1075–1080CrossRefPubMedGoogle Scholar
  3. 3.
    Maes F, Dalleur O, Henrard S, Wouters D, Scavee C, Spinewine A et al (2014) Risk scores and geriatric profile: can they really help us in anticoagulation decision making among older patients suffering from atrial fibrillation? Clin Interv Aging 9:1091–1099PubMedPubMedCentralGoogle Scholar
  4. 4.
    Pugh D, Pugh J, Mead GE (2011) Attitudes of physicians regarding anticoagulation for atrial fibrillation: a systematic review. Age Ageing 40(6):675–683CrossRefPubMedGoogle Scholar
  5. 5.
    Zarraga IG, Kron J (2013) Oral anticoagulation in elderly adults with atrial fibrillation: integrating new options with old concepts. J Am Geriatr Soc 61(1):143–150CrossRefPubMedGoogle Scholar
  6. 6.
    Sinnaeve PR, Brueckmann M, Clemens A, Oldgren J, Eikelboom J, Healey JS (2012) Stroke prevention in elderly patients with atrial fibrillation: challenges for anticoagulation. J Intern Med 271(1):15–24CrossRefPubMedGoogle Scholar
  7. 7.
    Barco S, Cheung YW, Eikelboom JW, Coppens M (2013) New oral anticoagulants in elderly patients. Best Pract Res Clin Haematol 26(2):215–224CrossRefPubMedGoogle Scholar
  8. 8.
    Sardar P, Chatterjee S, Chaudhari S, Lip GY (2014) New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials. J Am Geriatr Soc 62(5):857–864CrossRefPubMedGoogle Scholar
  9. 9.
    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):949–958CrossRefPubMedGoogle Scholar
  10. 10.
    Crome P, Lally F, Cherubini A, Oristrell J, Beswick AD, Clarfield AM et al (2011) Exclusion of older people from clinical trials: professional views from nine European countries participating in the PREDICT study. Drugs Aging 28(8):667–677CrossRefPubMedGoogle Scholar
  11. 11.
    Gill TM (2012) The central role of prognosis in clinical decision making. JAMA 307(2):199–200CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Pilotto A, Ferrucci L, Franceschi M, D’Ambrosio LP, Scarcelli C, Cascavilla L et al (2008) Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients. Rejuvenation Res 11(1):151–161CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Pilotto A, Gallina P, Fontana A, Sancarlo D, Bazzano S, Copetti M et al (2013) Development and validation of a multidimensional prognostic index for mortality based on a standardized multidimensional assessment schedule (MPI-SVaMA) in community-dwelling older subjects. J Am Med Dir Assoc 14(4):287–292CrossRefPubMedGoogle Scholar
  14. 14.
    Yourman LC, Lee SJ, Schonberg MA, Widera EW, Smith AK (2012) Prognostic indices for older adults: a systematic review. JAMA 307(2):182–192CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Siontis GC, Tzoulaki I, Ioannidis JP (2011) Predicting death: an empirical evaluation of predictive tools for mortality. Arch Intern Med 171(19):1721–1726CrossRefPubMedGoogle Scholar
  16. 16.
    Pilotto A, Rengo F, Marchionni N, Sancarlo D, Fontana A, Panza F et al (2012) Comparing the prognostic accuracy for all-cause mortality of frailty instruments: a multicentre 1-year follow-up in hospitalized older patients. PLoS One 7(1):e29090CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Gallucci M, Battistella G, Bergamelli C, Spagnolo P, Mazzuco S, Carlini A et al (2014) Multidimensional prognostic index in a cognitive impairment outpatient setting: mortality and hospitalizations. The Treviso Dementia (TREDEM) study. J Alzheimer’s Dis 42(4):1461–1468Google Scholar
  18. 18.
    Volpato S, Bazzano S, Fontana A, Ferrucci L, Pilotto A (2015) Multidimensional prognostic index predicts mortality and length of stay during hospitalization in the older patients: a multicenter prospective study. J Gerontol Ser A Biol Sci Med Sci 70(3):325–331CrossRefGoogle Scholar
  19. 19.
    Pilotto A, Sancarlo D, Daragjati J, Panza F (2015). Perspective: the challenge of clinical decision-making for drug treatment in older people. The role of multidimensional assessment and prognosis. Front Med 1:61.
  20. 20.
    Pilotto A, Sancarlo D, Polidori MC, Cruz-Jentoft AJ, Mattace-Raso F, Paccalin M et al (2015) The MPI_AGE European Project: using Multidimensional Prognostic Indices (MPI) to improve cost-effectiveness of interventions in multimorbid frail older persons. Background, aim and design. Eur Geriatr Med 6(2):184–188CrossRefGoogle Scholar
  21. 21.
