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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Vorapaxar in the secondary prevention of atherothrombotic events
New England Journal of Medicine, Volume 366, No. 15, Year 2012
Notification
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Description
BACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS:At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P = 0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS:Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.) Copyright © 2012 Massachusetts Medical Society.
Authors & Co-Authors
Morrow, David A.
United States, Boston
Brigham and Women's Hospital
Braunwald, Eugene B.
United States, Boston
Brigham and Women's Hospital
Bonaca, Marc P.
United States, Boston
Brigham and Women's Hospital
Ameriso, Sebastián Francisco
Argentina, Buenos Aires
Fundacion Para la Lucha Contra Las Enfermedades Neurologicas de la Infancia
Dalby, Anthony John
South Africa, Johannesburg
Milpark Hospital
Fish, Mary Polly
United States, Boston
Brigham and Women's Hospital
Fox, Keith A.A.
United Kingdom, Edinburgh
The University of Edinburgh
Lipka, Leslie J.
United States, Rahway
Merck & Co., Inc.
Liu, Xuan
United States, Rahway
Merck & Co., Inc.
Nicolau, José Carlos
Brazil, Sao Paulo
Universidade de São Paulo
Ophuis, Anton J.Oude
Netherlands, Nijmegen
Canisius Wilhelmina Ziekenhuis
Paolasso, Ernesto Andrés C.
Unknown Affiliation
Scirica, Benjamin M.
United States, Boston
Brigham and Women's Hospital
Špinar, Jindřich
Czech Republic, Brno
Masaryk University
Thèroux, Pierre A.
Canada, Montreal
University of Montreal
Wiviott, Stephen D.
United States, Boston
Brigham and Women's Hospital
Strony, John T.
United States, Rahway
Merck & Co., Inc.
Murphy, Sabina A.
United States, Boston
Brigham and Women's Hospital
McCabe, Carolyn H.
Unknown Affiliation
Morin, S. E.
Unknown Affiliation
Lamp, Jessica M.
Unknown Affiliation
Gershman, E.
Unknown Affiliation
Deenadayalu, Naveen
Unknown Affiliation
Skene, Allan M.
Unknown Affiliation
Hill, Karen A.
Unknown Affiliation
Bennett, L.
Unknown Affiliation
Plat, Francis
Unknown Affiliation
Berman, Gary D.
Unknown Affiliation
Kilian, Ann M.
Unknown Affiliation
He, Weili
Unknown Affiliation
Aylward, Philip E.G.
Unknown Affiliation
Bassand, Jean Pierre L.
Unknown Affiliation
Betriú, Amadeo Gibert
Unknown Affiliation
Bounameaux, Henri Ruti
Unknown Affiliation
Corbalàn, Ramõn L.
Unknown Affiliation
Creager, Mark A.
Unknown Affiliation
De Ferrari, Gaetano Maria
Unknown Affiliation
Dellborg, Mikael
Unknown Affiliation
Diehm, Curt H.
Unknown Affiliation
Dietz, Rainer H.
Unknown Affiliation
Goto, Shinya
Unknown Affiliation
Grande, Peer I.
Unknown Affiliation
Hankey, Graeme J.
Unknown Affiliation
Isaza, Daniel Vanegas
Unknown Affiliation
Jensen, Peder Klosterskov
Unknown Affiliation
Kiss, Róbert Gábor
Unknown Affiliation
Lewis, Basil S.
Unknown Affiliation
Merlini, Piera Angelica
Unknown Affiliation
Moliterno, David J.
Unknown Affiliation
Morais, João Carlos Araujo
Unknown Affiliation
Nieminen, Markku Sakari
Unknown Affiliation
Nilsen, D. W.T.
Unknown Affiliation
Olin, Jeffrey W.
Unknown Affiliation
Ophuis, Ton Oude
Unknown Affiliation
Pichler, Martin
Unknown Affiliation
Shinohara, Y.
Unknown Affiliation
Teal, Phillip A.
Unknown Affiliation
Tendera, Michal B.
Unknown Affiliation
Thomassen, Lars
Unknown Affiliation
van de Werf, Frans J.J.
Unknown Affiliation
White, Harvey D.
Unknown Affiliation
Wilcox, Robert G.
Unknown Affiliation
Alberts, M.
Unknown Affiliation
Diener, Hans Christoph W.
Unknown Affiliation
Mohr, Jay Preston
Unknown Affiliation
Welch, Michael J.
Unknown Affiliation
Awtry, Eric H.
Unknown Affiliation
Berger, Claudie J.
Unknown Affiliation
Desai, Akshay Suvas
Unknown Affiliation
Gelfand, Eli V.
Unknown Affiliation
Ho, Chau Le Bao
Unknown Affiliation
Leeman, David E.
Unknown Affiliation
Link, Mark S.
Unknown Affiliation
Norden, Andrew D.
Unknown Affiliation
Pande, A.
