Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes
Gilles Montalescot, Leonardo Bolognese, Dariusz Dudek, Patrick Goldstein, Christian Hamm, Jean-Francois Tanguay, Jurrien M ten Berg, Debra L Miller, Timothy M Costigan, Jochen Goedicke, Johanne Silvain, Paolo Angioli, Jacek Legutko, Margit Niethammer, Zuzana Motovska, Joseph A Jakubowski, Guillaume Cayla, Luigi Oltrona Visconti, Eric Vicaut, Petr Widimsky, ACCOAST Investigators, Gilles Montalescot, Leonardo Bolognese, Dariusz Dudek, Patrick Goldstein, Christian Hamm, Jean-Francois Tanguay, Jur ten Berg, Petr Widimsky, Marcus Flather, Alfredo Bardají, Andreas Baumbach, Miles Dalby, Akhil Kapur, François Philippe, Pierre Sabouret, Ad F van den Heuvel, Azfar Zaman, Michel Bertrand, Carlo Di Mario, Eric Vicaut, Johann Auer, Giorgio Giacomini, Kurt Huber, Franz Leisch, Thomas Neunteufl, Franz Weidinger, Christophe Beauloye, Patrick Coussement, Walter Desmet, Luc Janssens, Jacques Lalmand, Erwin Schroeder, Mathias Vrolix, Asim N Cheema, Anthony Fung, William Kostuk, Krishnan Ramanathan, Stephane Rinfret, Erick Schampaert, Jeffery Stein, Jean-Francois Tanguay, Mouhiedden Traboulsi, Ivan Hornacek, Milan Hromadka, Jozef Jakabcin, Petr Kala, Jiri Kettner, Jean-Claude Lubanda, Zuzana Motovska, Pavel Sedlon, Roman Stipal, Jan Vojacek, Juhani Airaksinen, Mika Laine, Jean Auffray, Loic Belle, Ziad Boueri, Hervé Le Breton, Pierre Carli, Guillaume Cayla, Nicolas Delarche, Axel de Labriolle, P Ecollan, Simon Elhadad, Emmanuelle Filippi, Bruno Farah, Patrick Goldstein, Pascal Goube, K Khalife, Gilles Montalescot, Jean Mouret, Laurent Payot, Carlos El Khoury, Gregoire Range, Louis Soulat, Olivier Varenne, Karl-Friedrich Appel, Martin Bergmann, Enno Boudriot, Johannes Brachmann, Gudrun Dannberg, Martin Desaga, Henning Ebelt, Evangelos Giannitsis, Rainer Gradaus, Christian Hamm, Franz Hartmann, Werner Jung, Helmut Keller, Peter Meyer, Andreas Mügge, Margit Niethammer, Christoph A Nienaber, Gert Richardt, Andreas Schäfer, Hae-Young Sohn, Nikos Werner, Andreas Zeiher, Uwe Zeymer, Peter Andreka, David Becker, Kalman Csapo, Gyorgy Fogarassy, Ivan G Horvath, Geza Lupkovics, Shaul Atar, Ariel Finkelstein, Yonathan Hasin, Basil S Lewis, Morris Mosseri, Arthur Pollak, Zvi Vered, Toni Badia, Sergio Berti, Leonardo Bolognese, Francesco Maria Bovenzi, Paola Camisasca, Claudio Cavallini, Raffaele De Caterina, Stefano De Servi, Giuseppe Fantini, Claudio Fresco, Antonio Manari, Sebastiano Marra, Ciro Mauro, Luca Olivotti, Anna Sonia Petronio, Francesco Prati, Bernhard Reimers, Massimo Santini, Silva Severi, Luigi Oltrona Visconti, Corrado Tamburino, Roberto Zanini, Artis Kalnins, Iveta Sime, Marija Ruta Babarskiene, Dalia Jarasuniene, Birute Petrauskiene, Yolande Appelman, Ad J van Boven, Harry Suryapranata, Jurrien Ten Berg, Pim A L Tonino, Arnoud W J van 't Hof, Stanislaw Bartus, Piotr Berkowski, Boguslaw Derlaga, Jacek Dragan, Witold Dubaniewicz, Dariusz Dudek, Przemyslaw Firych, Marek Gierlotka, Jacek Gniot, Pawel Jasionowicz, Jacek Legutko, Maciej Karcz, Janusz Kochman, Jaroslaw Kosior, Hubert Krupa, Maciej Maliszewski, Jerzy Matysek, Adam Mlodziankowski, Andrzej Ochala, Jan Peruga, Krzysztof Reczuch, Radoslaw Targonski, Marek Ujda, Andrzej Wisniewski, Jaroslaw Wojcik, Maciej Zarebinski, Aleksander Zurakowski, Jorge Ferreira, Jorge Mimoso, Joao Morais, Miguel Alvares Pereira, Serban Balanescu, Dan Dobreanu, Dragos Vinereanu, Marian Hranai, Roman Margoczy, Ole Frobert, Vedat Aytekin, Mustafa Demirtas, Dogan Erdogan, Aycan Erkan, Tevfik Gurmen, Zeki Ongen, Ibrahim Ozdogru, Ertan Ural, Gilles Montalescot, Leonardo Bolognese, Dariusz Dudek, Patrick Goldstein, Christian Hamm, Jean-Francois Tanguay, Jurrien M ten Berg, Debra L Miller, Timothy M Costigan, Jochen Goedicke, Johanne Silvain, Paolo Angioli, Jacek Legutko, Margit Niethammer, Zuzana Motovska, Joseph A Jakubowski, Guillaume Cayla, Luigi Oltrona Visconti, Eric Vicaut, Petr Widimsky, ACCOAST Investigators, Gilles Montalescot, Leonardo Bolognese, Dariusz Dudek, Patrick Goldstein, Christian Hamm, Jean-Francois Tanguay, Jur ten Berg, Petr Widimsky, Marcus Flather, Alfredo Bardají, Andreas Baumbach, Miles Dalby, Akhil Kapur, François Philippe, Pierre Sabouret, Ad F van den Heuvel, Azfar Zaman, Michel Bertrand, Carlo Di Mario, Eric Vicaut, Johann Auer, Giorgio Giacomini, Kurt