Skip to main content
SpringerLink
Log in

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

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  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):2370–2375

    Article  CAS  Google Scholar 

  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):263–272

    Article  Google Scholar 

  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):1093–1100

    Article  Google Scholar 

  4. Chatap G, Giraud K, Vincent JP (2002) Atrial fibrillation in the elderly: facts and management. Drugs Aging 19(11):819–846

    Article  Google Scholar 

  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):2893–2962

    Article  Google Scholar 

  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):857–864

    Article  Google Scholar 

  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):66–73

    Article  CAS  Google Scholar 

  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):922–923

    Article  Google Scholar 

  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):207–214

    Article  CAS  Google Scholar 

  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):297–305

    Article  Google Scholar 

  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):827–837

    Article  Google Scholar 

  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):3238–3249

    PubMed  CAS  Google Scholar 

  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):67–75

    Article  CAS  Google Scholar 

  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):3961–3967

    PubMed  CAS  Google Scholar 

  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):493–503

    Article  CAS  Google Scholar 

  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):1176–1183

    Article  Google Scholar 

  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):837–847

    Article  Google Scholar 

  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):e005657

    Article  Google Scholar 

  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 132:749–757

    Article  CAS  Google Scholar 

  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 281:56–61

    Article  Google Scholar 

  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):1577–1583

    Article  Google Scholar 

  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):e002758

    Article  Google Scholar 

  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):149–156

    Article  CAS  Google Scholar 

  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):566–572

    PubMed  PubMed Central  CAS  Google Scholar 

  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):146–147

    Article  Google Scholar 

  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):37–47

    Article  Google Scholar 

  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):955–962

    Article  CAS  Google Scholar 

  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):2450–2458

    Article  CAS  Google Scholar 

  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):150–159

    Article  CAS  Google Scholar 

  30. Lip GY (2015) Nonsteroidal anti-inflammatory drugs and bleeding risk in anticoagulated patients with atrial fibrillation. Expert Rev Cardiovasc Ther 13(9):963–965

    Article  CAS  Google Scholar 

  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):255–267

    Article  CAS  Google Scholar 

  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):625–635

    Article  CAS  Google Scholar 

  33. Fanikos J, Burnett AE, Mahan CE, Dobesh PP (2017) Renal function considerations for stroke prevention in atrial fibrillation. Am J Med 130(9):1015–1023

    Article  Google Scholar 

  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):2599–2604

    Article  CAS  Google Scholar 

Download references

Funding

No funding was received for this work.

Author information

Authors and Affiliations

  1. Chair of Cardiology, Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli” – Monaldi Hospital, Piazzale Ettore Ruggeri, 80131, Naples, Italy

    Vincenzo Russo, Marco Di Maio, Andreina Carbone, Anna Rago, Paolo Golino & Gerardo Nigro

  2. Department of Cardiology, Health Authority Naples 2 Nord, Naples, Italy

    Emilio Attena

  3. Cardiovascular Centre, Health Authority 1, Trieste, Italy

    Carmine Mazzone

  4. Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy

    Valentina Parisi

  5. Departmental Unit of Electrophysiology, Evaluation and Treatment of Arrhythmias, Monaldi Hospital, Naples, Italy

    Antonio D’Onofrio

Authors
  1. Vincenzo Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emilio Attena
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marco Di Maio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carmine Mazzone
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andreina Carbone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Valentina Parisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anna Rago
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Antonio D’Onofrio
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Paolo Golino
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gerardo Nigro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vincenzo Russo.

Ethics declarations

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.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Russo, V., Attena, E., Di Maio, M. et al. Clinical profile of direct oral anticoagulants versus vitamin K anticoagulants in octogenarians with atrial fibrillation: a multicentre propensity score matched real-world cohort study. J Thromb Thrombolysis 49, 42–53 (2020). https://doi.org/10.1007/s11239-019-01923-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-019-01923-9

Keywords

Search

Navigation