Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR

被引:207
作者
Van Mieghem, Nicolas M. [1 ]
Unverdorben, Martin [2 ]
Hengstenberg, Christian [3 ]
Moellmann, Helge [4 ]
Mehran, Roxana [11 ]
Lopez-Otero, Diego [12 ]
Nombela-Franco, Luis [13 ]
Moreno, Raul [14 ]
Nordbeck, Peter [5 ]
Thiele, Holger [6 ]
Lang, Irene [3 ]
Zamorano, Jose L. [15 ]
Shawl, Fayaz [16 ]
Yamamoto, Masanori [17 ]
Watanabe, Yusuke [18 ]
Hayashida, Kentaro [19 ]
Hambrecht, Rainer [7 ]
Meincke, Felix
Vranckx, Pascal [21 ]
Jin, James [2 ]
Boersma, Eric [1 ]
Rodes-Cabau, Josep [22 ]
Ohlmann, Patrick [23 ]
Capranzano, Piera [24 ,25 ]
Kim, Hyo-Soo [26 ]
Pilgrim, Thomas [27 ]
Anderson, Richard [29 ]
Baber, Usman [31 ]
Duggal, Anil [2 ]
Laeis, Petra [8 ]
Lanz, Hans [8 ]
Chen, Cathy [2 ]
Valgimigli, Marco [28 ]
Veltkamp, Roland [9 ,10 ,30 ]
Saito, Shigeru [20 ]
Dangas, George D. [11 ,32 ]
机构
[1] Erasmus Univ, Dept Cardiol, Thoraxctr, Med Ctr, Rotterdam, Netherlands
[2] Daiichi Sankyo, Basking Ridge, NJ USA
[3] Med Univ, Vienna Gen Hosp, Div Cardiol, Dept Internal Med 2, Vienna, Austria
[4] St Jo hannes Hosp, Dept Internal Med, Dortmund, Germany
[5] Univ Hosp Wurzburg, Dept Internal Med, Wurzburg, Germany
[6] Univ Leipzig, Dept Internal Med Cardiol, Heart Ctr Leipzig, Leipzig, Germany
[7] Bremer Inst Heart & Circulat Res, Klin Links Weser, Bremen, Germany
[8] Asklepios Klin St Georg, Dept Cardiol, Hamburg, Germany
[9] Daiichi Sankyo Europe, Munich, Germany
[10] Alfried Krupp Hosp, Dept Neurol, Essen, Germany
[11] Univ Hosp Heidelberg, Dept Neurol, Heidelberg, Germany
[12] Mt Sinai Hosp, Zena & Michael Wiener Cardio Vasc Inst, New York, NY USA
[13] Hosp Clin Univ Santiago Compostela, Dept Cardiol, Ctr Invest Biomed Red Enfermedades Car, Santiago De Compostela, Spain
[14] Hosp Clin San Carlos, Cardiovasc Inst, Inst Invest Sanitaria San Carlos, Santiago De Compostela, Spain
[15] Univ Hosp Paz, Dept Cardiol, La Paz, Mexico
[16] Univ Hosp Ramon y Cajal, Dept Cardiol, Madrid, Spain
[17] Washington Adventist Hosp, Dept Cardiol, Takoma Pk, Washington, DC USA
[18] Toyohashi Heart Ctr, Dept Cardiol, Toyohashi, Aichi, Japan
[19] Teikyo Univ, Dept Cardiol, Sch Med, Tokyo, Japan
[20] Keio Univ, Dept Cardiol, Sch Med, Tokyo, Japan
[21] Shonan Kamakura Gen Hosp, Div Cardiol & Catheterizat Labs, Kamakura, Kanagawa, Japan
[22] Jessa Hosp, Dept Cardiol, Hasselt, Belgium
[23] Laval Univ, Quebec Heart & Lung Inst, Quebec City, PQ, Canada
[24] Univ Hosp Strasbourg, Div Cardiovasc Med, Strasbourg, France
[25] Univ Catania, Div Cardiol, Policlin Hosp, Catania, Italy
[26] Seoul Natl Univ Hosp, Dept Internal Med, Cardiovasc Ctr, Seoul, South Korea
[27] Univ Bern, Dept Cardiol, Bern, Switzerland
[28] Univ Italian Switzerland, Cardioctr Ticino Inst, Dept Biomed Sci, Lugano, Switzerland
[29] Univ Hosp Wales, Dept Cardiol, Cardiff, Wales
[30] Imperial Coll London, Div Brain Sci, London, England
[31] Univ Oklahoma Hlth Sci Ctr, Cardiol Sect, Oklahoma City, OK USA
[32] Natl & Kapodistrian Univ Athens, Sch Med, Athens, Greece
关键词
AORTIC-VALVE IMPLANTATION; TRANSCATHETER; REPLACEMENT; WARFARIN; STENOSIS;
D O I
10.1056/NEJMoa2111016
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. Methods We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. Results A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P=0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P=0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). Conclusions In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, .) Edoxaban for Atrial Fibrillation with TAVR In a randomized trial involving patients who had atrial fibrillation after TAVR, edoxaban was noninferior to vitamin K antagonists with respect to a composite outcome of death, MI, stroke, thromboembolism, valve thrombosis, or major bleeding but was associated with a higher incidence of major bleeding.
