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198 results on '"Hendrix E."'

2. On conceptualisation and an overview of learning path recommender systems in e-learning

Author

Fuster-López, A., Cruz, J. M., Guerrero-García, P., Hendrix, E. M. T., Košir, A., Nowak, I., Oneto, L., Sirmakessis, S., Pacheco, M. F., Fernandes, F. P., and Pereira, A. I.

Subjects
Computer Science - Information Retrieval, Computer Science - Artificial Intelligence, Computer Science - Machine Learning
Abstract

The use of e-learning systems has a long tradition, where students can study online helped by a system. In this context, the use of recommender systems is relatively new. In our research project, we investigated various ways to create a recommender system. They all aim at facilitating the learning and understanding of a student. We present a common concept of the learning path and its learning indicators and embed 5 different recommenders in this context.

Published
2024

3. On Polytopal Branch and Bound with Monotonicity

Author

Hendrix, E. M. T., Casado, L. G., G.-Tóth, B., Messine, F., Goos, Gerhard, Series Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Gervasi, Osvaldo, editor, Murgante, Beniamino, editor, Garau, Chiara, editor, Taniar, David, editor, C. Rocha, Ana Maria A., editor, and Faginas Lago, Maria Noelia, editor

Published
2024
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4. On Monotonicity Detection in Simplicial Branch and Bound over a Simplex

Author

Casado, L. G., G.-Tóth, B., Hendrix, E. M. T., Messine, F., Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Gervasi, Osvaldo, editor, Murgante, Beniamino, editor, Misra, Sanjay, editor, Rocha, Ana Maria A. C., editor, and Garau, Chiara, editor

Published
2022
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8. P189 Lifestyle and psychosocial factors in IBD; prevalence and patients’ perspective

Author

Demers, K, primary, Hendrix, E M B, additional, Rezazadeh Ardabili, A, additional, Bredero, Q M, additional, van Bodegraven, A A, additional, van der Horst, D, additional, Jonkers, D M A E, additional, Kimman, M L, additional, Mujagic, Z, additional, Romberg-Camps, M J, additional, Römkens, T E H, additional, Scherpenzeel, M P, additional, Schroevers, M J, additional, Stassen, L P S, additional, West, R L, additional, Dijkstra, G, additional, and Pierik, M J, additional

Published
2024
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10. Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial

