Published Online: March 11, 2013. doi:10.1001 /jama.2013.1954
AuthorContributions: Dr Gheorghiade had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Gheorghiade, Böhm, Fonarow, Lewis, Zannad, Solomon, Hua, Gimpelewicz, Maggioni.
Acquisition of data: Gheorghiade, Böhm, Fonarow, Lewis, Baschiera, Hua, Gimpelewicz, Jaumont, Lesogor.
Analysis and interpretation of data: Gheorghiade, Böhm, Greene, Fonarow, Zannad, Solomon, Baschiera, Botha, Hua, Gimpelewicz, Jaumont, Lesogor, Maggioni.
Drafting of the manuscript: Gheorghiade, Greene, Baschiera, Hua, Gimpelewicz, Jaumont, Lesogor.
Critical revision of the manuscript for important intellectual content: Gheorghiade, Böhm, Greene, Fonarow, Lewis, Zannad, Solomon, Baschiera, Botha, Hua, Gimpelewicz, Lesogor, Maggioni.
Statistical analysis: Botha, Hua.
Administrative, technical, or material support: Gheorghiade, Baschiera, Jaumont, Lesogor.
Study supervision: Gheorghiade, Fonarow, Lewis, Baschiera, Lesogor, Maggioni.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Gheorghiade reported serving as a consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer Schering Pharma, Bayer HealthCare, Cardiorentis, CorThera, Cytokinetics, CytoPherx, DebioPharm, Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Intersection Medical, INC, Johnson and Johnson, Medtronic, Merck, Novartis Pharma, Ono Pharma USA, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, sanofi-aventis, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT, Takeda Pharmaceuticals, and Trevena Therapeutics. Dr Böhm reported serving as a consultant for AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, sanofi-aventis, Servier, and Medtronic and on speakers' bureaus for AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, AWD Dresden, Berlin-Chemie, MSD, Novartis, Pfizer, sanofi-aventis, and Servier. Dr Fonarow reported receiving grant funding from GlaxoSmithKline, the National Institutes of Health, and the Agency for Healthcare Research and Quality; serving on speakers' bureaus for Boston Scientific/Guidant, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, and St Jude Medical; and serving as a consultant for Amgen, Gambro, GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, Relypsa, Scios, St Jude Medical, Medicines Company, Johnson and Johnson, and Takeda. Dr Fonarow holds the Eliot Corday Chair of Cardiovascular Medicine at UCLA and is also supported by the Ahmanson Foundation. Dr Lewis reported receiving grant funding and other support from Novartis. Dr Zannad reported receiving grant funding from Novartis, BG Medicine, and Roche Diagnostics; serving on speakers' bureaus for Pfizer and AstraZeneca; serving on a board for Boston Scientific; and serving as a consultant for Novartis, Takeda, AstraZeneca, Boehringer-Ingelheim, GE Healthcare, Relypsa, Servier, Boston Scientific, Bayer, Johnson and Johnson, and ResMed. Dr Solomon reported receiving grant funding, consulting fees, and travel support from Novartis. Dr Baschiera reported receiving consulting fees, travel support, stock options, and other funding from Novartis Pharma, where he is an employee. Mr Botha reported receiving consulting fees, travel support, and other funding from Novartis Pharma, where he is an employee. Dr Hua reported receiving travel support and stock options from Novartis Pharma, where he is an employee. Dr Gimpelewicz reported being an employee of Novartis and receiving stock and stock options from Novartis. Dr Jaumont reported receiving consulting fees, travel support, stock options, and other funding from Novartis Pharma, where he is an employee. Dr Lesogor reported receiving consulting fees, travel support, stock options, and other funding from Novartis Pharma, where she is an employee. Dr Maggioni reported serving as a consultant for Bayer, Amgen, Cardiorentis, and Johnson and Johnson; receiving grants from Novartis, Medtronic, and Abbott; and receiving consulting fees and travel support from Novartis Pharma. No other disclosures were reported.
Funding/Support: The ASTRONAUT study is funded by Novartis Pharma AG, Basel, Switzerland, under the guidance of the ASTRONAUT Executive Committee.
Role of the Sponsor: Novartis participated in the design, conduct, and management of the study; the collection of the data; and the preparation, review, and approval of the manuscript. Novartis had no role in the analysis and interpretation of the data.
Independent Statistical Analysis: The data were analyzed independently and validated by Timothy Collier, BSc, MSc, who holds an appointment in the Department of Medical Statistics, London School of Hygiene and Tropical Medicine. Mr Collier was given full access to all the raw data, derived data, programs, and output for all the results that would be included in the manuscript. The independent statistical analysis consisted of confirming that the statistical methods used were as prespecified in the protocol and statistical analysis plans; checking the validity of the various analysis patients sets, eg, randomized set, full analysis set, safety set, and derived data; writing and executing programs to carry out the specified statistical analysis; and comparing the results from these analyses with those obtained by Novartis. Mr Collier confirmed that the statistical methods used were as specified in the statistical analysis plan, that the full analysis and safety sets used in the analyses were appropriate, and that the results he obtained were in full agreement with those presented in the manuscript. The independent, validated analysis was fully consistent with that of the sponsor and constitutes the results reported in this article. Mr Collier was remunerated for his work by the sponsor.