Huber, Franz Leisch, Thomas Neunteufl, Franz Weidinger, Christophe Beauloye, Patrick Coussement, Walter Desmet, Luc Janssens, Jacques Lalmand, Erwin Schroeder, Mathias Vrolix, Asim N Cheema, Anthony Fung, William Kostuk, Krishnan Ramanathan, Stephane Rinfret, Erick Schampaert, Jeffery Stein, Jean-Francois Tanguay, Mouhiedden Traboulsi, Ivan Hornacek, Milan Hromadka, Jozef Jakabcin, Petr Kala, Jiri Kettner, Jean-Claude Lubanda, Zuzana Motovska, Pavel Sedlon, Roman Stipal, Jan Vojacek, Juhani Airaksinen, Mika Laine, Jean Auffray, Loic Belle, Ziad Boueri, Hervé Le Breton, Pierre Carli, Guillaume Cayla, Nicolas Delarche, Axel de Labriolle, P Ecollan, Simon Elhadad, Emmanuelle Filippi, Bruno Farah, Patrick Goldstein, Pascal Goube, K Khalife, Gilles Montalescot, Jean Mouret, Laurent Payot, Carlos El Khoury, Gregoire Range, Louis Soulat, Olivier Varenne, Karl-Friedrich Appel, Martin Bergmann, Enno Boudriot, Johannes Brachmann, Gudrun Dannberg, Martin Desaga, Henning Ebelt, Evangelos Giannitsis, Rainer Gradaus, Christian Hamm, Franz Hartmann, Werner Jung, Helmut Keller, Peter Meyer, Andreas Mügge, Margit Niethammer, Christoph A Nienaber, Gert Richardt, Andreas Schäfer, Hae-Young Sohn, Nikos Werner, Andreas Zeiher, Uwe Zeymer, Peter Andreka, David Becker, Kalman Csapo, Gyorgy Fogarassy, Ivan G Horvath, Geza Lupkovics, Shaul Atar, Ariel Finkelstein, Yonathan Hasin, Basil S Lewis, Morris Mosseri, Arthur Pollak, Zvi Vered, Toni Badia, Sergio Berti, Leonardo Bolognese, Francesco Maria Bovenzi, Paola Camisasca, Claudio Cavallini, Raffaele De Caterina, Stefano De Servi, Giuseppe Fantini, Claudio Fresco, Antonio Manari, Sebastiano Marra, Ciro Mauro, Luca Olivotti, Anna Sonia Petronio, Francesco Prati, Bernhard Reimers, Massimo Santini, Silva Severi, Luigi Oltrona Visconti, Corrado Tamburino, Roberto Zanini, Artis Kalnins, Iveta Sime, Marija Ruta Babarskiene, Dalia Jarasuniene, Birute Petrauskiene, Yolande Appelman, Ad J van Boven, Harry Suryapranata, Jurrien Ten Berg, Pim A L Tonino, Arnoud W J van 't Hof, Stanislaw Bartus, Piotr Berkowski, Boguslaw Derlaga, Jacek Dragan, Witold Dubaniewicz, Dariusz Dudek, Przemyslaw Firych, Marek Gierlotka, Jacek Gniot, Pawel Jasionowicz, Jacek Legutko, Maciej Karcz, Janusz Kochman, Jaroslaw Kosior, Hubert Krupa, Maciej Maliszewski, Jerzy Matysek, Adam Mlodziankowski, Andrzej Ochala, Jan Peruga, Krzysztof Reczuch, Radoslaw Targonski, Marek Ujda, Andrzej Wisniewski, Jaroslaw Wojcik, Maciej Zarebinski, Aleksander Zurakowski, Jorge Ferreira, Jorge Mimoso, Joao Morais, Miguel Alvares Pereira, Serban Balanescu, Dan Dobreanu, Dragos Vinereanu, Marian Hranai, Roman Margoczy, Ole Frobert, Vedat Aytekin, Mustafa Demirtas, Dogan Erdogan, Aycan Erkan, Tevfik Gurmen, Zeki Ongen, Ibrahim Ozdogru, Ertan Ural
Abstract
Background: Although P2Y12 antagonists are effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes, the effect of the timing of administration--before or after coronary angiography--is not known. We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention (PCI) was indicated.
Methods: We enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after randomization. Patients were randomly assigned to receive prasugrel (a 30-mg loading dose) before the angiography (pretreatment group) or placebo (control group). When PCI was indicated, an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group.
Results: The rate of the primary efficacy end point, a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy (glycoprotein IIb/IIIa bailout) through day 7, did not differ significantly between the two groups (hazard ratio with pretreatment, 1.02; 95% confidence interval [CI], 0.84 to 1.25; P=0.81). The rate of the key safety end point of all Thrombolysis in Myocardial Infarction (TIMI) major bleeding episodes, whether related or not related to coronary-artery bypass grafting (CABG), through day 7 was increased with pretreatment (hazard ratio, 1.90; 95% CI, 1.19 to 3.02; P=0.006). The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6, respectively. Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI (69% of the patients) but increased the rate of TIMI major bleeding at 7 days. All the results were confirmed at 30 days and in prespecified subgroups.
Conclusions: Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).
Source: PubMed