Abstract
Cumulative reports comparing the efficacy and safety outcomes between uninterrupted NOACs and vitamin K antagonists (VKA) in AF ablation had been freshly published. This meta-analysis aimed at offering a more comprehensive evaluation between these two anticoagulants in uninterrupted strategy. We searched in PUBMED, EMBASE, and Cochrane Library (inception to June 10, 2019) for eligible studies. Fixed-effects model was preferred in pooled analysis if I2 < 50%. Publication bias was also evaluated. A total of 23 studies involving 12,725 individuals were analyzed in this literature. There were no difference between uninterrupted NOACs and VKA groups in incidence of Stroke/TIA (RR 0.98, 95% CI 0.54–1.77, P = 0.93, I2 = 0%), silent cerebral embolism (RR 1.09, 95% CI 0.82–1.43, P = 0.56, I2 = 0%), minor bleeding complication (RR 0.97, 95% CI 0.83–1.14, P = 0.73, I2 = 0%), cardiac tamponade (RR 0.95, 95% CI 0.63–1.42, P = 0.80, I2 = 0%). Uninterrupted NOACs was associated with significantly lower major bleeding incidence (RR 0.67, 95% CI 0.49–0.92, P = 0.01, I2 = 0%), pericardial effusion (RR 0.75, 95% CI 0.56–1.00, P = 0.048, I2 = 9%). In sub-analysis, no difference was found in all sub-analyses for Stroke/TIA while significant major bleeding risk reduction in uninterrupted NOACs was identified in the subgroup of CHA2DS2-VASc score ≥ 2 and target activated clotting time (ACT) > 300 s. In conclusions, uninterrupted NOACs was more effective than uninterrupted VKA in reducing major bleeding and pericardial effusion risk without increasing thromboembolism risk, and the benefits of uninterrupted NOACs on major bleeding complication could be more pronounced if CHA2DS2-VASc score ≥ 2 or target ACT > 300 s.
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References
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. https://doi.org/10.1161/CIRCULATIONAHA.113.005119
January CT, Wann LS, Calkins H et al (2019) 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Circulation. https://doi.org/10.1161/CIR.0000000000000665
Di Biase L, Burkhardt JD, Santangeli P et al (2014) 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 129(25):2638–2644. https://doi.org/10.1161/CIRCULATIONAHA.113.006426
Nairooz R, Ayoub K, Sardar P et al (2016) Uninterrupted new oral anticoagulants compared with uninterrupted vitamin K antagonists in ablation of atrial fibrillation: a meta-analysis. Can J Cardiol 32(6):814–823. https://doi.org/10.1016/j.cjca.2015.09.012
Calkins H, Hindricks G, Cappato R et al (2018) 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary. Europace 20(1):157–208. https://doi.org/10.1093/europace/eux275
Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. https://doi.org/10.1136/bmj.b2535
Cappato R, Marchlinski FE, Hohnloser SH et al (2015) Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J 36(28):1805–1811. https://doi.org/10.1093/eurheartj/ehv177
Calkins H, Willems S, Gerstenfeld EP et al (2017) Uninterrupted dabigatran versus warfarin for ablation in atrial fibrillation. N Engl J Med 376(17):1627–1636. https://doi.org/10.1056/NEJMoa1701005
Kirchhof P, Haeusler KG, Blank B et al (2018) Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation. Eur Heart J 39(32):2942–2955. https://doi.org/10.1093/eurheartj/ehy176
Hohnloser SH, Camm J, Cappato R et al (2019) Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial. Eur Heart J. https://doi.org/10.1093/eurheartj/ehz190
Yoshimura A, Iriki Y, Ichiki H et al (2017) Evaluation of safety and efficacy of periprocedural use of rivaroxaban and apixaban in catheter ablation for atrial fibrillation. J Cardiol 69(1):228–235. https://doi.org/10.1016/j.jjcc.2016.03.014
Kuwahara T, Abe M, Yamaki M et al (2016) Apixaban versus warfarin for the prevention of periprocedural cerebral thromboembolism in atrial fibrillation ablation: multicenter prospective randomized study. J Cardiovasc Electrophys 27(5):549–554. https://doi.org/10.1111/jce.12928