Unknown Affiliation
Rost, Natalia Sana
Unknown Affiliation
Ruberg, R.
Unknown Affiliation
Silverman, Scott B.
Unknown Affiliation
Singhal, Aneesh Bhim
Unknown Affiliation
Vita, Joseph A.
Unknown Affiliation
Frye, Robert L.
Unknown Affiliation
Bailey, Kent R.
Unknown Affiliation
Easton, J. Donald
Unknown Affiliation
Hochman, Judith S.
Unknown Affiliation
Steg, Philippe Gabriel
Unknown Affiliation
Verheught, Freek W.A.
Unknown Affiliation
Lee, Kuanken
Unknown Affiliation
Mauro, Daniel O.
Unknown Affiliation
Centurion, A.
Unknown Affiliation
Carlevaro, Oscar
Unknown Affiliation
Cardozo, Eden R.
Unknown Affiliation
Cartasegna, Luis Rodolfo
Unknown Affiliation
Soccini, N.
Unknown Affiliation
Farras, Hilda A.
Unknown Affiliation
Molina Aguirre, E.
Unknown Affiliation
Duronto, Ernesto A.
Unknown Affiliation
Arrechavala, L.
Unknown Affiliation
Rey, Raúl Carlos
Unknown Affiliation
Stilman, A.
Unknown Affiliation
Fernández, Huberth
Unknown Affiliation
Reges, Paula P.S.
Unknown Affiliation
Cuneo, Carlos Alberto
Unknown Affiliation
MacKinnon, Ignacio J.
Unknown Affiliation
Fernández, Alberto Alfredo
Unknown Affiliation
Llanos, Javier R.
Unknown Affiliation
Casaccia, G.
Unknown Affiliation
Cirio, J. J.
Unknown Affiliation
Hominal, Miguel Angel
Unknown Affiliation
Samudio, Margarita A.
Unknown Affiliation
Prado, Aldo
Unknown Affiliation
Chew, Derek P.B.
Unknown Affiliation
Downey, Colin
Unknown Affiliation
Amerena, John V.
Unknown Affiliation
Thompson, Peter Lindsay
Unknown Affiliation
Donnan, Geoffrey Alan
Unknown Affiliation
Savage, Caroline O.S.
Unknown Affiliation
Podczeck-Schweighofer, Andrea
Unknown Affiliation
Drexel, Heinz
Unknown Affiliation
Brodmann, Marianne
Unknown Affiliation
Gaul, Georg Bernhard
Unknown Affiliation
Willeit, Johann
Unknown Affiliation
Zangerle, Alexandra
Unknown Affiliation
Kiechl, Stefan G.
Unknown Affiliation
Auer, Johann W.
Unknown Affiliation
Ammer, Marcus
Unknown Affiliation
Motte, Serge
Unknown Affiliation
Schroé, Herman H.
Unknown Affiliation
Vermassen, Frank E.G.
Unknown Affiliation
de Deyn, Peter Paul
Unknown Affiliation
Vandermeeren, Yves
Unknown Affiliation
Pandolfo, Massimo
Unknown Affiliation
Peeters, André Philippe
Unknown Affiliation
Thijs, Vincent N.S.
Unknown Affiliation
Verhamme, Peter B.
Unknown Affiliation
Sinnaeve, Peter R.
Unknown Affiliation
Maia, Lília Nigro
Unknown Affiliation
Dutra, Óscar Pereira
Unknown Affiliation
Marin-Neto, José Antonio
Unknown Affiliation
Piegas, Leopoldo Soares
Unknown Affiliation
Gagliardi, Rubens José
Unknown Affiliation
Saraiva, José Francisco Kerr
Unknown Affiliation
Speciali, José Geraldo
Unknown Affiliation
Abrantes, José Antonio M.
Unknown Affiliation
Teixeira, Marcelo Silveira
Unknown Affiliation
Resende, Ederlon S.
Unknown Affiliation
Barbosa, Eduardo Costa Duarte
Unknown Affiliation
Faria-Neto, José Rocha
Unknown Affiliation
Hernandes, Mauro Esteves
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Kouz, Simon M.
Unknown Affiliation
Gosselin, Gilbert
Unknown Affiliation
Chan, Yih Kai
Unknown Affiliation
Bélisle, Patrick
Unknown Affiliation
Muñoz, Alberto
Unknown Affiliation
Madan, Mina
Unknown Affiliation
Bata, Iqbal R.
Unknown Affiliation
Ma, Patrick T.S.
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Lamy, Andre L.
Unknown Affiliation
Welsh, Robert C.
Unknown Affiliation
Lindholm, Lars Hjalmar J.
Unknown Affiliation
Gupta, Milan K.
Unknown Affiliation
Nguyen, Michel
Unknown Affiliation
Cantor, Warren J.
Unknown Affiliation
McPherson, Charles E.
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Prieto, Juan Carlos D.
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Mendoza, Floreliz H.
