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经导管主动脉瓣置换术后应用利伐沙班的对照试验
A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement


George D. Dangas ... 心脑血管疾病 • 2020.01.09
相关阅读
• 经导管或外科主动脉瓣置换术的5年结局 • 经导管主动脉瓣置换术后的瓣叶活动度减小

“伽利略的迷思”—— TAVR术后抗血小板,还是抗凝?这是个抗栓问题

 

叶晓峰,朱云鹏,赵强*

上海交通大学医学院附属瑞金医院心外科

*通讯作者

 

通常的抗(血)栓治疗包括抗血小板与抗凝治疗两大类,前者(抗血小板)的常用药物包括阿司匹林/乙酰水杨酸(抑制花生四烯酸AA代谢)、氯吡格雷/替格瑞洛(拮抗二磷酸腺苷ADP/P2Y12受体)、替洛非班(拮抗糖蛋白IIb/IIIa受体)等;而后者(抗凝)的常用药物包括肝素/低分子肝素(主要增强抗凝血酶Ⅲ活性)、华法林(拮抗维生素K)、达比加群(直接抑制凝血酶)、利伐沙班/阿派沙班(直接抑制凝血因子Xa)等。

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摘要


背景

因子Xa直接抑制剂利伐沙班可否预防经导管主动脉瓣置换术(TAVR)后的血栓栓塞事件尚未明确。

 

方法

我们将TAVR成功后无口服抗凝治疗明确适应证的1,644例患者随机分组,分别接受每日10 mg剂量的利伐沙班(前3个月联用每日75~100 mg剂量的阿司匹林)(利伐沙班组)或每日75~100 mg剂量的阿司匹林(前3个月联用每日75 mg剂量的氯吡格雷)(抗血小板组)。主要疗效结局是由死亡或血栓栓塞事件构成的复合结局。主要安全性结局是大出血、导致失能的出血或危及生命的出血。出于安全性考虑,数据和安全监察委员会提前终止了本试验。

 

结果

中位17个月后,利伐沙班组105例患者和抗血小板组78例患者发生了死亡或首次血栓栓塞事件(意向治疗分析)(发生率分别为每100人-年9.8例和7.2例;利伐沙班的风险比,1.35;95%置信区间[CI],1.01~1.81;P=0.04)。两组分别有46例和31例患者发生了大出血、导致失能的出血或危及生命的出血。(意向治疗分析)(每100人-年4.3例和2.8例;风险比,1.50;95% CI,0.95~2.37;P=0.08)。利伐沙班组和抗血小板组分别有64例和38例患者死亡(分别为每100人-年5.8例和3.4例;风险比,1.69;95% CI,1.13~2.53)。

 

结论

在TAVR成功后无口服抗凝治疗明确适应证的患者中,包含每日10 mg剂量利伐沙班的治疗策略与抗血小板策略相比,前者与较高的死亡或血栓栓塞并发症风险相关,并且与较高的出血风险相关(由拜耳和杨森制药资助;GALILEO在ClinicalTrials.gov注册号为NCT02556203)。





