Journal of Thrombosis and Thrombolysis

, Volume 45, Issue 4, pp 550–556 | Cite as

Direct oral anti-coagulants compared to vitamin-K antagonists in cardioversion of atrial fibrillation: an updated meta-analysis

  • Natale Daniele Brunetti
  • Nicola Tarantino
  • Luisa De Gennaro
  • Michele Correale
  • Francesco Santoro
  • Matteo Di Biase
Article

Abstract

Pharmacological or electrical cardioversion allows immediate symptoms improvement in the setting of paroxysmal or persistent atrial fibrillation (AF), although the periprocedural risk of systemic embolism should be considered. Recently, there was a great interest on the safety and efficacy of direct oral anticoagulants (DOACs) when used for the cardioversion of non-valvular AF. We performed a random-effects meta-analysis of patients undergoing both electrical and pharmacologic cardioversion for non-valvular AF in the RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48, X-VeRT, ENSURE-AF, and EMANATE trials. We assessed Mantel–Haenszel pooled estimates of risk ratios (RRs) and 95% confidence intervals (CIs) for stroke/systemic embolism (SSE) and major bleeding (MB) at follow-up. A total of 8564 patients have been included in the analysis. When compared with patients receiving vitamin-K antagonists (VKAs), patients receiving DOACs had a lower risk of SSE (RR 0.70, 95% CI 0.33–1.546, P = 0.34), as well as of MB (RR 0.86;,95% CI 0.47–1.58, P = 0.62), although both were non-significant. Funnel plot analysis showed, however, lower RRs with more recent ad hoc studies in comparison with registrational studies, even though statistical significance was not reached. DOACs are as effective and as safe as VKAs for thromboembolic prevention in non-valvular AF in the setting of cardioversion. There are differences, although non-significant, between registrational studies and studies enrolling exclusively patients undergoing cardioversion of AF.

Keywords

Cardioversion Major bleeding Meta-analysis Non-valvular atrial fibrillation Stroke Systemic embolism Warfarin 

Notes

Compliance with ethical standards

Conflict of interest

The authors have no potential conflict of interest to disclose.

