부산대학교 도서관

Summary 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. Author Affiliation: (a) Jessa Ziekenhuis, Faculty of Medicine and Life Sciences at the Hasselt University, Hasselt, Belgium (b) Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (c) Applied Health Research Centre, Li Ka Shing Knowledge Institute of St Michael's Hospital, Department of Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada (d) Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (e) Universite Paris-Diderot, Hopital Bichat, Assistance Publique--Hopitaux de Paris, INSERM U-1148, French Alliance for Cardiovascular Trials, Paris, France (f) National Heart and Lung Institute, Royal Brompton Hospital, Imperial College London, London, UK (g) Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland (h) European Cardiovascular Research Institute, Rotterdam, Netherlands (i) Cork University Hospital, Cork, Ireland (j) Erasmus Medical Center, Rotterdam, Netherlands (k) Cardialysis, Rotterdam, Netherlands (l) Academic Medical Center of Amsterdam, Amsterdam, Netherlands (m) Imeldaziekenhuis, Bonheiden, Belgium (n) UOC Cardiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (o) American Heart of Poland, Center for Cardiovascular Research and Development, Katowice, Poland (p) Azienda Ospedaliera S Maria, Terni, Italy (q) 3rd Department of Medicine, Cardiology and Intensive Care Medicine, Wilhelminenhospital and Sigmund Freud University, Medical Faculty, Vienna, Austria (r) Onze Lieve vrouwe Gasthuis, Amsterdam, Netherlands * Correspondence to: Prof Patrick W Serruys, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, Netherlands (footnote)[Dagger] These authors contributed equally Byline: Pascal Vranckx, MD (a,[Dagger]), Prof Marco Valgimigli, MD (b,[Dagger]), Prof Peter Juni, MD (c,[Dagger]), Prof Christian Hamm, MD (d), Prof Philippe Gabriel Steg, MD (e,f), Dik Heg, PhD (g), Gerrit Anne van Es, PhD (h), Eugene P McFadden, MD (i), Yoshinobu Onuma, MD (j,k), Cokky van Meijeren, PhD (k), Ply Chichareon, MD (l), Edouard Benit, MD (a), Prof Helge Mollmann, MD (d), Luc Janssens, MD (m), Maurizio Ferrario, MD (n), Aris Moschovitis, MD (b), Aleksander Zurakowski, MD (o), Marcello Dominici, MD (p), Prof Robert Jan Van Geuns, MD (j), Prof Kurt Huber, MD (q), Ton Slagboom, MD (r), Prof Patrick W Serruys, MD [patrick.w.j.c.serruys@gmail.com] (j,l,*), Prof Stephan Windecker, MD [stephan.windecker@insel.ch] (b,**), Mohamed Abdellaoui, David Adlam, Ibrahim Akin, Agustin Albarran Gonzalez-Trevilla, Manuel Almeida, Pedro Alves Lemos Neto, Adel Aminian, Richard Anderson, Rick Andreae, Michael Angioi, Taku Asano, Emanuele Barbato, Peter Barlis, Pascal Barraud, Edouard Benit, Olivier Bertrand, Farzin Beygui, Leonardo Bolognese, Roberto Botelho, Coby Bouwman, Marco Bressers, Philippe Brunel, Pawel Buszman, Ian Buysschaert, Pedro Canas da Silva, Didier Carrie, Angel 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, Istvan Edes, Eric Eeckhout, Ingo Eitel, Jozsef Falukozy, Farzin Fath-Ordoubadi, Maurizio Ferrario, Geza Fontos, Jose Francisco Diaz, Edgard Freitas Quintella, Bernhard Frey, Guy Friedrich, Gavin Galasko, Grzegorz Galuszka, Vasco Gama Ribeiro, Scot Garg, Giuseppe Gargiulo, Tobias Geisler, Valeri Gelev, Art Ghandilyan, Javier Goicolea, Tommaso Gori, Felice Gragnano, Ana Guimaraes, Christian Hamm, Michael Haude, Dik Heg, Pieter Heijke, Rosa Ana Hernandez Antolin, David Hildick-Smith, Dorien Hillen, Ina Hoekman, Sjoerd Hofma, Lene Holmvang, Stephen Hoole, Ivan Horvath, Kurt Huber, Annemarie Hugense, Karim Ibrahim, Andres Iniguez, Karl Isaaz, Zoltan Jambrik, Luc Janssens, Pawel Jasionowicz, Judith Jonk, Werner Jung, Peter Juni, Yuki Katagiri, Norihiro Kogame, Tian Hai Koh, Rene Koning, Mariana Konteva, Zsolt Koszegi, Florian Krackhardt, Yvonne Kreuger, Neville Kukreja, Boudijn Ladan, Pierre Lantelme, Sergio Leandro, Gregor Leibundgut, Christoph Liebetrau, Wietze Lindeboom, Carlos Macaya Miguel, Francois Mach, Michael Magro, Luc Maillard, Negar Manavifar, Laura Mauri, Eugene McFadden, Bela Merkely, Yosuke Miyazaki, Adam Mlodziankowski, Tiziano Moccetti, Rodrigo Modolo, Helge Mollman, Jean-Francois Morelle, Aris Moschovitis, Michael Munndt Ottesen, Martin Muurling, Christoph Kurt Naber, Franz-Josef Neumann, Keith Oldroyd, Paul Ong, Yoshinobu Onuma, Sanne Palsrok, Ivo Petrov, Sylvain Plante, Janusz Prokopczuk, Tessa Rademaker-Havinga, Christopher Raffel, Benno Rensing, Marco Roffi, Kees-Jan Royaards, Manel Sabate, Volker Schachinger, Tim Seidler, Antonio Serra Penaranda, Patrick Serruys, Lali Sikarulidze, Ton Slagboom, Osama I Soliman, Amanda Sousa, Ernest Spitzer, Rod Stables, Gabriel Steg, Clemens Steinwender, Eduardas Subkovas, Harry Suryapranata, Kuniaki Takahashi, Suneel Talwar, Emmanuel Teiger, Addy ter Weele, Eva Teurlings, Attila Thury, Jan Tijssen, Gincho Tonev, Diana Trendafilova-Lazarova, Carlo Tumscitz, Victor Umans, Imre Ungi, Veselin Valkov, Pim van der Harst, Robert Jan van Geuns, Cokky van Meijeren, Dobrin Vassilev, Vasil Velchev, Esther Velthuizen, Freek Verheugt, Natalia Vlcek, Jurgen vom Dahl, Mathias Vrolix, Simon Walsh, Nikos Werner, Stephan Windecker, Maarten Witsenburg, Azfar Zaman, Krzysztof Zmudka, Bernhard Zrenner, Aleksander Zurakowski, Robert Zweiker