Advertisement

Journal of Thrombosis and Thrombolysis

, Volume 49, Issue 1, pp 42–53 | Cite as

Clinical profile of direct oral anticoagulants versus vitamin K anticoagulants in octogenarians with atrial fibrillation: a multicentre propensity score matched real-world cohort study

  • Vincenzo RussoEmail author
  • Emilio Attena
  • Marco Di Maio
  • Carmine Mazzone
  • Andreina Carbone
  • Valentina Parisi
  • Anna Rago
  • Antonio D’Onofrio
  • Paolo Golino
  • Gerardo Nigro
Article
  • 226 Downloads

Abstract

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and its prevalence increases with age. Few data are available about the clinical performance of direct oral anticoagulant (DOACs) in patients aged ≥ 80 years with AF. The aim of our propensity score matched cohort study was to compare the safety and efficacy of DOACs versus well-controlled VKA therapy among octogenarians with AF in real life setting. Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation Research Database (NCT03760874), which includes all AF patients followed by the participating centers, through outpatient visits every 3 to 6 months. The database was queried for AF patients aged ≥ 80 years who received DOACs or VKAs treatment. The primary effectiveness endpoint was the occurrence of thromboembolic events (a composite of stroke, transient ischemic attack, systemic embolism); the primary safety endpoint was the occurrence of major bleeding; the secondary endpoint was all-cause mortality. The database query identified 774 AF patients aged ≥ 80 years treated with VKAs and 279 with DOACs. Propensity score (2:1) matching selected 252 DOAC and 504 VKA recipients. The mean follow-up was 31.07 ± 14.09 months. The incidence rate of thromboembolic events was 13.79 per 1000 person-years [14.80 in DOAC vs 13.34 in VKA group, Hazard Ratio 1.10; 95% confidence interval (CI) 0.49 to 2.45; P = 0.823]. The incidence rate of intracranial hemorrhage (ICH) was 8.06 per 1000 person-years (3.25 in DOAC vs 10.23 in VKA group, HR 0.33; 95% CI 0.07 to 1.45; P = 0.600). Through these incidence rates, we found a positive net clinical benefit (NCB) of DOACs over VKAs, equal to + 9.01. The incidence rate of all-cause mortality was 105.05 per 1000 person-years (74.67 in DOAC vs 118.67 in VKA group, Hazard Ratio 0.65; 95% CI 0.47 to 0.90; P = 0.010). The concomitant use of antiinflammatory drugs (HR 7.90; P < 0.001) were found to be independent predictor of major bleeding. Moreover, age (HR 1.17; P < 0.002) and chronic kidney disease (HR 0.34; P = 0.019) were found to be independently associated with thromboembolic events. In our study no significant difference in terms of both thromboembolic and major bleeding events, but a significant lower incidence of all-cause mortality, was detected in AF patients aged ≥ 80 years treated with DOACs vs VKAs.

Keywords

Atrial fibrillation Direct oral anticoagulant Octogenarians Net clinical benefit Effectiveness Safety Major bleeding Thromboembolic events 

Notes

Fundings

No funding was received for this work.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

The procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

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

References

  1. 1.
    Go AS, Hylek EM, Phillips KA 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):2370–2375CrossRefGoogle Scholar
  2. 2.
    Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ (2010) Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 137(2):263–272CrossRefGoogle Scholar
  3. 3.
    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):1093–1100CrossRefGoogle Scholar
  4. 4.
    Chatap G, Giraud K, Vincent JP (2002) Atrial fibrillation in the elderly: facts and management. Drugs Aging 19(11):819–846CrossRefGoogle Scholar
  5. 5.
    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(38):2893–2962CrossRefGoogle Scholar
  6. 6.
    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):857–864CrossRefGoogle Scholar
  7. 7.
    Verdecchia P, D'Onofrio A, Russo V et al (2019) Persistence on apixaban in atrial fibrillation patients: a retrospective multicentre study. J Cardiovasc Med 20(2):66–73CrossRefGoogle Scholar
  8. 8.
    Russo V, Rago A, D'Onofrio A, Nigro G (2017) The clinical performance of dabigatran in the Italian real-life experience. J Cardiovasc Med 18(11):922–923CrossRefGoogle Scholar
  9. 9.
    Russo V, Carbone A, Rago A, Golino P, Nigro G (2019) Direct oral anticoagulants in octogenarians with atrial fibrillation: it is never too late. J Cardiovasc Pharmacol 73(4):207–214CrossRefGoogle Scholar
  10. 10.
    Singer DE, Chang Y, Fang MC et al (2009) The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 151(5):297–305CrossRefGoogle Scholar
  11. 11.
    Marinigh R, Lip GY, Fiotti N, Giansante C, Lane DA (2010) Age as a risk factor for stroke in atrial fibrillation patients: implications for thromboprophylaxis. J Am Coll Cardiol 56(11):827–837CrossRefGoogle Scholar
  12. 12.
    Andreotti F, Rocca B, Husted S et al (2015) Antithrombotic therapy in the elderly: expert position paper of the European Society of Cardiology Working Group on Thrombosis. Eur Heart J 36(46):3238–3249PubMedGoogle Scholar
  13. 13.
    Russo V, Rago A, Proietti R et al (2017) Efficacy and safety of the target-specific oral anticoagulants for stroke prevention in atrial fibrillation: the real-life evidence. Ther Adv Drug Saf 8(2):67–75CrossRefGoogle Scholar
  14. 14.
    Russo V, Bianchi V, Cavallaro C et al (2015) Efficacy and safety of dabigatran in a "real-life" population at high thromboembolic and hemorrhagic risk: data from MonaldiCare registry. Eur Rev Med Pharmacol Sci 19(20):3961–3967PubMedGoogle Scholar
  15. 15.
    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
  16. 16.
    Kooistra HA, Calf AH, Piersma-Wichers M et al (2016) Risk of bleeding and thrombosis in patients 70 years or older using vitamin K antagonists. JAMA Intern Med 176(8):1176–1183CrossRefGoogle Scholar
  17. 17.
    Chugh SS, Havmoeller R, Narayanan K et al (2014) Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 129(8):837–847CrossRefGoogle Scholar
  18. 18.
    Patti G, Lucerna M, Pecen L et al (2017) Thromboembolic risk, bleeding outcomes and effect of different antithrombotic strategies in very elderly patients with atrial fibrillation: a sub-analysis from the PREFER in AF (PREvention oF Thromboembolic Events-European Registry in Atrial Fibrillation). J Am Heart Assoc 6(7):e005657CrossRefGoogle Scholar
  19. 19.
    Patti G, Pecen L, Lucerna M et al (2019) Net Clinical benefit of non-vitamin K antagonist vs vitamin k antagonist anticoagulants in elderly patients with atrial fibrillation. Am J Med 132:749–757CrossRefGoogle Scholar
  20. 20.
    Giustozzi M, Vedovati MC, Verso M et al (2019) Patients aged 90years or older with atrial fibrillation treated with oral anticoagulants: a multicentre observational study. Int J Cardiol 281:56–61CrossRefGoogle Scholar
  21. 21.
    Ruiz Ortiz M, Muniz J, Rana Miguez P et al (2018) Inappropriate doses of direct oral anticoagulants in real-world clinical practice: prevalence and associated factors. A subanalysis of the FANTASIIA Registry. Europace 20(10):1577–1583CrossRefGoogle Scholar
  22. 22.
    Sorensen R, Gislason G, Torp-Pedersen C et al (2013) Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study. BMJ open 3(5):e002758CrossRefGoogle Scholar
  23. 23.
    Howard M, Lipshutz A, Roess B et al (2017) Identification of risk factors for inappropriate and suboptimal initiation of direct oral anticoagulants. J Thromb Thrombolysis 43(2):149–156CrossRefGoogle Scholar
  24. 24.
    Kwon CH, Kim M, Kim J, Nam GB, Choi KJ, Kim YH (2016) Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation. J Geriatr Cardiol 13(7):566–572PubMedPubMedCentralGoogle Scholar
  25. 25.
    Chao TF, Lip GYH, Chen SA (2019) Response by Chao et al to Letter Regarding Article, "Oral Anticoagulation in Very Elderly Patients With Atrial Fibrillation: A Nationwide Cohort Study". Circulation 139(1):146–147CrossRefGoogle Scholar
  26. 26.
    Chao TF, Liu CJ, Lin YJ et al (2018) Oral anticoagulation in very elderly patients with atrial fibrillation: a nationwide cohort study. Circulation 138(1):37–47CrossRefGoogle Scholar
  27. 27.
    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(9921):955–962CrossRefGoogle Scholar
  28. 28.
    Chai-Adisaksopha C, Crowther M, Isayama T, Lim W (2014) The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood 124(15):2450–2458CrossRefGoogle Scholar
  29. 29.
    Amin A, Deitelzweig S, Jing Y et al (2014) Estimation of the impact of warfarin's time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials. J Thromb Thrombolysis 38(2):150–159CrossRefGoogle Scholar
  30. 30.
    Lip GY (2015) Nonsteroidal anti-inflammatory drugs and bleeding risk in anticoagulated patients with atrial fibrillation. Expert Rev Cardiovasc Ther 13(9):963–965CrossRefGoogle Scholar
  31. 31.
    Kent AP, Brueckmann M, Fraessdorf M et al (2018) Concomitant oral anticoagulant and nonsteroidal anti-inflammatory drug therapy in patients with atrial fibrillation. J Am Coll Cardiol 72(3):255–267CrossRefGoogle Scholar
  32. 32.
    Olesen JB, Lip GY, Kamper AL et al (2012) Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 367(7):625–635CrossRefGoogle Scholar
  33. 33.
    Fanikos J, Burnett AE, Mahan CE, Dobesh PP (2017) Renal function considerations for stroke prevention in atrial fibrillation. Am J Med 130(9):1015–1023CrossRefGoogle Scholar
  34. 34.
    Hart RG, Pearce LA, Asinger RW, Herzog CA (2011) Warfarin in atrial fibrillation patients with moderate chronic kidney disease. Clin J Am Soc Nephrol 6(11):2599–2604CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Vincenzo Russo
    • 1
    Email author
  • Emilio Attena
    • 2
  • Marco Di Maio
    • 1
  • Carmine Mazzone
    • 3
  • Andreina Carbone
    • 1
  • Valentina Parisi
    • 4
  • Anna Rago
    • 1
  • Antonio D’Onofrio
    • 5
  • Paolo Golino
    • 1
  • Gerardo Nigro
    • 1
  1. 1.Chair of Cardiology, Department of Translational Medical SciencesUniversity of Campania “Luigi Vanvitelli” – Monaldi HospitalNaplesItaly
  2. 2.Department of CardiologyHealth Authority Naples 2 NordNaplesItaly
  3. 3.Cardiovascular CentreTriesteItaly
  4. 4.Department of Translational Medical SciencesUniversity of Naples Federico IINaplesItaly
  5. 5.Departmental Unit of Electrophysiology, Evaluation and Treatment of ArrhythmiasMonaldi HospitalNaplesItaly

Personalised recommendations