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Meta-analysis of efficacy and safety of apixaban and uninterrupted apixaban therapy compared to vitamin K antagonists in patients undergoing catheter ablation for atrial fibrillation

  • Anene Ukaigwe
  • Pragya Shrestha
  • Paras Karmacharya
  • Sarah K. Hussain
  • Soraya Samii
  • Mario D. Gonzalez
  • Deborah Wolbrette
  • Gerald V. Naccarrelli
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Abstract

Background

Apixaban is a Factor Xa inhibitor increasingly being used for stroke prevention in atrial fibrillation (AF). Although several studies have been done, the efficacy and safety of apixaban during the peri-procedural period of AF ablation remains unclear. We sought to systematically review pooled data from these various studies to evaluate thromboembolic and bleeding risks in patients undergoing catheter ablation for AF who are treated with apixaban (interrupted and uninterrupted).

Methods

Studies comparing anticoagulation with apixaban or vitamin K antagonists (VKA) in patients undergoing ablation for AF were identified via an electronic search of MEDLINE, EMBASE, clinical trials.gov, and Cochrane Library from inception to January 2016. Study-specific risk ratios were calculated and combined with a fixed-effects model meta-analysis.

Results

In the analysis of 2100 pooled patients, thromboembolic complications (TE) occurred in 14/778 (1.80 %) patients in the apixaban group (AG) compared to 20/1322 patients in the VKA group (RR 1.03, 95 % CI 0.55–1.90, p = 0.93, I 2 = 0 %). Major bleeding occurred in 9/778 (1.2 %) of the AG compared to 20/1322 (1.51 %) in the VKA group (RR 1.03, 95 % CI 0.55–1.90, p = 0.93, I 2 = 0 %). In uninterrupted apixaban group (uAG), TE occurred in 4/585 (0.68 %) patients in the uAG compared to 6/910 (0.66 %) in VKA group (RR 0.86, 95 % CI 0.25–2.95, p = 0.81, I 2 = 0 %). Major bleeding occurred in 5/585 (0.85 %) in uAG compared to 7/910 (0.77 %) in the VKA group (RR 1.20, 95 % CI 0.37–3.88, p = 0.76, I 2 = 0 %).

Conclusion

Our study demonstrates patients treated with apixaban and VKA during the peri-procedural period for AF ablation have similar rates of TE and bleeding complications. Interrupted and uninterrupted apixaban strategies were associated with similar outcomes.

Keywords

Apixaban Atrial fibrillation Catheter ablation 

Notes

Author contributions

Authors AU, PS, and PK conceived, designed, and participated in the abstraction, analysis, interpretation, and drafting of the initial manuscript. Authors SH, MG, GV, SS, and DW analyzed, interpreted, and provided intellectual content, edited the subsequent draft, and approved the final manuscript.

Compliance with ethical standards

Conflicts of interest

Anene Ukaigwe, MD—None.

Pragya Shrestha, MD—None.

Paras Karmacharya, MD—None.

Sarah K. Hussain, MD—Consulting, Speaking Honoraria, Biosense Webster and Speaking Honoraria, Medtronic.

Soraya Samii, MD—None.

Mario D. Gonzalez, MD—Consulting, Speaking Honoraria, Biosense Webster and Biosense Janssen.

Deborah Wolbrette, MD—None.

Gerald V. Naccarelli, MD—Consulting, Glaxo-Smith-Kline, Pfizer, Sanofi, Boehringer-Ingelheim, Bristol Myers Squibb, Otsuka, Janssen, Daiichi-Sankyo, Xention, Astra-Zeneca.

Financial disclosures

None.

Funding

None.

Supplementary material

10840_2016_195_MOESM1_ESM.docx (12 kb)
Supplementary File 1 Search strategy. (DOCX 12 kb)
10840_2016_195_Fig5_ESM.gif (8 kb)
Supplementary File 2

Funnel plots. (GIF 8 kb)

10840_2016_195_MOESM2_ESM.tif (28 kb)
High resolution image (TIF 27 kb)
10840_2016_195_Fig6_ESM.gif (7 kb)
Supplementary File 3

Forest plots demonstrating single cerebral ischemia as sole outcome in patients undergoing AF ablation. (GIF 6 kb)

10840_2016_195_MOESM3_ESM.tif (21 kb)
High resolution image (TIF 21 kb)