Kimura T, Kashimura S, Nishiyama T et al (2018) Asymptomatic cerebral infarction during catheter ablation for atrial fibrillation: comparing uninterrupted rivaroxaban and warfarin (ASCERTAIN). JACC Clin Electrophysiol 4(12):1598–1609. https://doi.org/10.1016/j.jacep.2018.08.003
Di Biase L, Lakkireddy D, Trivedi C et al (2015) Feasibility and safety of uninterrupted periprocedural apixaban administration in patients undergoing radiofrequency catheter ablation for atrial fibrillation: results from a multicenter study. Heart Rhythm 12(6):1162–1168. https://doi.org/10.1016/j.hrthm.2015.02.028
Dillier R, Ammar S, Hessling G et al (2014) Safety of continuous periprocedural rivaroxaban for patients undergoing left atrial catheter ablation procedures. Circ Arrhythm Electrophysiol 7(4):576–582. https://doi.org/10.1161/CIRCEP.114.001586
Kaess BM, Ammar S, Reents T et al (2015) Comparison of safety of left atrial catheter ablation procedures for atrial arrhythmias under continuous anticoagulation with apixaban versus phenprocoumon. Am J Cardiol 115(1):47–51. https://doi.org/10.1016/j.amjcard.2014.10.005
Kottmaier M, Bourier F, Pausch H et al (2018) Safety of uninterrupted periprocedural edoxaban versus phenprocoumon for patients who underwent left atrial catheter ablation procedures. Am J Cardiol 121(4):445–449. https://doi.org/10.1016/j.amjcard.2017.11.015
Lakkireddy D, Reddy YM, Di Biase L et al (2014) Feasibility and safety of uninterrupted rivaroxaban for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. J Am Coll Cardiol 63(10):982–988. https://doi.org/10.1016/j.jacc.2013.11.039
Maddox W, Kay GN, Yamada T et al (2013) Dabigatran versus warfarin therapy for uninterrupted oral anticoagulation during atrial fibrillation ablation. J Cardiovasc Electrophys 24(8):861–865. https://doi.org/10.1111/jce.12143
Nagao T, Inden Y, Yanagisawa S et al (2015) Differences in activated clotting time among uninterrupted anticoagulants during the periprocedural period of atrial fibrillation ablation. Heart rhythm 12(9):1972–1978. https://doi.org/10.1016/j.hrthm.2015.04.016
Reynolds MR, Allison JS, Natale A et al (2018) A prospective randomized trial of apixaban dosing during atrial fibrillation ablation: the AEIOU trial. JACC Clin Electrophysiol 4(5):580–588. https://doi.org/10.1016/j.jacep.2017.11.005
Sawhney V, Shaukat M, Volkova E, Jones N, Providencia R, Honarbakhsh S, Dhillon G, Chow A, Lowe M, Lambiase PD, Dhinoja M, Sporton S, Earley MJ, Schilling RJ, Hunter RJ (2018) Catheter ablation for atrial fibrillation on uninterrupted direct oral anticoagulants: a safe approach. Pacing Clin Electrophysiol. https://doi.org/10.1111/pace.13370
Shah RR, Pillai A, Schafer P et al (2017) Safety and efficacy of uninterrupted apixaban therapy versus warfarin during atrial fibrillation ablation. Am J Cardiol 120(3):404–407. https://doi.org/10.1016/j.amjcard.2017.04.041
Tao S, Otomo K, Ono Y et al (2017) Efficacy and safety of uninterrupted rivaroxaban taken preoperatively for radiofrequency catheter ablation of atrial fibrillation compared to uninterrupted warfarin. J Interv Card Electrophysiol 48(2):167–175. https://doi.org/10.1007/s10840-016-0214-6
Vlachos K, Efremidis M, Bazoukis G et al (2017) Safety and efficacy of DOACs vs acenocoumarol in patients undergoing catheter ablation of atrial fibrillation. Clin Cardiol 40(10):847–852. https://doi.org/10.1002/clc.22734
Kojima T, Fujiu K, Fukuma N et al (2018) Periprocedural complications in patients undergoing catheter ablation of atrial fibrillation without discontinuation of a vitamin K antagonist and direct oral anticoagulants. Circ J 82(6):1552–1557. https://doi.org/10.1253/circj.CJ-17-1114
Brinkmeier-Theofanopoulou M, Tzamalis P, Wehrkamp-Richter S et al (2018) Periprocedural anticoagulation during left atrial ablation: interrupted and uninterrupted vitamin K-antagonists or uninterrupted novel anticoagulants. BMC Cardiovasc Disord 18(1):71. https://doi.org/10.1186/s12872-018-0804-6
Osaka Y, Ono Y, Tao S et al (2019) Feasibility and safety of uninterrupted apixaban in patients undergoing radiofrequency ablation for atrial fibrillation. J Interv Card Electrophysiol. https://doi.org/10.1007/s10840-019-00563-6
