Skip to main content
SpringerLink
Log in

Meta-analysis of Safety and Efficacy of Anticoagulation versus no Anticoagulation in Octogenarians and Nonagenarians with Atrial Fibrillation

  • Original article
  • Published:
High Blood Pressure & Cardiovascular Prevention Aims and scope Submit manuscript

Abstract

Introduction

The role of anticoagulation in octogenarians and nonagenarians with atrial fibrillation (AF) is controversial due to the lack of evidence from randomized controlled trials (RCTs), owing to the under representation of these patients in clinical trials.

Aim

In the present meta-analysis we aim at comparing the clinical benefits and risk of anticoagulation (AC) with no AC in octogenarians and nonagenarians.

Methods

We systematically searched MEDLINE/PubMed, EMBASE/Ovid, and Web of Science databases from the inception to October, 2020. Studies were eligible for inclusion if they met the following criteria: studies comparing AC with no AC in patients aged 80 or more for AF and reported thromboembolic events (TE) and bleeding outcomes. We used Mantel-Haenszel method with a Paule-Mandel estimator of Tau2 with Hartung Knapp-Sidik-Jonkman adjustment to estimate risk ratio (RR) with a 95% confidence interval (CI). Outlier analysis was used to adjust for statistical heterogeneity.

Results

A total of 10 observation studies and 1 RCT were included in the final analysis. There was no difference in the risk of TE with AC in octogenarians and nonagenarians compared with no AC, before [RR: 0.87, 95% CI 0.62–1.23, I2: 71%, GRADE confidence “very low”] and after [RR: 0.83, 95% CI 0.66–1.04, I2: 55.5%] adjusting for statistical heterogeneity among studies. In the unadjusted analysis, no difference in the risk of bleeding events was observed between both groups [RR: 1.05, 95% CI 0.62–1.77, I2: 86%, GRADE confidence “very low”]. After adjusting for heterogeneity, AC was associated with an increased risk of bleeding compared with those not receiving AC [RR: 1.57, 95% CI 1.44–1.71, I2: 0%]. AC in octogenarians was not associated with a net clinical benefit compared with no AC.

Conclusions

This meta-analysis did not demonstrate any difference in the risk TE in octogenarians and nonagenarians with AF on AC vs. no AC, in both the adjusted and unadjusted analyses. Also, the risk of bleeding events in the unadjusted analysis was similar between both groups. The adjusted analysis showed an increased risk of bleeding in the AC group compared with no AC group. More data is needed to establish safety and efficacy of AC in this vulnerable patient population. The results of this analysis should be interpreted with caution due to the observational nature of most studies included, and the only RCT reported lower rates of TE and similar risk of bleeding.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JCJ, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart R. J Am Coll Cardiol. 2019;74:104–32.

    Article  Google Scholar 

  2. Balaghi-Inalou M, Parsa SA, Gachkar L, Andalib S. Anticoagulant therapy in atrial fibrillation for stroke prevention: assessment of agreement between clinicians’ decision and CHA2DS2-VASc and HAS-BLED Scores. High Blood Press Cardiovasc Prev. 2018;25:61–4.

    Article  Google Scholar 

  3. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al. The 2018 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39:1330–93.

    Article  CAS  Google Scholar 

  4. Andrade JG, Verma A, Mitchell LB, Parkash R, Leblanc K, Atzema C, et al. 2018 focused update of the canadian cardiovascular society guidelines for the management of atrial fibrillation. Can J Cardiol. 2018;34:1371–92.

    Article  Google Scholar 

  5. Skripka A, Sychev D, Bochkov P, Shevchenko R, Krupenin P, Kogay V, et al. Factors affecting trough plasma dabigatran concentrations in patients with atrial fibrillation and chronic kidney disease. High Blood Press Cardiovasc Prev. 2020;27:151–6.

    Article  CAS  Google Scholar 

  6. Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke. 2005;36:1588–93.

    Article  Google Scholar 

  7. Hughes M, Lip GYH. Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. QJM. 2007;100:599–607.

    Article  CAS  Google Scholar 

  8. Glazer NL, Dublin S, Smith NL, French B, Jackson LA, Hrachovec JB, et al. Newly detected atrial fibrillation and compliance with antithrombotic guidelines. Arch Intern Med. 2007;167:246–52.

    Article  Google Scholar 

  9. Mant J, Hobbs FDR, Fletcher K, Roalfe A, Fitzmaurice D, Lip GYH, et al. 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. 2007;370:493–503.

