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Direct oral anticoagulant use and the incidence of bleeding in the very elderly with atrial fibrillation

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Abstract

Atrial fibrillation (AF) is a major risk factor for stroke in the elderly population. The use of anticoagulation in patients with AF greatly reduces the risk for stroke, but results in an increased risk of bleeding. Over the past several years, direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, and apixaban) have been used in place of warfarin for stroke prevention in AF. We conducted a retrospective cohort study to assess the safety of DOACs in very elderly patients (75+) managed in a health care system encompassing both community and academic settings. We found that 36 % of patients had moderate to severe renal failure (estimated glomerular filtration rate <59 ml/min/1.73 m2) at the time of DOAC initiation. 142 patients were followed for a mean of 2.56 years, and five experienced a major bleeding episode while on anticoagulation, for a rate of 1.37 per 100 person years. All major bleeding episodes were associated with a decline in GFR compared to baseline. There were 12 non-major bleeding episodes reported. HAS-BLED scores were similar for those patients who experienced bleeding complications compared to those who did not. 21 % of patients were prescribed an inappropriately low dose of DOAC based on approved recommendations. DOACs appear to be a safe form of anticoagulation in very elderly patients with AF. However, the decline in GFR among patients with major bleeding highlights the importance of routine renal function monitoring.

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References

  1. Go AS et al (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

    Article  CAS  PubMed  Google Scholar 

  2. Reiffel JA (2014) Atrial fibrillation and stroke: epidemiology. Am J Med 127(4):e15–e16

    CAS  Google Scholar 

  3. Suarez Fernandez C et al (2015) Antithrombotic treatment in elderly patients with atrial fibrillation: a practical approach. BMC Cardiovasc Disord 15:143

    Article  PubMed  PubMed Central  Google Scholar 

  4. Connolly SJ et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361(12):1139–1151

    Article  CAS  PubMed  Google Scholar 

  5. Patel MR et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883–891

    Article  CAS  PubMed  Google Scholar 

  6. Granger CB et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365(11):981–992

    Article  CAS  PubMed  Google Scholar 

  7. Giugliano RP et al (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369(22):2093–2104

    Article  CAS  PubMed  Google Scholar 

  8. Halperin JL et al (2014) Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation 130(2):138–146

    Article  CAS  PubMed  Google Scholar 

  9. Eikelboom JW et al (2011) Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation 123(21):2363–2372

    Article  CAS  PubMed  Google Scholar 

  10. Halvorsen S 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):1864–1872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lip GY et al (2011) Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly) score. J Am Coll Cardiol 57(2):173–180

    Article  CAS  PubMed  Google Scholar 

  12. Schulman S et al (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3(4):692–694

    Article  CAS  PubMed  Google Scholar 

  13. Mant J 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):493–503

    Article  CAS  PubMed  Google Scholar 

  14. Scowcroft AC, Lee S, Mant J (2013) Thromboprophylaxis of elderly patients with AF in the UK: an analysis using the general practice research database (GPRD) 2000-2009. Heart 99(2):127–132

    Article  PubMed  Google Scholar 

  15. Rosenman MB et al (2012) Why is warfarin underused for stroke prevention in atrial fibrillation? A detailed review of electronic medical records. Curr Med Res Opin 28(9):1407–1414

    Article  CAS  PubMed  Google Scholar 

  16. Sharma M et al (2015) Efficacy and harms of direct oral anticoagulants in the elderly for stroke prevention in atrial fibrillation and secondary prevention of venous thromboembolism: systematic review and meta-analysis. Circulation 132(3):194–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ng KH et al (2016) Efficacy and safety of apixaban compared with aspirin in the elderly: a subgroup analysis from the AVERROES trial. Age Ageing 45(1):77–83

    Article  PubMed  Google Scholar 

  18. Camm AJ et al (2016) XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 37(14):1145–1153

    Article  PubMed  Google Scholar 

  19. Tamayo S et al (2015) Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a pharmacovigilance study of 27 467 patients taking rivaroxaban. Clin Cardiol 38(2):63–68

    Article  PubMed  Google Scholar 

  20. Abraham NS et al (2015) Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ 350:h1857

    Article  PubMed  PubMed Central  Google Scholar 

  21. Pasca S et al (2015) Direct oral anticoagulants for very elderly people with atrial fibrillation: efficacy and safe enough? Clin Appl Thromb Hemost. doi:10.1177/1076029615619485

    Google Scholar 

  22. Gladstone DJ et al (2015) How to monitor patients receiving direct oral anticoagulants for stroke prevention in atrial fibrillation: a practice tool endorsed by thrombosis Canada, the Canadian Stroke Consortium, the Canadian Cardiovascular Pharmacists Network, and the Canadian Cardiovascular Society. Ann Intern Med 163(5):382–385

    Article  PubMed  Google Scholar 

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Acknowledgments

Funding for Fatima Khan, M.B.B.S., was supported by National Institutes of Health T32 Hematology research training Grant (5T32HL00706). Research reported in this publication was supported in part by Grant number UL1TR000114 from the National Center for Advancing Translational Sciences of the National Institutes of Health. The clinical data was provided by the University of Minnesota’s Informatics Consulting Service.

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Correspondence to Yvonne H. Datta.

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All authors declare no conflicting financial interest.

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This study was conducted with the approval of the University of Minnesota Institutional Review Board.

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Khan, F., Huang, H. & Datta, Y.H. Direct oral anticoagulant use and the incidence of bleeding in the very elderly with atrial fibrillation. J Thromb Thrombolysis 42, 573–578 (2016). https://doi.org/10.1007/s11239-016-1410-z

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