1. 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
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Pascal Vranckx, Marco Valgimigli, Peter Jüni, Christian Hamm, Philippe Gabriel Steg, Dik Heg, Gerrit Anne van Es, Eugene P McFadden, Yoshinobu Onuma, Cokky van Meijeren, Ply Chichareon, Edouard Benit, Helge Möllmann, Luc Janssens, Maurizio Ferrario, Aris Moschovitis, Aleksander Zurakowski, Marcello Dominici, Robert Jan Van Geuns, Kurt Huber, Ton Slagboom, Patrick W Serruys, Stephan Windecker, 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, 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, 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, István Édes, Eric Eeckhout, Ingo Eitel, József Faluközy, Farzin Fath-Ordoubadi, 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 Guimarães, Michael Haude, Pieter Heijke, Rosa Ana Hernández Antolin, David Hildick-Smith, Dorien Hillen, Ina Hoekman, Sjoerd Hofma, Lene Holmvang, Stephen Hoole, Iván Horváth, Annemarie Hugense, Karim Ibrahim, Andres Iñiguez, Karl Isaaz, Zoltán Jambrik, Pawel Jasionowicz, Judith Jonk, Werner Jung, Yuki Katagiri, Norihiro Kogame, Tian Hai Koh, René Koning, Mariana Konteva, Zsolt Kőszegi, Florian Krackhardt, Yvonne Kreuger, Neville Kukreja, Boudijn Ladan, Pierre Lantelme, Sergio Leandro, Gregor Leibundgut, Christoph Liebetrau, Wietze Lindeboom, Carlos Macaya Miguel, François Mach, Michael Magro, Luc Maillard, Negar Manavifar, Laura Mauri, Eugene McFadden, Bela Merkely, Yosuke Miyazaki, Adam Młodziankowski, Tiziano Moccetti, Rodrigo Modolo, Helge Möllman, Jean-François Morelle, Michael Munndt Ottesen, Martin Muurling, Christoph Kurt Naber, Franz-Josef Neumann, Keith Oldroyd, Paul Ong, Sanne Palsrok, Ivo Petrov, Sylvain Plante, Janusz Prokopczuk, Tessa Rademaker-Havinga, Christopher Raffel, Benno Rensing, Marco Roffi, Kees-Jan Royaards, Manel Sabate, Volker Schächinger, Tim Seidler, Antonio Serra Peñaranda, Patrick Serruys, Lali Sikarulidze, 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, Dobrin Vassilev, Vasil Velchev, Esther Velthuizen, Freek Verheugt, Natalia Vlcek, Jürgen vom Dahl, Mathias Vrolix, Simon Walsh, Nikos Werner, Maarten Witsenburg, Azfar Zaman, Krzysztof Żmudka, Bernhard Zrenner, Robert Zweiker, University of Zurich, Serruys, Patrick W, Cardiology, Vranckx, P., Valgimigli, M., Juni, P., Hamm, C., Steg, P. G., Heg, D., van Es, G. A., Mcfadden, E. P., Onuma, Y., van Meijeren, C., Chichareon, P., Benit, E., Mollmann, H., Janssens, L., Ferrario, M., Moschovitis, A., Zurakowski, A., Dominici, M., Van Geuns, R. J., Huber, K., Slagboom, T., Serruys, P. W., Windecker, S., Abdellaoui, M., Adlam, D., Akin, I., Albarran Gonzalez-Trevilla, A., Almeida, M., Alves Lemos Neto, P., Aminian, A., Anderson, R., Andreae, R., Angioi, M., Asano, T., Barbato, E., Barlis, P., Barraud, P., Bertrand, O., Beygui, F., Bolognese, L., Botelho, R., Bouwman, C., Bressers, M., Brunel, P., Buszman, P., Buysschaert, I., Canas da Silva, P., Carrie, D., Cequier, A., Chin Chang, C., Chowdhary, S., Collet, C., Colombo, A., Cotton, J., Cruz Ferreira, R., Curello, S., Curzen, N., de Bot, J., de Vreede, T., Delle Karth, G., Dijksma, L., Edes, I., Eeckhout, E., Eitel, I., Falukozy, J., Fath-Ordoubadi, F., Fontos, G., Francisco Diaz, J., Freitas Quintella, E., Frey, B., Friedrich, G., Galasko, G., Galuszka, G., Gama Ribeiro, V., Garg, S., Gargiulo, G., Geisler, T., Gelev, V., Ghandilyan, A., Goicolea, J., Gori, T., Gragnano, F., Guimaraes, A., Haude, M., Heijke, P., Hernandez Antolin, R. A., Hildick-Smith, D., Hillen, D., Hoekman, I., Hofma, S., Holmvang, L., Hoole, S., Horvath, I., Hugense, A., Ibrahim, K., Iniguez, A., Isaaz, K., Jambrik, Z., Jasionowicz, P., Jonk, J., Jung, W., Katagiri, Y., Kogame, N., Koh, T. H., Koning, R., Konteva, M., Koszegi, Z., Krackhardt, F., Kreuger, Y., Kukreja, N., Ladan, B., Lantelme, P., Leandro, S., Leibundgut, G., Liebetrau, C., Lindeboom, W., Macaya Miguel, C., Mach, F., Magro, M., Maillard, L., Manavifar, N., Mauri, L., Mcfadden, E., Merkely, B., Miyazaki, Y., Mlodziankowski, A., Moccetti, T., Modolo, R., Mollman, H., Morelle, J. -F., Munndt Ottesen, M., Muurling, M., Naber, C. K., Neumann, F. -J., Oldroyd, K., Ong, P., Palsrok, S., Petrov, I., Plante, S., Prokopczuk, J., Rademaker-Havinga, T., Raffel, C., Rensing, B., Roffi, M., Royaards, K. -J., Sabate, M., Schachinger, V., Seidler, T., Serra Penaranda, A., Serruys, P., Sikarulidze, L., Soliman, O. I., Sousa, A., Spitzer, E., Stables, R., Steg, G., Steinwender, C., Subkovas, E., Suryapranata, H., Takahashi, K., Talwar, S., Teiger, E., ter Weele, A., Teurlings, E., Thury, A., Tijssen, J., Tonev, G., Trendafilova-Lazarova, D., Tumscitz, C., Umans, V., Ungi, I., Valkov, V., van der Harst, P., van Geuns, R. J., Vassilev, D., Velchev, V., Velthuizen, E., Verheugt, F., Vlcek, N., vom Dahl, J., Vrolix, M., Walsh, S., Werner, N., Witsenburg, M., Zaman, A., Zmudka, K., Zrenner, B., Zweiker, R., ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Graduate School, ACS - Heart failure & arrhythmias, and ACS - Amsterdam Cardiovascular Sciences
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medicine.medical_specialty ,Aspirin ,Acute coronary syndrome ,business.industry ,medicine.medical_treatment ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Percutaneous coronary intervention ,610 Medicine & health ,General Medicine ,2700 General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Clopidogrel ,11171 Cardiocentro Ticino ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Drug-eluting stent ,Internal medicine ,medicine ,030212 general & internal medicine ,Myocardial infarction ,business ,Ticagrelor ,medicine.drug - Abstract
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 followup 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. Copright (C) 2018 Elsevier Ltd. All rights reserved. European Clinical Research Institute; Biosensors International; AstraZeneca; Medicines Company; Canada Research Chairs Programme
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- 2018