ASTRONAUT Trial Investigators: Silvina Ramos, Alejandra Luna, Santiago Miriuka, Mirta Diez, Eduardo Perna, Hugo Luquez, Jorge Garcia Pinna, Jorge Castagnino, Pablo Alvarenga, Julio Ibañez, Eduardo Salmon Blumberg, Claudio Dizeo, Rodolfo Ahuad Guerrero, Pablo Schygiel, Rodolfo Milesi, Carlos Sosa, Miguel Hominal, Lilia Lobo Marquez, Carlos Poy, Eduardo Hasbani, Marisa Vico, Alberto Fernandez, Nestor Vita (Argentina); Johan Vanhaecke, Gilles De Keulenaer, Harry Striekwold, Geert Vervoort, Mathias Vrolix, Philippe Henry, Paul Dendale, Walter Smolders, Patrick Marechal, Hans Vandekerckhove (Belgium); Mucio Oliveira Jr, Fernando Neuenschwande, Gilmar Reis, Jose Saraiva, Luiz Bodanese, Manoel Canesin, Oswaldo Greco, Roberto Bassan, Roberto Luis Marino (Brazil); Nadia Giannetti, Gordon Moe, Bruce Sussex, Richard Sheppard, Thao Huynh, Robert Stewart, Haissam Haddad (Canada); Luis Echeverria, Adalberto Quintero, Adriana Torres, Mónica Jaramillo, Mónica Lopez, Fernan Mendoza, Noel Florez, Carlos Cotes, Magali Garcia (Colombia); Jan Belohlavek, Jaromir Hradec, Martin Peterka, Pavel Gregor, Zdenek Monhart, Petr Jansky, Jiri Kettner, Petr Reichert, Jindrich Spinar, Tomas Brabec, Martin Hutyra, Miroslav Solar (Czech Republic); Mikko Pietilä, Kai Nyman, Risto Pajari (Finland); Ariel Cohen, Michel Galinier, Philippe Gosse, Bernard Livarek, Yannick Neuder, Patrick Jourdain, François Picard, Richard Isnard (France); Uta Hoppe, Stefan Kaeaeb, Stefan Rosocha, Roland Prondzinsky, Stephan Felix, Hans-Dirk Duengen, Hans-Reiner Figulla, Sven Fischer, Steffen Behrens, Philipp Stawowy, Juergen Kruells-Muench, Fabian Knebel, Christoph Nienaber, Dierk Werner, Wilma Aron, Bjoern Remppis, Rainer Hambrecht, Klaus Kisters, Nikos Werner, Stefan Hoffmann, Siegbert Rossol, Ernst Geiss, Kristof Graf, Frank Hamann, Wolfgang von Scheidt, Robert Schwinger, Ulrich Tebbe, Angelika Costard-Jaeckle, Stephan Lueders, Thomas Heitzer, Marie-Louise Leutermann-Oei, Ruediger Braun-Dullaeus, Jens-Uwe Roehnisch, Gerhard Muth, Andreas Goette, Achim Rotter, Henning Ebelt, Hans-Georg Olbrich, Veselin Mitrovic, Christian Hengstenberg, Sebastian Schellong (Germany); Karoly Zamolyi, Andras Vertes, Andras Matoltsy, Attila Palinkas, Bela Herczeg, Dezso Apro, Geza Lupkovics, Janos Tomcsanyi, Kalman Toth (Hungary); Atul Mathur, Darshan Banker, Anil Bharani, Jaspal Arneja, Aziz Khan, Milind Gadkari, Jagdish Hiremath, Nitin Patki, Makund Kumbla, M.J. Santosh, A.G. Ravikishore, Rajpal Abhaichand, Vijayakukmar Maniyal, Manjunath Nanjappa, P. Naveen Reddy, Kulasekaran Chockalingam, Rajendra Premchand, Vijay Mahajan (India); Basil Lewis, Dov Wexler, Michael Shochat, Andre Keren, Muhamad Omary, Amos Katz, Alon Marmor (Israel); Giuseppe Lembo, Salvatore Di Somma, Alessandro Boccanelli, Mario Barbiero, Giuseppe Pajes, Stefano De Servi, Dott Cosimo Greco, Fernando De Santis, Agata Floresta, Luigi Oltrona Visconti, Giancarlo Piovaccari, Claudio Cavallini, Matteo Di Biase, Dott Franco Masini, Corrado Vassanelli, Maurizio Viecca, Dott Francesco Cangemi, Salvatore Pirelli, Claudio Borghi, Massimo Volpe, Angelo Branzi, Dott Giovanni Percoco, Silvia Severi, Alberto Santini, Ettore De Lorenzi, Marco