引用
收藏
页码:2150 / 2160
页数:11
相关论文
共 22 条
[1]   Transcatheter Aortic-Valve Replacement with a Self-Expanding Prosthesis [J].
Adams, David H. ;
Popma, Jeffrey J. ;
Reardon, Michael J. ;
Yakubov, Steven J. ;
Coselli, Joseph S. ;
Deeb, G. Michael ;
Gleason, Thomas G. ;
Buchbinder, Maurice ;
Hermiller, James, Jr. ;
Kleiman, Neal S. ;
Chetcuti, Stan ;
Heiser, John ;
Merhi, William ;
Zorn, George ;
Tadros, Peter ;
Robinson, Newell ;
Petrossian, George ;
Hughes, G. Chad ;
Harrison, J. Kevin ;
Conte, John ;
Maini, Brijeshwar ;
Mumtaz, Mubashir ;
Chenoweth, Sharla ;
Oh, Jae K. .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (19) :1790-1798
[2]   Increased prevalence of aortic stenosis in patients with arteriovenous malformations of the gastrointestinal tract in Heyde syndrome [J].
Batur, P ;
Stewart, WJ ;
Isaacson, JH .
ARCHIVES OF INTERNAL MEDICINE, 2003, 163 (15) :1821-1824
[3]   Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation [J].
Brouwer, Jorn ;
Nijenhuis, Vincent J. ;
Delewi, Ronak ;
Hermanides, Renicus S. ;
Holvoet, Wouter ;
Dubois, Christophe L. F. ;
Frambach, Peter ;
De Bruyne, Bernard ;
van Houwelingen, Gert K. ;
Van der Heyden, Jan A. S. ;
Tousek, Petr ;
van der Kley, Frank ;
Buysschaert, Ian ;
Schotborgh, Carl E. ;
Ferdinande, Bert ;
van der Harst, Pim ;
Roosen, John ;
Peper, Joyce ;
Thielen, Frederick W. F. ;
Veenstra, Leo ;
Yin, Dean R. P. P. Chan Pin ;
Swaans, Martin J. ;
Rensing, Benno J. W. M. ;
van 't Hof, Arnoud W. J. ;
Timmers, Leo ;
Kelder, Johannes C. ;
Stella, Pieter R. ;
Baan, Jan ;
ten Berg, Jurrien M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (15) :1447-1457
[4]   Edoxaban for the Prevention of Thromboembolism in Patients With Atrial Fibrillation and Bioprosthetic Valves [J].
Carnicelli, Anthony P. ;
De Caterina, Raffaele ;
Halperin, Jonathan L. ;
Renda, Giulia ;
Ruff, Christian T. ;
Trevisan, Marco ;
Nordio, Francesco ;
Mercuri, Michele F. ;
Antman, Elliott ;
Giugliano, Robert P. .
CIRCULATION, 2017, 135 (13) :1273-1275
[5]   Oral anti-Xa anticoagulation after trans-aortic valve implantation for aortic stenosis: The randomized ATLANTIS trial [J].
Collet, Jean-Philippe ;
Berti, Sergio ;
Cequier, Angel ;
Van Belle, Eric ;
Lefevre, Thierry ;
Leprince, Pascal ;
Neumann, Franz-Josef ;
Vicaut, Eric ;
Montalescot, Gilles .
AMERICAN HEART JOURNAL, 2018, 200 :44-50
[6]   Dabigatran versus Warfarin in Patients with Atrial Fibrillation. [J].
Connolly, Stuart J. ;
Ezekowitz, Michael D. ;
Yusuf, Salim ;
Eikelboom, John ;
Oldgren, Jonas ;
Parekh, Amit ;
Pogue, Janice ;
Reilly, Paul A. ;
Themeles, Ellison ;
Varrone, Jeanne ;
Wang, Susan ;
Alings, Marco ;
Xavier, Denis ;
Zhu, Jun ;
Diaz, Rafael ;
Lewis, Basil S. ;
Darius, Harald ;
Diener, Hans-Christoph ;
Joyner, Campbell D. ;
Wallentin, Lars .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (12) :1139-1151
[7]   A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement [J].