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Martinez, Solange
Unknown Affiliation
Martínez, Julio Acosta
Unknown Affiliation
Jaramillo, Mónica Lopez
Unknown Affiliation
Urina-Triana, Miguel
Unknown Affiliation
Castaño, Luís Antonio
Unknown Affiliation
Accini, José Luis
Unknown Affiliation
Reynales, Humberto
Unknown Affiliation
Filipovsky, Jan
Unknown Affiliation
Hirmerová, Jana
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Kañovský, Peter
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Herzig, Roman
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Janský, Petr
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Monhart, Zdeněk
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Linhart, Aleš
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Hlinomaz, Ota
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Pařenica, Jiří
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Souĉek, Miroslav
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Branný, Marián
Unknown Affiliation
Klimsa, Zdeněk
Unknown Affiliation
Mikulík, Robert
Unknown Affiliation
Mayer, Otto
Unknown Affiliation
Polášek, Rostislav
Unknown Affiliation
Iversen, Helle Klingenberg
Unknown Affiliation
Christensen, Hanne Krarup
Unknown Affiliation
Husted, Steen Elkjær
Unknown Affiliation
Mickley, Hans F.
Unknown Affiliation
Andersen, Grethe K.
Unknown Affiliation
Jeppesen, Jørgen Lykke
Unknown Affiliation
Airaksinen, Juhani K.E.
Unknown Affiliation
Vasankari, Tommi Juhani
Unknown Affiliation
Tatlisumak, Turgut
Unknown Affiliation
Galinier, Michel C.
Unknown Affiliation
Elbaz, Meyer
Unknown Affiliation
Montalescot, Gilles
Unknown Affiliation
Hamon, Martial
Unknown Affiliation
Amarenco, Pierre
Unknown Affiliation
Timsit, S. G.
Unknown Affiliation
Queŕé, Isabelle
Unknown Affiliation
Emmerich, Joseph D.
Unknown Affiliation
Moulin, T.
Unknown Affiliation
Hosseini, Hassan H.
Unknown Affiliation
Cöttin, Yves
Unknown Affiliation
Bichat, Florence
Unknown Affiliation
Samson, Yves
Unknown Affiliation
Bura-Rivière, Alessandra
Unknown Affiliation
Giroud, Maurice E.
Unknown Affiliation
Ohlmann, Patrick
Unknown Affiliation
Darius, Harald
Unknown Affiliation
Felix, Stephan Burkhard
Unknown Affiliation
Nienaber, Christoph Anton
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Konstantinides, Stavros V.
Unknown Affiliation
Kreuzer, Jörg G.
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Zeiher, Andreas Michael
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Ringleb, Peter Arthur
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Rosenkranz, Michael
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Maschke, Matthias
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Hoffmann, Udo
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Grond, Martin
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Schellong, Sebastian M.
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Dichgans, Martin
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Blank, Evan
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Diószeghy, Péter
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Bornstein, Natan M.
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Chajek-Shaul, Tova
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Bursztyn, Michael
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Gavish, Dov
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Wexler, Deborah J.
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Tanne, David
Unknown Affiliation
Eldar, Michael
Unknown Affiliation
Zimlíchman, Reuven R.
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Gottlieb, Shmuel L.
Unknown Affiliation
Elis, Avishay
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Hussein, Osamah A.
Unknown Affiliation
Brenner, Hermann
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Gavazzi, Antonello
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Marenzi, Giancarlo
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Specchia, Giuśeppe
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Golino, Paolo
Unknown Affiliation
Cianflone, Domenico
Unknown Affiliation
Tamburino, Corrado
Unknown Affiliation
Rubartelli, Paolo
Unknown Affiliation
Ardissino, Diego
Unknown Affiliation
Stramba-Badiale, Marco
Unknown Affiliation
Azzarelli, Salvatore Adriano
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Esposito, Giovanni
Unknown Affiliation
Cassese, Salvatore
Unknown Affiliation
Fattore, Luciano
Unknown Affiliation
De Caterina, Raffaele
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Odero, Attilio
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Marcheselli, Simona
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Geraci, Giovanna
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Pitì, Antonino
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Terrosu, Pierfranco
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Marconi, Roberto
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Agnelli, Giancarlo
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Novo, Salvatore
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Uchiyama, Shinichiro
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Ong, Tiongkiam
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Dunselman, Peter H.J.M.
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Westendorp, P.
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van Hessen, Maarten W.J.
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Schut, Astrid
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Swart, Hendrik P.
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Ronner, Eelko F.
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Basart, Dick C.G.
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Ten Berg, Jurriën Maria
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Groenemeijer, Björn E.
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Heymeriks, J.
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Jukema, Johan Wouter
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Singh, Gurminder P.
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Larsen, Torben B.
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Statistics
Citations: 850
Authors: 301
Affiliations: 9
Identifiers
Doi:
10.1056/NEJMoa1200933
ISSN:
00284793
Research Areas
Environmental
Noncommunicable Diseases
Study Design
Case-Control Study