References

  1. 1.
    Go AS, Mozaffarian D, Roger VL, et al. Executive summary: heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation. 2014;129:399–410.CrossRefPubMedGoogle Scholar
  2. 2.
    Yamaji H, Murakami T, Hina K, et al. Usefulness of dabigatran etexilate as periprocedural anticoagulation therapy for atrial fibrillation ablation. Clin Drug Investig. 2013;33:409–18.CrossRefPubMedGoogle Scholar
  3. 3.
    Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98:946–52.CrossRefPubMedGoogle Scholar
  4. 4.
    January CT, Wann LS, Alpert JS, et al. 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 Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64:e1–76.CrossRefPubMedGoogle Scholar
  5. 5.
    Di Biase L, Burkhardt JD, Santangeli P, et al. Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: results from the role of coumadin in preventing thromboembolism in atrial fibrillation (AF) patients undergoing catheter ablation (COMPARE) randomized trial. Circulation. 2014;129:2638–44.CrossRefPubMedGoogle Scholar
  6. 6.
    Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.CrossRefPubMedGoogle Scholar
  7. 7.
    Amin A, Bruno A, Trocio J, Lin J, Lingohr-Smith M. Comparison of differences in medical costs when new oral anticoagulants are used for the treatment of patients with non-valvular atrial fibrillation and venous thromboembolism vs warfarin or placebo in the US. J Med Econ. 2015;18:399–409.CrossRefPubMedGoogle Scholar
  8. 8.
    Bin Abdulhak AA, Kennedy KF, Gupta S, Giocondo M, Ramza B, Wimmer AP. Effect of pre-procedural interrupted apixaban on heparin anticoagulation during catheter ablation for atrial fibrillation: a prospective observational study. J Interv Card Electrophysiol. 2015;44:91–6. Int J Arrhythm Pacing.CrossRefPubMedGoogle Scholar
  9. 9.
    Nagao T, Inden Y, Yanagisawa S, et al. Differences in activated clotting time among uninterrupted anticoagulants during the periprocedural period of atrial fibrillation ablation. Heart Rhythm Off J Heart Rhythm Soc. 2015;12:1972–8.CrossRefGoogle Scholar
  10. 10.
    Beller EM, Glasziou PP, Altman DG, et al. PRISMA for Abstracts: reporting systematic reviews in journal and conference abstracts. PLoS Med. 2013;10:e1001419.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Kuwahara T, Abe M, Yamaki M, et al. Apixaban versus warfarin for the prevention of periprocedural cerebral thromboembolism in atrial fibrillation ablation: multicenter prospective randomized study. J Cardiovasc Electrophysiol. 2016.Google Scholar
  12. 12.
    Iriki Y. Evaluation of safety and efficacy of perioperative use of rivaroxaban and apixaban in catheter ablation for atrial fibrillation. Eur Heart J. 2015;36 suppl 1:687.Google Scholar
  13. 13.
    Armbruster HL, Lindsley JP, Moranville MP, et al. Safety of novel oral anticoagulants compared with uninterrupted warfarin for catheter ablation of atrial fibrillation. Ann Pharmacother. 2015;49:278–84.CrossRefPubMedGoogle Scholar
  14. 14.
    Di Biase L, Lakkireddy D, Trivedi C, et al. Feasibility and safety of uninterrupted periprocedural apixaban administration in patients undergoing radiofrequency catheter ablation for atrial fibrillation: results from a multicenter study. Heart Rhythm Off J Heart Rhythm Soc. 2015;12:1162–8.CrossRefGoogle Scholar
  15. 15.
    Kaess BM, Ammar S, Reents T, et al. Comparison of safety of left atrial catheter ablation procedures for atrial arrhythmias under continuous anticoagulation with apixaban versus phenprocoumon. Am J Cardiol. 2015;115:47–51.CrossRefPubMedGoogle Scholar
  16. 16.
    Nagao T, Inden Y, Shimano M, et al. Efficacy and safety of apixaban in the patients undergoing the ablation of atrial fibrillation. Pacing Clin Electrophysiol. 2015;38:155–63. PACE.CrossRefPubMedGoogle Scholar
  17. 17.
    Nilsson KR. Apixaban is a safe alternative to uninterrupted warfarin during catheter ablation of atrial fibrillation. Europace. 2015;17:iii141.Google Scholar
  18. 18.
    Osaka Y. Uninterrupted use of ribaroxaban and apixaban for radiofrequency catheter ablation of atrial fibrillation: comparison with warfarin. Heart Rhythm. 2015;12:S469.Google Scholar
  19. 19.
    Anon. Ottawa Hospital Research Institute. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 1 Feb 2016.
  20. 20.
