Non-vitamin K antagonist oral anticoagulants in the cardioversion of patients with atrial fibrillation: systematic review and meta-analysis
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Non-vitamin K antagonist oral anticoagulants (NOACs) are at least non-inferior to Vitamin K Antagonists (VKAs) for stroke prevention on patients with non-valvular atrial fibrillation (AF). We aimed to evaluate the efficacy and safety of NOACs in patients undergoing cardioversion through a systematic review and meta-analysis.
MEDLINE, Cochrane Library, and Web of Science® databases (until September 2014) were searched for studies fulfilling inclusion criteria. Two reviewers independently selected randomized controlled trials (RCTs) evaluating NOACs and VKA in patients with AF undergoing cardioversion. The primary outcome was ischemic stroke or systemic embolism (IS/SE). Secondary outcomes were major bleeding, myocardial infarction, and mortality. Risk ratio (RR) and 95 % confidence intervals were derived through random-effects meta-analysis. Heterogeneity was evaluated through I 2 test.
Four RCTs (3 post-hoc analysis) evaluating apixaban, dabigatran, and rivaroxaban in 3,512 patients with AF were included. The risk of IS/SE with NOACs was similar to VKA (RR 0.60, 95 % CI 0.20–1.80; I 2 = 17 %). There was no significant increase in major bleeding (RR 1.27, 95 % CI 0.58–2.81; I 2 = 0 %), myocardial infarction (RR 0.71, 95 % CI 0.10–5.04; I 2 = 0 %), or mortality (RR 0.87, 95 % CI 0.24–3.08; I 2 = 0 %) with NOACs.
This systematic review and meta-analysis suggests that NOACs may be as safe as VKAs in the setting of AF cardioversion.
KeywordsMeta-analysis Electric countershock Stroke Anticoagulants Cardioversion Transesophageal echocardiography
We thank the Portuguese Collaborating Center of the Iberoamerican Cochrane Network. This was an academic project not funded by any government or non-government grant.
Conflict of interest
DC, and JC do not have any competing interests to disclose. JJF had speaker and consultant fees with GlaxoSmithKline, Novartis, TEVA, Lundbeck, Solvay, Abbott, Bial, Merck-Serono, Grunenthal, and Merck Sharp and Dohme. GYHL had consultant fees from Bayer, Astellas, Merck, Astra Zeneca, Sanofi, BMS/Pfizer, Biotronik, Portola, and Boehringer Ingelheim; and has been on the speakers bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim, and Sanofi-Aventis. FJP had consultant and speaker fees with Astra Zeneca, Bayer, and Boehringer Ingelheim.
- 1.Wokhlu A, Monahan KH, Hodge DO, Asirvatham SJ, Friedman PA, Munger TM, Bradley DJ, Bluhm CM, Haroldson JM, Packer DL (2010) Long-term quality of life after ablation of atrial fibrillation the impact of recurrence, symptom relief, and placebo effect. J Am Coll Cardiol 55:2308–2316PubMedCrossRefGoogle Scholar
- 3.Klein AL, Grimm RA, Murray RD, Apperson-Hansen C, Asinger RW, Black IW, Davidoff R, Erbel R, Halperin JL, Orsinelli DA, Porter TR, Stoddard MF, Assessment of Cardioversion Using Transesophageal Echocardiography Investigators (2001) Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 344:1411–1420Google Scholar
- 5.De Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H, Bachmann F, Baigent C, Huber K, Jespersen J, Kristensen SD, Lip GY, Morais J, Rasmussen LH, Siegbahn A, Verheugt FW, Weitz JI, European Society of Cardiology Working Group on Thrombosis Task Force on Anticoagulants in Heart Disease (2013) General mechanisms of coagulation and targets of anticoagulants (section I). Position Paper of the ESC working group on thrombosis-task force on anticoagulants in heart disease. Thromb Haemost 109:569–579Google Scholar
- 7.Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM (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 383:955–962PubMedCrossRefGoogle Scholar
- 10.Nielsen PB, Lane DA, Rasmussen LH, Lip GY, Larsen TB (2014) Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients: a systemic review and meta-regression analysis. Clin Res Cardiol. doi: 10.1007/s00392-014-0797-9 PubMedGoogle Scholar
- 11.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. doi: 10.1136/bmj.b2700 PubMedCentralPubMedCrossRefGoogle Scholar
- 12.Higgins JPT, Altman DG, Sterne JAC. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (eds) Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. www.cochrane-handbook.org. Accessed in Sep 2014
- 15.Deeks JJ, Altman DG, Bradburn MJ (2001) Statistical methods for examining heterogeneity and combining results from several studies in metaanalysis. In Egger M, Davey Smith G, Altman DG (eds) Systematic reviews in health care: meta-analysis in context, 2nd edn. BMJ Publication Group, London, pp 313–335Google Scholar
- 18.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 123:131–136PubMedCrossRefGoogle Scholar
- 19.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, ROCKETAF 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 61:1998–2006PubMedCrossRefGoogle Scholar
- 20.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 JH, Granger CB, ARISTOTLE Committees 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 63:1082–1087PubMedCrossRefGoogle Scholar
- 21.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, on behalf of the X-VeRT Investigators (2014) Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J. doi: 10.1093/eurheartj/ehu367 PubMedGoogle Scholar
- 23.Deeks JJ, Higgins JPT, Altman DG (2011) Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (eds) Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. www.cochrane-handbook.org. Accessed in Sep 2014
- 24.Higgins JPT, Deeks JJ, Altman DG (2011) Chapter 16: Special topics in statistics. In: Higgins JPT, Green S (eds), Cochrane Handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. www.cochrane-handbook.org. Accessed in Sep 2014
- 25.Sterne JAC, Egger M, Moher D (2011) Chapter 10: Addressing reporting biases. In: Higgins JPT, Green S (eds) Cochrane Handbook for systematic reviews of intervention. Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. www.cochrane-handbook.org. Accessed in Sep 2014
- 27.European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH; ESC Committee for Practice Guidelines (2010) Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace. 12:1360–1420Google Scholar
- 32.Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, European Heart Rhythm Association (2013) European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 15:625–651PubMedCrossRefGoogle Scholar
- 37.Edoxaban vs. Warfarin in subjects undergoing cardioversion of atrial fibrillation (ENSURE-AF). ClinicalTrials.gov Identifier: NCT02072434. http://clinicaltrials.gov/show/NCT02072434. Accessed in Sep 2014
- 38.Study of the blood thinner, apixaban, for patients who have an abnormal heart rhythm (atrial fibrillation) and expected to have treatment to put them back into a normal heart rhythm (cardioversion) (EMANATE). ClinicalTrials.gov Identifier: NCT02100228. http://clinicaltrials.gov/show/NCT02100228. Accessed in Sep 2014