Metra, Valerio Zacà, Andrea Mortara (Italy); Francisco P. Tranquilino, Noe A. Babilonia, Arthur M. Ferrolino, Benjamin Manlutac Jr (Philippines); Miroslaw Dluzniewski, Zofia Dzielinska, Ewa Nowalany-Kozie, Walentyna Mazurek, Jerzy Wierzchowiecki, Andrzej Wysokinski, Joanna Szachniewicz, Witold Romanowski, Magdalena Krauze-Wielicka, Piotr Jankowski, Piotr Berkowski, Jaroslaw Kasprzak, Roman Szelemej, Andrzej Kleinrok, Zdzislawa Kornacewicz-Jac (Poland); Marius Vintila, Mircea Vladoianu, Constantin Militaru, Gheorghe Dan, Maria Dorobantu, Stefan Dragulescu (Romania); Victor Kostenko, Alexandr Vishnevsky, Boris Goloschekin, Vadim Tyrenko, Alexander Gordienko, Oxana Kislyak, Sergey Martsevich, Alexey Kuchmin, Yurii Karpov, Igor Fomin, Yury Shvarts, Olga Orlikova, Olga Ershova, Olga Berkovich, Maria Sitnikova, Inna Pakhomova, Svetlana Boldueva, Tatiana Tyurina, Vladimir Simanenkov, Mikhail Boyarkin, Nina Novikova, Sergey Tereschenko, Vladimir Zadionchenko, Zaur Shogenov, Ivan Gordeev, Valentin Moiseev (Russia); Raymond Wong, Hean Yee Ong, Ju Le Tan (Singapore); Eva Goncalvesova, Frantisek Kovar, Ivan Skalina, Viera Kasperova, Silvia Hojerova, Miroslav Szentivanyi, Branislav Stancak, Marian Babcak, Peter Kycina, Pavol Poliacik, Peter Toth, Jana Sirotiakova (Slovakia [Slovak Republic]); Esteban Lopez de Sa, Manuel Gomez Bueno, Manuel Martinez Selles, Jose Angel Cabrera, Ramon Bover Freire, Jose Ramon Gonzalez Juanatey, Josep Comin, Francisco Ridocci Soriano, Alejandro Lopez, Raul Vicho, Manuel Geraldia Lama (Spain); Maria Schaufelberger, Richard Brunotte, Bengt Ullman, Inger Hagerman, Stella Cizinsky (Sweden); Wen-Jin Cherng, Wen-Chung Yu, Chi-Tai Kuo, Kuan-Cheng Chang, Wen-Ter Lai, Jen-Yuan Kuo (Taiwan); Dilek Ural, Ozer Badak, Mustafa Akin, Zerrin Yigit, Mehmet Yokusoglu, Mehmet Yilmaz, Adnan Abaci, Haksun Ebinc (Turkey); Richard Perlman, David Parish, James Bergin, Kenneth Burnham, Christopher Brown, Justin Lundbye, Celeste Williams, Howard Eisen, Elizabeth Juneman, Susan Joseph, Mary Ann Peberdy, Jennifer Peura, Vishal Gupta, Kalim Habet, William French, Freny Mody, Susan Graham, Monica Hazelrigg, Eugene Chung, Stephanie Dunlap, Lazaros Nikolaidis, Samer Najjar, Richard Katz, Srinivas Murali, Joseph L. Izzo, Tracy Callister, Roland Phillips, Nicholas Lippolis, John Winterton, Sheba Meymandi, Karl Heilman III, Ron Oren, Ronald Zolty, Michael Brottman, D.R. Gunawardena, Kirkwood Adams, Denise Barnard, Marc Klapholz, James Fulmer (United States). Study Executive Committee: Mihai Gheorghiade (Chair), Aldo P. Maggioni (Co-Chair), Michael Böhm, Gregg C. Fonarow, Faiez Zannad. Study Data Monitoring Committee: Karl Swedberg (Chair), Jeffrey S. Borer, Bertram Pitt, Stuart Pocock, Jean Rouleau. Central End Point Committee: Scott D. Solomon (Chair), Eldrin F. Lewis, Peter Finn, Howard Hartley, Larry Weinrauch, Ebrahim Barkoudah, Kayode Odutayo.
Additional Contributions: We thank Pravin Bolshete, BAMS, MSc (Novartis Healthcare, Hyderabad, India), for his help in formatting the manuscript, tables, and figures. He is a Novartis employee but was not compensated additionally for his contribution.
This article was corrected for errors on March 19, 2013