Yanagisawa S, Inden Y, Fujii A et al (2018) Renal function and risk of stroke and bleeding in patients undergoing catheter ablation for atrial fibrillation: comparison between uninterrupted direct oral anticoagulants and warfarin administration. Heart Rhythm 15(3):348–354. https://doi.org/10.1016/j.hrthm.2017.10.033
Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the S, Standardization Committee of the International Society on T, Haemostasis (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3(4):692–694. https://doi.org/10.1111/j.1538-7836.2005.01204.x
Lincoff AM, Bittl JA, Harrington RA et al (2003) Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 289(7):853–863
Mehran R, Rao SV, Bhatt DL et al (2011) Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 123(23):2736–2747. https://doi.org/10.1161/CIRCULATIONAHA.110.009449
Deneke T, Jais P, Scaglione M et al (2015) Silent cerebral events/lesions related to atrial fibrillation ablation: a clinical review. J Cardiovasc Electrophys 26(4):455–463. https://doi.org/10.1111/jce.12608
Vermeer SE, Prins ND, den Heijer T et al (2003) Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 348(13):1215–1222. https://doi.org/10.1056/NEJMoa022066
Gaita F, Caponi D, Pianelli M et al (2010) Radiofrequency catheter ablation of atrial fibrillation: a cause of silent thromboembolism? Magnetic resonance imaging assessment of cerebral thromboembolism in patients undergoing ablation of atrial fibrillation. Circulation 122(17):1667–1673. https://doi.org/10.1161/CIRCULATIONAHA.110.937953
Jin M-N, Kim T-H, Kang K-W et al (2019) Atrial fibrillation catheter ablation improves 1-year follow-up cognitive function, especially in patients with impaired cognitive function. Circulation 12(7):e007197. https://doi.org/10.1161/CIRCEP.119.007197
Verma A, Debruyne P, Nardi S et al (2013) Evaluation and reduction of asymptomatic cerebral embolism in ablation of atrial fibrillation, but high prevalence of chronic silent infarction: results of the evaluation of reduction of asymptomatic cerebral embolism trial. Circ Arrhythm Electrophysiol 6(5):835–842. https://doi.org/10.1161/CIRCEP.113.000612
Miyazaki S, Kajiyama T, Yamao K et al (2019) Silent cerebral events/lesions after second-generation cryoballoon ablation: how can we reduce the risk of silent strokes? Heart Rhythm 16(1):41–48. https://doi.org/10.1016/j.hrthm.2018.07.011
Cappato R, Calkins H, Chen SA et al (2011) Delayed cardiac tamponade after radiofrequency catheter ablation of atrial fibrillation: a worldwide report. J Am Coll Cardiol 58(25):2696–2697. https://doi.org/10.1016/j.jacc.2011.09.028
Pisters R, Lane DA, Nieuwlaat R et al (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. https://doi.org/10.1378/chest.10-0134
Roldan V, Marin F, Manzano-Fernandez S et al (2013) The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol 62(23):2199–2204. https://doi.org/10.1016/j.jacc.2013.08.1623
Qamar A, Antman EM, Ruff CT et al (2019) Edoxaban versus warfarin in patients with atrial fibrillation and history of liver disease. J Am Coll Cardiol 74(2):179–189. https://doi.org/10.1016/j.jacc.2019.04.061
Kottmaier M, Bourier F, Semmler V et al (2017) Catheter ablation of left atrial arrhythmias on uninterrupted oral anticoagulation with vitamin K antagonists: What is the relationship between international normalized ratio, activated clotting time, and procedure-related complications? J Cardiovasc Electrophys 28(12):1415–1422. https://doi.org/10.1111/jce.13314
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Liu, XH., Gao, XF., Chen, CF. et al. Thromboembolism and bleeding risk in atrial fibrillation ablation with uninterrupted anticoagulation between new oral anticoagulants and vitamin K antagonists: insights from an updated meta-analysis. J Thromb Thrombolysis 50, 201–210 (2020). https://doi.org/10.1007/s11239-019-01989-5
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DOI: https://doi.org/10.1007/s11239-019-01989-5