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房颤消融术中达比加群与华法林不间断抗凝的比较研究
Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation


Hugh Calkins ... 心脑血管疾病 • 2017.04.27
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RE-CIRCUIT述评

 

吴轶喆,葛均波*

复旦大学附属中山医院心内科

*通讯作者

 

心房颤动(房颤)最严重的并发症是由于血栓形成而导致的体循环栓塞(卒中等),是严重危害人群健康的疾病。临床使用华法林抗凝预防房颤卒中有着悠久的历史,效果确切且易于预测。近年来,新型口服抗凝药物(non-vitamin K antagonist oral anti-coagulation,NOAC)也被证实可明显减少卒中和血栓并发症,同时可显著降低出血风险1-3,且不需要像华法林那样频繁检测PT-INR(凝血酶原时间国际标准化比值),在临床上已越来越多地被用于非瓣膜病房颤的抗凝治疗。此外,随着导管消融技术的进步,射频消融已成为部分房颤类型的一线治疗手段。

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摘要


背景

心房颤动导管消融术通常应用华法林不间断抗凝或非维生素K拮抗剂类口服抗凝剂间断性抗凝。应用达比加群等非维生素K拮抗剂类口服抗凝剂进行不间断抗凝可能更加安全,但并无对照数据。该研究调查比较了房颤消融术患者接受达比加群与华法林不间断抗凝的安全性。

 

方法

这项随机、开放标签、多中心、对照试验采用盲法裁定终点评估,研究将计划采用导管消融术治疗阵发性或持续性房颤的患者随机分组,分别接受达比加群(150 mg,每日2次)或华法林(目标国际标准化比值[INR]为2.0~3.0)。不间断抗凝治疗4~8周后行消融术,抗凝治疗在消融术期间持续,消融术后继续治疗8周。该研究主要终点为消融术期间和消融术后8周内严重出血事件的发生率,次要终点包括血栓栓塞性出血事件和其他出血事件。

 

结果

该试验纳入了104个试验中心的704例患者,其中635例患者接受消融治疗。研究对患者的基线特征进行了组间平衡。就消融期间和消融后8周内严重出血事件的发生率而言,达比加群组低于华法林组(5例[1.6%]对22例[6.9%];绝对危险度差异为-5.3个百分点;95%置信区间[CI],-8.4~-2.2;P<0.001)。达比加群组围手术期心脏压塞和腹股沟血肿较华法林组少。两个治疗组轻微出血事件的发生率相似。华法林组有1例血栓栓塞事件。

 

结论

由此可见,接受消融的房颤患者中,达比加群不间断抗凝治疗与华法林不间断抗凝治疗相比,出血并发症更少(该研究由勃林格殷格翰[Boehringer Ingelheim]资助,RE-CIRCUIT在ClinicalTrials.gov注册号为NCT02348723)。





作者信息

Hugh Calkins, M.D., Stephan Willems, M.D., Edward P. Gerstenfeld, M.D., Atul Verma, M.D., Richard Schilling, M.D., Stefan H. Hohnloser, M.D., Ken Okumura, M.D., Ph.D., Harvey Serota, M.D., Matias Nordaby, M.D., Kelly Guiver, M.Sc., Branislav Biss, M.D., Marc A. Brouwer, M.D., Ph.D., and Massimo Grimaldi, M.D., Ph.D., for the RE-CIRCUIT Investigators*
From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology–Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) — all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew’s Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) — both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.). Address reprint requests to Dr. Calkins at Johns Hopkins Medical Institutions, Sheikh Zayed Tower 7125R, 1800 Orleans St., Baltimore, MD, or at hcalkins@jhmi.edu. *A complete list of investigators in the RE-CIRCUIT (Randomized Evaluation of Dabigatran Etexilate Compared to Warfarin in Pulmonary Vein Ablation: Assessment of an Uninterrupted Periprocedural Anticoagulation Strategy) trial is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-2962

2. 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-e76

3. Calkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace 2012;14:528-606

4. 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;129:2638-2644

5. Page SP, Siddiqui MS, Finlay M, et al. Catheter ablation for atrial fibrillation on uninterrupted warfarin: can it be done without echo guidance? J Cardiovasc Electrophysiol 2011;22:265-270

6. Lakkireddy D, Reddy YM, Di Biase L, et al. Feasibility and safety of dabigatran versus warfarin for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. J Am Coll Cardiol 2012;59:1168-1174

7. Kim JS, She F, Jongnarangsin K, et al. Dabigatran vs warfarin for radiofrequency catheter ablation of atrial fibrillation. Heart Rhythm 2013;10:483-489

