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Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial

2018; Elsevier BV; Volume: 392; Issue: 10151 Linguagem: Inglês

10.1016/s0140-6736(18)31858-0

1474-547X

Pascal Vranckx, Marco Valgimigli, Peter Jüni, Christian W. Hamm, Philippe Gabríel Steg, Dik Heg, Gerrit Anne van Es, Eugène McFadden, Yoshinobu Onuma, Cokky van Meijeren, Ply Chichareon, Edouard Benit, Helge Möllmann, Luc Janssens, Maurizio Ferrario, Aris Moschovitis, Aleksander Żurakowski, Marcello Dominici, Robert‐Jan van Geuns, Kurt Huber, Ton Slagboom, Patrick W. Serruys, Stephan Windecker, Mohamed Abdellaoui, David Adlam, İbrahim Akın, Agustín Albarrán González-Trevilla, Manuel Almeida, Pedro A. Lemos, Adel Aminian, Richard Anderson, Rick Andreae, Michaël Angioı̈, Taku Asano, Emanuele Barbato, Peter Barlis, Pascal Barraud, Edouard Benit, Olivier F. Bertrand, Farzin Beygui, Leonardo Bolognese, Roberto Botelho, Coby Bouwman, Marco Bressers, Philippe Brunel, Paweł Buszman, Ian Buysschaert, Pedro Canas da Silva, Didier Carrié, Ángel Cequier, Ply Chichareon, Chun Chin Chang, Saqib Chowdhary, Carlos Collet, Antonio Colombo, James Cotton, Rui Cruz Ferreira, Salvatore Curello, Nick Curzen, Judith de Bot, Tone de Vreede, Georg Delle Karth, Lynn Dijksma, Marcello Dominici, István Édes, Éric Eeckhout, Ingo Eitel, József Faluközy, Farzin Fath‐Ordoubadi, Maurizio Ferrario, Géza Fontos, José Francisco Díaz Fernández, Edgard Freitas Quintella, Bernhard Frey, Guy Friedrich, Gavin Galasko, G. Gałuszka, Vasco Gama Ribeiro, Scot Garg, Giuseppe Gargiulo, Tobias Geisler, Валери Гелев, Art Ghandilyan, Javier Goicolea, Tommaso Gori, Felice Gragnano, Ana Guimarães, Christian W. Hamm, Michael Haude, Dik Heg, Pieter Heijke, Rosa Ana Hernández Antolín, David Hildick‐Smith, Dorien Hillen, Ina Hoekman, Sjoerd H. Hofma, Lene Holmvang, Stephen P. Hoole, Iván Horváth, Kurt Huber, Annemarie Hugense, Karim Ibrahim, Andrés Íñiguez, Karl Isaaz, Zoltán Jambrik, Luc Janssens, Pawel Jasionowicz, Judith Jonk, Werner Jung, Peter Jüni, Yuki Katagiri, Norihiro Kogame, Tian Hai Koh, René Köning, Mariana Konteva, Zsolt Kõszegi, Florian Krackhardt, Yvonne Kreuger, Neville Kukreja, Boudijn Ladan, Pierre Lantelme, Sergio Martins Leandro, Gregor Leibundgut, Christoph Liebetrau, Wietze Lindeboom, Carlos Macaya Miguel, François Mach, Michael Magro, Luc Maillard, Negar Manavifar, Laura Mauri, Eugène McFadden, Béla Merkely, Yosuke Miyazaki, Adam Młodziankowski, Tiziano Moccetti, Rodrigo Modolo, Helge Möllman, Jean‐François Morelle, Aris Moschovitis, Michael Munndt Ottesen, Martin Muurling, Christoph Naber, Franz‐Josef Neumann, Keith G. Oldroyd, Paul Jau Lueng Ong, Yoshinobu Onuma, Sanne Palsrok, Ivo Petrov, Sylvain Planté, Janusz Prokopczuk, Tessa Rademaker‐Havinga, C. Raffel, Benno Rensing, Marco Roffi, Kees‐Jan Royaards, Manel Sabaté, Volker Schächinger, Tim Seidler, Antonio Serra Peñaranda, Patrick W. Serruys, Lali Sikarulidze, Ton Slagboom, Osama Soliman, Amanda Sousa, Ernest Spitzer, Rod Stables, Philippe Gabríel Steg, Clemens Steinwender, Eduardas Subkovas, Harry Suryapranata, Kuniaki Takahashi, Suneel Talwar, Emmanuel Teíger, Addy ter Weele, Eva Teurlings, Attila Thury, Jan G.P. Tijssen, Gincho Tonev, Diana Trendafilova‐Lazarova, Carlo Tumscitz, Victor A. Umans, Imre Ungi, Veselin Valkov, Pim van der Harst, Robert‐Jan van Geuns, Cokky van Meijeren, Dobrin Vassilev, Vasil Velchev, Esther Velthuizen, Freek W.A. Verheugt, Natalia Vlcek, Jürgen vom Dahl, Mathias Vrolix, Simon Walsh, Nikos Werner, Stephan Windecker, Maarten Witsenburg, Azfar Zaman, Krzysztof Żmudka, Bernhard Zrenner, Aleksander Żurakowski, Robert Zweiker,

Acute Myocardial Infarction Research

Background We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75–100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75–100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. Findings Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75–1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78–1·20]; p=0·77). Interpretation Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Funding AstraZeneca, Biosensors, and The Medicines Company.