    Angleman SB, Santoni G, Pilotto A, Fratiglioni L, Welmer A-K (2015) Multidimensional prognostic index in association with future mortality and number of hospital days in a population-based sample of older adults: results of the EU Funded MPI_AGE Project. PloS one 10(7):e0133789CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Pilotto A, Gallina P, Copetti M, Pilotto A, Marcato F, Mello AM et al (2016) Warfarin treatment and all-cause mortality in community-dwelling older adults with atrial fibrillation: a retrospective observational study. J Am Geriatr Soc 64(7):1416–1424CrossRefPubMedGoogle Scholar
  23. 23.
    Granziera S, Cohen AT, Nante G, Manzato E, Sergi G (2015) Thromboembolic prevention in frail elderly patients with atrial fibrillation: a practical algorithm. J Am Med Dir Assoc 16(5):358–364CrossRefPubMedGoogle Scholar
  24. 24.
    Cerreta F, Eichler HG, Rasi G (2012) Drug policy for an aging population—the European Medicines Agency’s geriatric medicines strategy. N Engl J Med 367(21):1972–1974CrossRefPubMedGoogle Scholar
  25. 25.
    Kowal P, Dowd Edward, J (2001) Definition of an older person. Proposed working definition of an older person in Africa for the MDS ProjectGoogle Scholar
  26. 26.
    Olesen JB, Lip GY, Hansen ML, Hansen PR, Tolstrup JS, Lindhardsen J et al (2011) Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 342:d124CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY (2010) A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: The Euro Heart Survey. Chest 138(5):1093–1100CrossRefPubMedGoogle Scholar
  28. 28.
    Karamichalakis N, Letsas KP, Vlachos K, Georgopoulos S, Bakalakos A, Efremidis M et al (2015) Managing atrial fibrillation in the very elderly patient: challenges and solutions. Vasc Health Risk Manag 11:555–562PubMedPubMedCentralGoogle Scholar
  29. 29.
    Ng KH, Hart RG, Eikelboom JW (2013) Anticoagulation in patients aged ≥ 75 years with atrial fibrillation: role of novel oral anticoagulants. Cardiol Ther 2(2):135–149CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    McGrath ER, Go AS, Chang Y, Borowsky LH, Fang MC, Reynolds K et al (2017) Use of oral anticoagulant therapy in older adults with atrial fibrillation after acute ischemic stroke. J Am Geriatr Soc 65(2):241–248CrossRefPubMedGoogle Scholar
  31. 31.
    Veronese N, Stubbs B, Noale M, Solmi M, Pilotto A, Vaona A, et al (2017) Polypharmacy is associated with higher frailty risk in older people: an 8-year longitudinal cohort study. J Am Med Dir Assoc 18(7): 624–628CrossRefPubMedGoogle Scholar
  32. 32.
    Orkaby AR, Ozonoff A, Reisman JI, Miller DR, Zhao S, Rose AJ (2017) Continued use of warfarin in veterans with atrial fibrillation after dementia diagnosis. J Am Geriatr Soc 65(2):249–256CrossRefPubMedGoogle Scholar
  33. 33.
    Saheb Sharif-Askari F, Syed Sulaiman SA, Saheb Sharif-Askari N (2017) Anticoagulation therapy in patients with chronic kidney disease. Adv Exp Med Biol 906:101–114CrossRefPubMedGoogle Scholar
  34. 34.
    Lefebvre MC, St-Onge M, Glazer-Cavanagh M, Bell L, Kha Nguyen JN, Viet-Quoc Nguyen P et al (2016) The effect of bleeding risk and frailty status on anticoagulation patterns in octogenarians with atrial fibrillation: The FRAIL-AF Study. Can J Cardiol 32(2):169–176CrossRefPubMedGoogle Scholar

Copyright information

© European Geriatric Medicine Society 2018

Authors and Affiliations

  • Nicola Veronese
    • 1
  • Alessandra Argusti
    • 2
  • Elisabetta Canepa
    • 1
  • Maria Cristina Polidori
    • 3
  • Stefania Maggi
    • 4
  • Timo Strandberg
    • 5
    • 6
  • Alberto Pilotto
    • 1
    Email author
  • EUROSAF Study Investigators
  1. 1.Geriatrics Unit, Department of Geriatric Care, OrthoGeriatrics and Rehabilitation, Frailty Area, E.O. Galliera HospitalNational Relevance and High Specialization HospitalGenoaItaly
  2. 2.Scientific Coordination Unit, E.O. Galliera HospitalNational Relevance and High Specialization HospitalGenoaItaly
  3. 3.Ageing Clinical Research, Department Medicine IIUniversity Hospital of CologneCologneGermany
  4. 4.Neuroscience SectionEUGMS President and National Research CouncilPaduaItaly
  5. 5.University of Helsinki and Helsinki University HospitalHelsinkiFinland
  6. 6.Center for Life Course Health ResearchUniversity of OuluOuluFinland

Personalised recommendations