8. Yamaji H, Murakami T, Hina K, et al. Usefulness of dabigatran etexilate as periprocedural anticoagulation therapy for atrial fibrillation ablation. Clin Drug Investig 2013;33:409-418

9. Kaiser DW, Streur MM, Nagarakanti R, Whalen SP, Ellis CR. Continuous warfarin versus periprocedural dabigatran to reduce stroke and systemic embolism in patients undergoing catheter ablation for atrial fibrillation or left atrial flutter. J Interv Card Electrophysiol 2013;37:241-247

10. Bassiouny M, Saliba W, Rickard J, et al. Use of dabigatran for periprocedural anticoagulation in patients undergoing catheter ablation for atrial fibrillation. Circ Arrhythm Electrophysiol 2013;6:460-466

11. Nin T, Sairaku A, Yoshida Y, et al. A randomized controlled trial of dabigatran versus warfarin for periablation anticoagulation in patients undergoing ablation of atrial fibrillation. Pacing Clin Electrophysiol 2013;36:172-179

12. Stepanyan G, Badhwar N, Lee RJ, et al. Safety of new oral anticoagulants for patients undergoing atrial fibrillation ablation. J Interv Card Electrophysiol 2014;40:33-38

13. Arshad A, Johnson CK, Mittal S, et al. Comparative safety of periablation anticoagulation strategies for atrial fibrillation: data from a large multicenter study. Pacing Clin Electrophysiol 2014;37:665-673

14. 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;49:278-284

15. Nagao T, Inden Y, Shimano M, et al. Feasibility and safety of uninterrupted dabigatran therapy in patients undergoing ablation for atrial fibrillation. Intern Med 2015;54:1167-1173

16. Lakkireddy D, Reddy YM, Di Biase L, et al. 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 2014;63:982-988

17. Maddox W, Kay GN, Yamada T, et al. Dabigatran versus warfarin therapy for uninterrupted oral anticoagulation during atrial fibrillation ablation. J Cardiovasc Electrophysiol 2013;24:861-865

18. Zhao Y, Yang Y, Tang X, Yu X, Zhang L, Xiao H. New oral anticoagulants compared to warfarin for perioperative anticoagulation in patients undergoing atrial fibrillation catheter ablation: a meta-analysis of continuous or interrupted new oral anticoagulants during ablation compared to interrupted or continuous warfarin. J Interv Card Electrophysiol 2017 January 12 (Epub ahead of print)

19. Wu S, Yang YM, Zhu J, et al. Meta-analysis of efficacy and safety of new oral anticoagulants compared with uninterrupted vitamin K antagonists in patients undergoing catheter ablation for atrial fibrillation. Am J Cardiol 2016;117:926-934

20. Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Association practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651

21. Cappato R, Marchlinski FE, Hohnloser SH, et al. Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation. Eur Heart J 2015;36:1805-1811

22. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-1151

23. Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial. Circulation 2011;123:2363-2372

24. Romanelli RJ, Nolting L, Dolginsky M, Kym E, Orrico KB. Dabigatran versus warfarin for atrial fibrillation in real-world clinical practice: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes 2016;9:126-134

25. Larsen TB, Rasmussen LH, Skjøth F, et al. Efficacy and safety of dabigatran etexilate and warfarin in “real-world” patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol 2013;61:2264-2273

26. Graham DJ, Reichman ME, Wernecke M, et al. Stroke, bleeding, and mortality risks in elderly Medicare beneficiaries treated with dabigatran or rivaroxaban for nonvalvular atrial fibrillation. JAMA Intern Med 2016;176:1662-1671

27. Graham DJ, Reichman ME, Wernecke M, et al. Cardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation. Circulation 2015;131:157-164

28. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013;310:2191-2194

29. ICH harmonised tripartite guideline. Guideline for Good Clinical Practice E6(R1) (http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf).

30. Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993;69:236-239

31. Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. . Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005;3:692-694

32. Sardar P, Nairooz R, Chatterjee S, Wetterslev J, Ghosh J, Aronow WS. Meta-analysis of risk of stroke or transient ischemic attack with dabigatran for atrial fibrillation ablation. Am J Cardiol 2014;113:1173-1177

33. Aryal MR, Ukaigwe A, Pandit A, et al. Meta-analysis of efficacy and safety of rivaroxaban compared with warfarin or dabigatran in patients undergoing catheter ablation for atrial fibrillation. Am J Cardiol 2014;114:577-582

34. Larsen TB, Skjøth F, Nielsen PB, Kjældgaard JN, Lip GY. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 2016;353:i3189-i3189

35. Yao X, Abraham NS, Sangaralingham LR, et al. Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc 2016;5:e003725-e003725

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