Dangas, George D. ;
Tijssen, Jan G. P. ;
Woehrle, Jochen ;
Sondergaard, Lars ;
Gilard, Martine ;
Moellmann, Helge ;
Makkar, Raj R. ;
Herrmann, Howard C. ;
Giustino, Gennaro ;
Baldus, Stephan ;
De Backer, Ole ;
Guimaraes, Ana H. C. ;
Gullestad, Lars ;
Kini, Annapoorna ;
von Lewinski, Dirk ;
Mack, Michael ;
Moreno, Raul ;
Schaefer, Ulrich ;
Seeger, Julia ;
Tchetche, Didier ;
Thomitzek, Karen ;
Valgimigli, Marco ;
Vranckx, Pascal ;
Welsh, Robert C. ;
Wildgoose, Peter ;
Volkl, Albert A. ;
Zazula, Ana ;
van Amsterdam, Ronald G. M. ;
Mehran, Roxana ;
Windecker, Stephan .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (02) :120-129
[8]   Reduced Leaflet Motion after Transcatheter Aortic-Valve Replacement [J].
De Backer, Ole ;
Dangas, George D. ;
Jilaihawi, Hasan ;
Leipsic, Jonathon A. ;
Terkelsen, Christian J. ;
Makkar, Raj ;
Kini, Annapoorna S. ;
Veien, Karsten T. ;
Abdel-Wahab, Mohamed ;
Kim, Won-Keun ;
Balan, Prakash ;
Van Mieghem, Nicolas ;
Mathiassen, Ole N. ;
Jeger, Raban V. ;
Arnold, Martin ;
Mehran, Roxana ;
Guimaraes, Ana H. C. ;
Norgaard, Bjarne L. ;
Kofoed, Klaus F. ;
Blanke, Philipp ;
Windecker, Stephan ;
Sondergaard, Lars .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (02) :130-139
[9]   Edoxaban versus Warfarin in Patients with Atrial Fibrillation [J].
Giugliano, Robert P. ;
Ruff, Christian T. ;
Braunwald, Eugene ;
Murphy, Sabina A. ;
Wiviott, Stephen D. ;
Halperin, Jonathan L. ;
Waldo, Albert L. ;
Ezekowitz, Michael D. ;
Weitz, Jeffrey I. ;
Spinar, Jindrich ;
Ruzyllo, Witold ;
Ruda, Mikhail ;
Koretsune, Yukihiro ;
Betcher, Joshua ;
Shi, Minggao ;
Grip, Laura T. ;
Patel, Shirali P. ;
Patel, Indravadan ;
Hanyok, James J. ;
Mercuri, Michele ;
Vogelmann, O. ;
Gonzalez, C. ;
Ahuad Guerrero, R. ;
Rodriguez, M. ;
Albisu, J. ;
Rosales, E. ;
Allall, O. ;
Reguero, M. ;
Alvarez, C. ;
Garcia, M. ;
Ameriso, S. ;
Ameriso, P. ;
Amuchastegui, M. ;
Caceres, M. ;
Beloscar, J. ;
Petrucci, J. ;
Berli, M. ;
Budassi, N. ;
Valle, M. ;
Bustamante Labarta, G. ;
Saravia, M. ;
Caccavo, A. ;
Fracaro, V. ;
Cartasegna, L. ;
Novas, V. ;
Caruso, O. ;
Saa Zarandon, R. ;
Colombo, H. ;
Morandini, M. ;
Cuello, J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (22) :2093-2104
[10]   Apixaban versus Warfarin in Patients with Atrial Fibrillation [J].
Granger, Christopher B. ;
Alexander, John H. ;
McMurray, John J. V. ;
Lopes, Renato D. ;
Hylek, Elaine M. ;
Hanna, Michael ;
Al-Khalidi, Hussein R. ;
Ansell, Jack ;
Atar, Dan ;
Avezum, Alvaro ;
Cecilia Bahit, M. ;
Diaz, Rafael ;
Easton, J. Donald ;
Ezekowitz, Justin A. ;
Flaker, Greg ;
Garcia, David ;
Geraldes, Margarida ;
Gersh, Bernard J. ;
Golitsyn, Sergey ;
Goto, Shinya ;
Hermosillo, Antonio G. ;
Hohnloser, Stefan H. ;
Horowitz, John ;
Mohan, Puneet ;
Jansky, Petr ;
Lewis, Basil S. ;
Luis Lopez-Sendon, Jose ;
Pais, Prem ;
Parkhomenko, Alexander ;
Verheugt, Freek W. A. ;
Zhu, Jun ;
Wallentin, Lars .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (11) :981-992