作者信息

George D. Dangas, M.D., Ph.D., Jan G.P. Tijssen, Ph.D., Jochen Wöhrle, M.D., Lars Søndergaard, M.D., Martine Gilard, M.D., Helge Möllmann, M.D., Raj R. Makkar, M.D., Howard C. Herrmann, M.D., Gennaro Giustino, M.D., Stephan Baldus, M.D., Ole De Backer, M.D., Ph.D., Ana H.C. Guimarães, Ph.D., Lars Gullestad, M.D., Annapoorna Kini, M.D., Dirk von Lewinski, M.D., Michael Mack, M.D., Raúl Moreno, M.D., Ulrich Schäfer, M.D., Julia Seeger, M.D., Didier Tchétché, M.D., Karen Thomitzek, M.D., Marco Valgimigli, M.D., Ph.D., Pascal Vranckx, M.D., Ph.D., Robert C. Welsh, M.D., Peter Wildgoose, Ph.D., Albert A. Volkl, Pharm.D., Ana Zazula, M.D., Ronald G.M. van Amsterdam, Ph.D., Dip.Phar.Med., Roxana Mehran, M.D., and Stephan Windecker, M.D. for the GALILEO Investigators*
From the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (G.D.D., G.G., A.K., R. Mehran); National and Kapodistrian University of Athens, Athens (G.D.D.); Amsterdam University Medical Centers–University of Amsterdam, Amsterdam (J.G.P.T.), and Cardialysis, Academic Research Organization, Rotterdam (J.G.P.T., A.H.C.G., R.G.M.A.) — both in the Netherlands; the Department of Internal Medicine II, University of Ulm, Ulm (J.W., J.S.), the Department of Internal Medicine I, St. Johannes Hospital Dortmund, Dortmund (H.M.), the Department of Internal Medicine III, Heart Center, University Hospital of Cologne, Cologne (S.B.), the Department of General and Interventional Cardiology, University Hospital Hamburg-Eppendorf, Hamburg (U.S.), and Bayer, Berlin (K.T.) — all in Germany; the Heart Center, Rigshospitalet, University of Copenhagen, Copenhagen (L.S., O.D.B.); La Cavale Blanche University Hospital, Cardiology Department, Brest (M.G.), and Clinique Pasteur, Toulouse (D.T.) — both in France; Smidt Heart Institute, Cedars–Sinai Medical Center, Los Angeles (R.R.M.); the University of Pennsylvania, Philadelphia (H.C.H.); the Department of Cardiology, Oslo University Hospital Rikshospitalet, and the Institute of Clinical Medicine, University of Oslo — all in Oslo (L.G.); the Department of Cardiology, Medical University of Graz, Graz, Austria (D.L.); Baylor Scott and White Health, Temple, TX (M.M.); the Department of Cardiology, University Hospital of La Paz, Hospital La Paz Institute for Health Research, Madrid (R. Moreno); the Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (M.V., S.W.); the Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, and Faculty of Medicine and Life Sciences, University of Hasselt — all in Hasselt, Belgium (P.V.); Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada (R.C.W.); Janssen Pharmaceuticals, Titusville, NJ (P.W., A.A.V.); and Bayer, São Paulo (A.Z.). Address reprint requests to Dr. Windecker at Inselspital, Bern University Hospital, University of Bern, Freiburgstr. 18, Bern 3010, Switzerland, or at stephan.windecker@insel.ch. *A complete list of investigators in the GALILEO trial is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187-2198.

2. Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med 2016;374:1609-1620.

3. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597-1607.

4. Reardon MJ, Van Mieghem NM, Popma JJ, et al. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med 2017;376:1321-1331.

5. Adams DH, Popma JJ, Reardon MJ, et al. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med 2014;370:1790-1798.

6. Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med 2019;380:1695-1705.

7. Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl J Med 2019;380:1706-1715.

8. Hansson NC, Grove EL, Andersen HR, et al. Transcatheter aortic valve thrombosis: incidence, predisposing factors, and clinical implications. J Am Coll Cardiol 2016;68:2059-2069.

9. Chakravarty T, Søndergaard L, Friedman J, et al. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. Lancet 2017;389:2383-2392.

10. Makkar RR, Fontana G, Jilaihawi H, et al. Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. N Engl J Med 2015;373:2015-2024.

11. Puri R, Auffret V, Rodés-Cabau J. Bioprosthetic valve thrombosis. J Am Coll Cardiol 2017;69:2193-2211.

12. Dangas GD, Weitz JI, Giustino G, Makkar R, Mehran R. Prosthetic heart valve thrombosis. J Am Coll Cardiol 2016;68:2670-2689.

13. Jose J, Sulimov DS, El-Mawardy M, et al. Clinical bioprosthetic heart valve thrombosis after transcatheter aortic valve replacement: incidence, characteristics, and treatment outcomes. JACC Cardiovasc Interv 2017;10:686-697.

14. Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 2017;38:2739-2791.

15. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63(22):e57-e185.

16. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-891.

17. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012;366:9-19.

18. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017;377:1319-1330.

19. Windecker S, Tijssen J, Giustino G, et al. Trial design: rivaroxaban for the prevention of major cardiovascular events after transcatheter aortic valve replacement: rationale and design of the GALILEO study. Am Heart J 2017;184:81-87.

20. Kappetein AP, Head SJ, Généreux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. J Am Coll Cardiol 2012;60:1438-1454.

21. De Backer O, Dangas GD, Jilaihawi H, et al. Reduced leaflet motion after transcatheter aortic-valve replacement. N Engl J Med 2020;382:130-139.

22. Van Belle E, Hengstenberg C, Lefevre T, et al. Cerebral embolism during transcatheter aortic valve replacement: the BRAVO-3 MRI study. J Am Coll Cardiol 2016;68:589-599.

23. Dangas GD, Lefèvre T, Kupatt C, et al. Bivalirudin versus heparin anticoagulation in transcatheter aortic valve replacement: the randomized BRAVO-3 trial. J Am Coll Cardiol 2015;66:2860-2868.

24. Dangas GD, Giustino G. Art and science of cerebrovascular event prevention after transcatheter aortic valve replacement. Circ Cardiovasc Interv 2016;9:9-9.

25. Overtchouk P, Guedeney P, Rouanet S, et al. Long-term mortality and early valve dysfunction according to anticoagulation use: the FRANCE TAVI registry. J Am Coll Cardiol 2019;73:13-21.

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