    Article  CAS  Google Scholar 

  10. Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, et al. RE-LY Dabigatran vs Warfarin AF. N Engl J Med. 2013;368:2355–65.

    Article  CAS  Google Scholar 

  11. McKenzie JE, Salanti G, Lewis SC, Altman DG. Meta-analysis and The Cochrane Collaboration: 20 years of the Cochrane Statistical Methods Group. Syst Rev. 2013;2:80.

    Article  Google Scholar 

  12. Sterne JAC, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.

    Article  Google Scholar 

  13. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

    Article  Google Scholar 

  14. Singer DE, Chang Y, Go AS. The net clinical benefit of warfarin anticoagulation in atrial fibrillation [4]. Ann Intern Med. 2010;152:265.

    Article  Google Scholar 

  15. Alnsasra H, Haim M, Senderey AB, Reges O, Leventer-Roberts M, Arnson Y, et al. Net clinical benefit of anticoagulant treatments in elderly patients with nonvalvular atrial fibrillation: experience from the real world. Hear Rhythm. 2019;16:31–7.

    Article  Google Scholar 

  16. Peter A, Bahman F, Andreas T, Signild Å. To treat or not to treat. Stroke. 2017;48:1617–23.

    Article  Google Scholar 

  17. Okumura K, Akao M, Yoshida T, Kawata M, Okazaki O, Akashi S, et al. Low-dose edoxaban in very elderly patients with atrial fibrillation. N Engl J Med. 2020;15:1–11.

    Google Scholar 

  18. Bertozzo G, Zoppellaro G, Granziera S, Marigo L, Rossi K, Petruzzellis F, et al. Reasons for and consequences of vitamin K antagonist discontinuation in very elderly patients with non-valvular atrial fibrillation. J Thromb Haemost. 2016;14:2124–31.

    Article  CAS  Google Scholar 

  19. Chao TF, Liu CJ, Lin YJ, Chang SL, Lo LW, Hu YF, et al. Oral anticoagulation in very elderly patients with atrial fibrillation: A nationwide cohort study. Circulation. 2018;138:37–47.

    Article  Google Scholar 

  20. Ekerstad N, Karlsson T, Söderqvist S, Karlson BW. Hospitalized frail elderly patients—atrial fibrillation, anticoagulation and 12 months’ outcomes. Clin Interv Aging. 2018;13:749–56.

    Article  CAS  Google Scholar 

  21. Kodani E, Atarashi H, Inoue H, Okumura K, Yamashita T, Origasa H. Use of warfarin in elderly patients with non-valvular atrial fibrillation – Subanalysis of the J-RHYTHM registry. Circ J. 2015;79:2345–52.

    Article  CAS  Google Scholar 

  22. Patti G, Lucerna M, Pecen L, Siller-Matula JM, Cavallari I, Kirchhof P, et al. 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. 2017;6:89.

    Article  Google Scholar 

  23. Raposeiras-Roubín S, Alonso Rodríguez D, Camacho Freire SJ, Abu-Assi E, Cobas-Paz R, Rodríguez Pascual C, et al. Vitamin K antagonists and direct oral anticoagulants in nonagenarian patients with atrial fibrillation. J Am Med Dir Assoc. 2020;21:367–73.

    Article  Google Scholar 

  24. Siu CW, Tse HF. Net clinical benefit of warfarin therapy in elderly chinese patients with atrial fibrillation. Circ Arrhythmia Electrophysiol. 2014;7:300–6.

    Article  CAS  Google Scholar 

  25. Yamashita Y, Hamatani Y, Esato M, Chun YH, Tsuji H, Wada H, et al. Clinical characteristics and outcomes in extreme elderly (age ≥ 85 years) Japanese patients with atrial fibrillation: The Fushimi AF registry. Chest. 2016;149:401–12.

    Article  Google Scholar 

  26. Ng KH, Shestakovska O, Connolly SJ, Eikelboom JW, Avezum A, Diaz R, et al. Efficacy and safety of apixaban compared with aspirin in the elderly: a subgroup analysis from the AVERROES trial. Age Ageing. 2016;45:77–83.

    Article  Google Scholar 

  27. Chan YH, Lee KT, Kao YW, Huang CY, Chen YL, Hang SCL, et al. The comparison of non-Vitamin K antagonist oral anticoagulants versus well-managed warfarin with a lower INR target of 1.5 to 2.5 in Asians patients with non-valvular atrial fibrillation. PLoS ONE. 2019;14:1–16.