References

  1. 1.
    Sandhu RK, Smigorowsky M, Lockwood E, Savu A, Kaul P, McAlister FA (2017) Impact of electrical cardioversion on quality of life for the treatment of atrial fibrillation. Can J Cardiol 33:450–455CrossRefPubMedGoogle Scholar
  2. 2.
    Missault L, Jordaens L, Gheeraert P, Adang L, Clement D (1994) Embolic stroke after unanticoagulated cardioversion despite prior exclusion of atrial thrombi by transoesophageal echocardiography. Eur Heart J 15:1279–1280CrossRefPubMedGoogle Scholar
  3. 3.
    Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K (2016) 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37:2893–2962CrossRefPubMedGoogle Scholar
  4. 4.
    January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, Jr., Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW (2014) 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 64(21):e1–e76CrossRefPubMedGoogle Scholar
  5. 5.
    Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L, RE-LY Steering Committee and Investigators (2009) Dabigatran versus Warfarin in patients with atrial fibrillation. N Engl J Med 361:1139–1151CrossRefPubMedGoogle Scholar
  6. 6.
    Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM, ROCKET AF Investigators (2011) Rivaroxaban versus Warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891CrossRefPubMedGoogle Scholar
  7. 7.
    Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L, ARISTOTLE Committees and Investigators (2011) Apixaban versus Warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992CrossRefPubMedGoogle Scholar
  8. 8.
    Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM, ENGAGE AF-TIMI 48 Investigators (2013) Edoxaban versus Warfarin in patients with atrial fibrillation. N Engl J Med 369:2093–2104CrossRefPubMedGoogle Scholar
  9. 9.
    Renda G, Zimarino M, Ricci F, Piccini JP, Ezekowitz MD, Patel MR, Cappato R, Giugliano RP, De Caterina R (2016) Efficacy and safety of non-vitamin K antagonist oral anticoagulants after cardioversion for nonvalvular atrial fibrillation. Am J Med 129:1117–1123.e2CrossRefPubMedGoogle Scholar
  10. 10.
    Renda G, Ricci F, De Caterina R, Non-Vitamin K (2017) Antagonist oral anticoagulants for cardioversion in atrial fibrillation: an updated meta-analysis. Am J Med 130:457–461CrossRefPubMedGoogle Scholar
  11. 11.
    Nagarakanti R, Ezekowitz MD, Oldgren J, Yang S, Chernick M, Aikens TH, Flaker G, Brugada J, Kamensky G, Parekh A, Reilly PA, Yusuf S, Connolly SJ (2011) Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation 123:131–136CrossRefPubMedGoogle Scholar
  12. 12.
    Piccini JP, Stevens SR, Lokhnygina Y, Patel MR, Halperin JL, Singer DE, Hankey GJ, Hacke W, Becker RC, Nessel CC, Mahaffey KW, Fox KA, Califf RM, Breithardt G; ROCKET AF Steering Committee & Investigators (2013) Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial. J Am Coll Cardiol 61:1998–2006CrossRefPubMedGoogle Scholar
  13. 13.
    Plitt A, Ezekowitz MD2, De Caterina R (2016) Nordio F4, Peterson N5, Giugliano RP4; ENGAGE AF-TIMI 48 Investigators. Cardioversion of Atrial Fibrillation in ENGAGE AF-TIMI 48. Clin Cardiol 39:345–346CrossRefPubMedGoogle Scholar
  14. 14.
    Flaker G, Lopes RD, Al-Khatib SM, Hermosillo AG, Hohnloser SH, Tinga B, Zhu J, Mohan P, Garcia D, Bartunek J, Vinereanu D, Husted S, Harjola VP, Rosenqvist M, Alexander JH2, Granger CB, ARISTOTLE Committees and Investigators (2014) Efficacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE trial (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation). J Am Coll Cardiol 63:1082–1087CrossRefPubMedGoogle Scholar
  15. 15.
    Cappato R, Ezekowitz MD, Klein AL, Camm AJ, Ma CS, Le Heuzey JY, Talajic M, Scanavacca M, Vardas PE, Kirchhof P, Hemmrich M, Lanius V, Meng IL, Wildgoose P, van Eickels M, Hohnloser SH, X-VeRT Investigators (2014) Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 35:3346–3355CrossRefPubMedGoogle Scholar
  16. 16.
    Goette A, Merino JL, Ezekowitz MD, Zamoryakhin D, Melino M, Jin J, Mercuri MF, Grosso MA, Fernandez V, Al-Saady N, Pelekh N, Merkely B, Zenin S, Kushnir M, Spinar J, Batushkin V, de Groot JR, Lip GY, ENSURE-AF Investigators (2016) Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial. Lancet 388(10055):1995–2003CrossRefPubMedGoogle Scholar
  17. 17.
  18. 18.
    Khan IA (2003) Atrial stunning: basics and clinical considerations. Int J Cardiol 92:113–128CrossRefPubMedGoogle Scholar
  19. 19.
    Adeniran I, MacIver DH, Garratt CJ, Ye J, Hancox JC, Zhang H (2015) Effects of persistent atrial fibrillation-induced electrical remodeling on atrial electro-mechanics—insights from a 3D model of the human atria. PLoS ONE 10:e0142397CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ammar AS, Elsherbiny I, El-Dosouky II, Abd El Salam K, Abd El Hamid M, Khalil W, Ammar M (2015) Left atrial and left atrial appendage functional recovery after cardioversion in patients with recent atrial fibrillation: Serial echocardiographic study. Cardiol J 22:699–707CrossRefPubMedGoogle Scholar
  21. 21.
    Sparks PB, Jayaprakash S, Mond HG, Vohra JK, Grigg LE, Kalman JM (1999) Left atrial mechanical function after brief duration atrial fibrillation. J Am Coll Cardiol 33:342–349CrossRefPubMedGoogle Scholar
  22. 22.
    Deakin CD, Ambler JJ (2006) Post-shock myocardial stunning: a prospective randomised double-blind comparison of monophasic and biphasic waveforms. Resuscitation 68:329–333CrossRefPubMedGoogle Scholar
  23. 23.
    Wang Y, Bajorek B (2014) New oral anticoagulants in practice: pharmacological and practical considerations. Am J Cardiovasc Drugs 14:175–189CrossRefPubMedGoogle Scholar
  24. 24.
    Piccini JP, Fauchier L (2016) Rhythm control in atrial fibrillation. Lancet 388:829–840CrossRefPubMedGoogle Scholar
  25. 25.
    Halvorsen S, Atar D, Yang H, De Caterina R, Erol C, Garcia D, Granger CB, Hanna M, Held C, Husted S, Hylek EM, Jansky P, Lopes RD, Ruzyllo W, Thomas L, Wallentin L (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 35:1864–1872CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Kato ET, Giugliano RP, Ruff CT, Koretsune Y, Yamashita T, Kiss RG, Nordio F, Murphy SA, Kimura T, Jin J, Lanz H, Mercuri M, Braunwald E, Antman EM (2016) Efficacy and safety of edoxaban in elderly patients with atrial fibrillation in the ENGAGE AF-TIMI 48 Trial. J Am Heart Assoc 5(5):e003432CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Ezekowitz MD, Pollack CV, Sanders P, Halperin JL, Spahr J, Cater N, Petkun W, Breazna A, Kirchhof P, Oldgren J (2016) Apixaban compared with parenteral heparin and/or vitamin K antagonist in patients with nonvalvular atrial fibrillation undergoing cardioversion: Rationale and design of the EMANATE trial. Am Heart J 179:59–68CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical & Surgical SciencesUniversity of FoggiaFoggiaItaly
  2. 2.Cardiology DepartmentSan Paolo HospitalBariItaly
  3. 3.Ospedali Riuniti University HospitalFoggiaItaly
  4. 4.Asklepios Klinik Sankt GeorgHamburgGermany
  5. 5.Santa Maria HospitalGVM Care & ResearchBariItaly

Personalised recommendations