    Verhagen AP, de Vet HC, de Bie RA, et al. The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol. 1998;51:1235–41.CrossRefPubMedGoogle Scholar
  21. 21.
    Yoshimura A, Iriki Y, Ichiki H, et al. Evaluation of safety and efficacy of periprocedural use of rivaroxaban and apixaban in catheter ablation for atrial fibrillation. J Cardiol. 2016.Google Scholar
  22. 22.
    Anon. Cochrane Handbook for Systematic Reviews of Interventions. Available at: http://handbook.cochrane.org/. Accessed 1 Feb 2016.
  23. 23.
    Rillig A, Lin T, Plesman J, et al. Apixaban, rivaroxaban, and dabigatran in patients undergoing atrial fibrillation ablation. J Cardiovasc Electrophysiol. 2016;27:147–53.CrossRefPubMedGoogle Scholar
  24. 24.
    Camm AJ, Lip GYH, De Caterina R, et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation—developed with the special contribution of the European Heart Rhythm Association. Eur Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol. 2012;14:1385–413.Google Scholar
  25. 25.
    Sticherling C, Marin F, Birnie D, et al. Antithrombotic management in patients undergoing electrophysiological procedures: a European Heart Rhythm Association (EHRA) position document endorsed by the ESC Working Group Thrombosis, Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society (APHRS). Eur Eur Pacing Arrhythm Card Electrophysiol J Work Groups Card Pacing Arrhythm Card Cell Electrophysiol Eur Soc Cardiol. 2015;17:1197–214.Google Scholar
  26. 26.
    Nairooz R, Ayoub K, Sardar P, et al. Uninterrupted new oral anticoagulants compared with uninterrupted vitamin K antagonists in ablation of atrial fibrillation: a meta-analysis. Can J Cardiol. 2015.Google Scholar
  27. 27.
    Lu D, Liu Q, Wang K, Zhang QI, Shan Q-J. Meta-analysis of efficacy and safety of apixaban in patients undergoing catheter ablation for atrial fibrillation. Pacing Clin Electrophysiol. 2016;39:54–9. PACE.CrossRefPubMedGoogle Scholar
  28. 28.
    Garg J, Chaudhary R, Krishnamoorthy P, Shah N, Bozorgnia B. Safety of uninterrupted periprocedural apixaban in patients undergoing atrial fibrillation catheter ablation: a meta-analysis of 1,057 patients. J Am Coll Cardiol. 2016;67:732.CrossRefGoogle Scholar
  29. 29.
    Mani H, Lindhoff-Last E. New oral anticoagulants in patients with nonvalvular atrial fibrillation: a review of pharmacokinetics, safety, efficacy, quality of life, and cost effectiveness. Drug Des Devel Ther. 2014;8:789–98.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Cappato R, Calkins H, Chen S-A, et al. Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation. 2005;111:1100–5.CrossRefPubMedGoogle Scholar
  31. 31.
    Naccarelli GV, Gonzalez MD. Catheter ablation of atrial fibrillation: the need for studies to assess the efficacy and safety of novel anticoagulants. J Interv Card Electrophysiol. 2013;36:3–4. Int J Arrhythm Pacing.CrossRefPubMedGoogle Scholar
  32. 32.
    Lee SI, Sayers M, Lip GYH, Lane DA. Use of non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients: insights from a specialist atrial fibrillation clinic. Int J Clin Pract. 2015;69:1341–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Anon. Apixaban during atrial fibrillation catheter ablation: comparison to vitamin K antagonist therapy—full text view—ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT02227550?term=apixaban+and+atrial+fibrillation&rank=2. Accessed 1 Feb 2016.
  34. 34.
    Anon. Apixaban evaluation of interrupted or uninterrupted anticoagulation for ablation of atrial fibrillation—full text view—ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT02608099?term=apixaban+and+atrial+fibrillation&rank=1. Accessed 1 Feb 2016.

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Anene Ukaigwe
    • 1
  • Pragya Shrestha
    • 2
  • Paras Karmacharya
    • 2
  • Sarah K. Hussain
    • 3
  • Soraya Samii
    • 3
  • Mario D. Gonzalez
    • 3
  • Deborah Wolbrette
    • 3
  • Gerald V. Naccarrelli
    • 3
  1. 1.Division of Cardiology, Heart and Vascular InstitutePennsylvania State University, Hershey Medical CenterHersheyUSA
  2. 2.Department of Medicine, Reading Health SystemWest ReadingUSA
  3. 3.Electrophysiology Program, Division of Cardiology, Heart and Vascular InstitutePenn State University, Hershey Medical CenterHersheyUSA

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