    Google Scholar 

  28. Brook R, Aswapanyawongse O, Tacey M, Kitipornchai T, Ho P, Lim HY. Real-world direct oral anticoagulants experience in atrial fibrillation: falls risk and low dose anticoagulation are predictive of both bleeding and stroke risk. Intern Med J. 2019;45:89.

    Google Scholar 

  29. Shen AYJ, Yao JF, Brar SS, Jorgensen MB, Chen W. Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol. 2007;50:309–15.

    Article  Google Scholar 

  30. Pandey AK, Xu K, Zhang L, Gupta S, Eikelboom J, Cook O, et al. Lower versus standard INR targets in atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials. Thromb Haemost. 2020;120:484–94.

    Article  Google Scholar 

  31. Chai-Adisaksopha C, Hillis C, Thabane L, Iorio A. A systematic review of definitions and reporting of bleeding outcome measures in haemophilia. Haemophilia. 2015;21:731–5.

    Article  CAS  Google Scholar 

  32. Rao MP, Vinereanu D, Wojdyla DM, Alexander JH, Atar D, Hylek EM, et al. Clinical outcomes and history of fall in patients with atrial fibrillation treated with oral anticoagulation: insights from the ARISTOTLE Trial. Am J Med. 2018;131:269–75.

    Article  Google Scholar 

  33. Chiu AS, Jean RA, Fleming M, Pei KY. Recurrent falls among elderly patients and the impact of anticoagulation therapy. World J Surg. 2018;42:3932–8.

    Article  Google Scholar 

  34. Pugh D, Pugh J, Mead GE. Attitudes of physicians regarding anticoagulation for atrial fibrillation: a systematic review. Age Ageing. 2011;40:675–83.

    Article  Google Scholar 

  35. Liuzzo G, Patrono C. Low-dose edoxaban for stroke prevention in elderly patients with atrial fibrillation: comment on the edoxaban low-dose for elder care atrial fibrillation patients (ELDERCARE-AF) trial. Eur Heart J. 2020;41:3882–3.

    Article  CAS  Google Scholar 

Download references

Funding

None

Author information

Author notes

  1. Kirolos Barssoum, Ashish Kumar and Samarthkumar Thakkar contributed equally in the manuscript.

Authors and Affiliations

  1. Department of Internal Medicine, Rochester Regional Health, Unity Hospital, Rochester, NY, USA

    Kirolos Barssoum, Osarenren Idemudia, Navya Akula & Mahmood Mubasher

  2. Department of Critical Care Medicine, St. John’s Medical College, Bangalore, India

    Ashish Kumar

  3. Department of Internal Medicine, Rochester General Hospital, Rochester, NY, USA

    Kirolos Barssoum, Samarthkumar Thakkar, Adnan Kharsa & Devesh Rai

  4. Department of Internal Medicine, LSU Health Sciences Center, Shreveport, LA, USA

    Aakash R. Sheth

  5. Department of Internal Medicine, Hackensack Meridian Health Palisades Medical Center, Bergen, NJ, USA

    Mounir Ibrahim

  6. Department of Internal Medicine, Louis A Weiss Memorial Hospital, Chicago, IL, USA

    Harsh P. Patel

  7. Rutgers New Jersey Medical School, Trinitas Regional Medical Center, Elizabeth, NJ, USA

    Ahmed Mowafy

  8. Division of Cardiovascular Disease, Loyola Stritch School of Medicine, Loyola University Medical Cemter, Maywood, IL, USA

    Ahmed Elkaryoni

  9. American University of Antigua, Antigua, Barbuda, USA

    Fadi Ibrahim

  10. Assiut University, Assiut, Egypt

    Kyrillos N. Ghattas

  11. Department of Cardiology, Sands-Constellation Heart Institute, Rochester Regional Health, Rochester, NY, USA

    Mohan Rao

Authors
  1. Kirolos Barssoum
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashish Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Samarthkumar Thakkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aakash R. Sheth
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Adnan Kharsa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mounir Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Devesh Rai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Osarenren Idemudia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Navya Akula
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Harsh P. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ahmed Mowafy
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ahmed Elkaryoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fadi Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Mahmood Mubasher
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Kyrillos N. Ghattas
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Mohan Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kirolos Barssoum.

Ethics declarations

Conflict of interest

None.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 88 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Barssoum, K., Kumar, A., Thakkar, S. et al. Meta-analysis of Safety and Efficacy of Anticoagulation versus no Anticoagulation in Octogenarians and Nonagenarians with Atrial Fibrillation. High Blood Press Cardiovasc Prev 28, 271–282 (2021). https://doi.org/10.1007/s40292-021-00442-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40292-021-00442-0

Keywords

Search

Navigation