Author

Sabatine, Marc S, Wiviott, Stephen D, Scirica, Benjamin M, Inzucchi, Silvio, Keech, Anthony, McGuire, Darren K, Smith, Steven R, Satlin, Andrew, Brown, Conville, Budaj, Andrzej, Corbalan, Ramon, Dwyer, Jamie, Garcia-Castillo, Armando, Gupta, Milan, Hamm, Christian, Kaplan, Lee, Leiter, Lawrence A, Nicolau, Jose Carlos, Oude Ophuis, Ton, Ray, Kauski, Ruda, Mikhail, Spinar, Jindrich, Weissman, Neil, White, Harvey D, Amerena, J, Arstall, M, Colquhoun, D, Jayasinghe, R, Lee, A, Lehman, R, Moses, R, Proietto, J, Purnell, P, Waites, J, Blombery, P, Cross, D, Worthley, M, d'Emden, M, Selvanayagam, J, Oqueli, RE, Whelan, A, Garrahy, P, de Looze, F, Ninio, D, Horowitz, J, William, M, Suranyi, M, Wittert, G, Le May, M, Pandey, AS, Vizel, S, Labonte, R, Beaudry, Y, Fortin, C, Bell, A, Kouz, S, St-Amour, É, Bata, I, St Maurice, F, Chehayeb, R, Constance, C, Wong, G, Hess, A, Liutkus, J, Poirier, P, Teitelbaum, I, Berlingieri, J, Cha, J, Hartleib, M, Heffernan, M, Twum-Barima, D, Pandith, V, Aronson, R, Goldenberg, R, Ajala, B, Jain, A, Ross, S, Bajaj, H, Khandwala, H, Yared, Z, Gupta, N, Bédard, J, Wharton, S, Blouin, F, Savard, D, Shukla, D, Cobos, J, Godoy, G, Perez, L, Pincetti, C, Saavedra Guajardo, V, Varleta, P, Conejeros, C, Lanas, F, Bayram Llamas, E, Cardona Muñoz, E, Garcia, R, Garza Ruiz, J, Llamas Esperon, G, Lopez Rosas, E, Melendez Mier, G, Ramos, G, Hart, H, Scott, D, Ternouth, I, Benatar, J, Elliott, J, Cutfield, R, Manning, P, Williams, M, Ferrier, K, Scott, R, Wilson, S, Leikis, R, Nirmalaraj, BK, Krzyżagórska, E, Miękus, P, Bronisz, M, Mirek-Bryniarska, E, Łanda, K, Stasiewski, A, Żechowicz, T, Zytkiewicz-Jaruga, D, Korecki, J, Ogórek, M, Pawłowicz, L, Piepiorka, M, Skierkowska, J, Stankiewicz, A, Szyprowska, E, Witek, R, Bochenek, A, Kończakowski, P, Wojnowski, Ł, Wujkowski, M, Cymerman, K, Korzeniak, R, Mąder, P, Mikłaszewicz, B, Stachlewski, P, Goch, A, Pomiećko, W, Skórski, M, Romanowski, L, Jusiak, K, Laskowska-Derlaga, E, Bijata-Bronisz, R, Kaźmierczak, J, Goldberg, R, Henderson, D, Korban, E, Rohr, K, Claxton, E, Weiss, R, Angiolillo, D, Boccalandro, F, Chu, K, Thorn, E, Randhawa, P, Singh, N, Bittar, G, Guarnieri, T, Saeed, S, Sharma, S, Shepard, M, French, W, Desai, P, Bernstein, R, Rogers, W, Singal, R, Schneider, R, Shanes, J, Ong, S, Condit, J, Donahoe, S, Brill, D, Einhorn, D, Ebrahimi, R, Labroo, A, Graf, R, Scott, J, Hoekstra, J, Jetty, P, Luckasen, G, O'Donnell, P, Gonte, W, Pomposini, D, Quadrel, M, Koren, M, Schlager, D, Schramm, E, Singal, D, Lupovitch, S, Soni, A, Seigel, P, Roberts, J, Soufer, J, Reza, S, Quinlan, E, Moretto, T, First, B, Khan, M, Chilka, S, Colfer, H, Teklinski, A, Wallace-Wilding, K, Ellison, H, Muse, D, Aronoff, S, Higgins, A, Patel, S, Elinoff, V, Karim, A, Awasty, V, Chuang, R, Roseman, H, Dugano-Daphnis, P, Albert, M, Sheikh, K, Bays, H, Kaster, S, Goldstein, M, Rubino, D, Calatayud, G, Snyder, H, Williams, T, Hershon, K, Hagan, M, Isserman, S, Kahn, B, Anderson, J, Gimness, MP, Raisinghani, A, Christina, M, Raikhel, M, Gillespie, E, Portnay, E, Heiman, M, Qureshi, M, Lee, J, Blonder, R, Cucher, F, Miller, G, Kotlaba, D, Cornett, G, Beavins, J, Augenbraun, C, Reinhardt, S, Bartkowiak, A, Jr, Salacata, A, Blevins, T, Benjamin, S, Diener, J, George, W, Barker, B, Richwine, R, Baldari, D, Alfieri, A, Barreto, A, Zhang, L, Shah, R, Hendrix, E, Subramaniyam, V, Hurley, S, Lillestol, M, O'Donoghue, M, Shayani, S, Ryan, E, Call, R, Zemel, L, Chang, A, Kivitz, A, Freyne, B, Bland, V, Shore, K, Mostel, E, Uzoaga, E, Andrawis, N, Gabra, N, Ghitis, A, Sabatino, K, Browder, D, Varma, S, Smith, S, Fink, R, Aycock, GR, Jr, Doty, WD, Alfonso, T, Eshaghian, S, Karlsberg, R, Zarich, S, Landau, C, McKenzie, M, Krause, R, Davis, W, Haddad, T, Voyce, S, Alford, C, LeDoux, J, O'Dea, D, Park, J, Aroda, V, Getaneh, A, Graham, B, Bhagwat, R, Korn, D, Ruoff, G, Wiseman, A, Lieber, I, Fialkow, J, Gonzalez-Campoy, JM, Bayron, C, Bertolet, B, Lash, J, Gerrish, C, Robertson, D, Rosenfeld, J, Seidner, M, Agaiby, J, Silverfield, J, Sugimoto, D, Lubin, B, Alhaddad, M, Lui, H, Lakin, G, Chokshi, S, Donovan, D, Felten, W, Minton, S, Kimmelstiel, C, Kuvin, J, Still, C, Byars, W, Talano, J, Desai, V, Bradley, AJ, III, Baker, S, Chane, M, Mercado, A, Baron, S, Harris, B, Mayer, N, Concha, M, Carr, K, Chaykin, L, Willis, J, Clay, A, Fenstad, E, Furda, J, Peterson, P, Chang, M, Aronne, L, Jones, D, Prashad, R, Benson, M, Stegemoller, R, Longshaw, K, Saleh, J, Jennings, W, Detweiler, R, Viswanath, D, Patel, R, Lederman, S, Weinstein, D, Korabathina, R, Singh, V, Rosen, J, Estevez, R, Levin, P, McNeill, R, Kalen, V, Reed, J, Ashley, R, Herman, L, Tsai, Y, Kayne, D, White, A, Hussain, I, Tami, L, Cohen, K, Robinson, J, Fuchs-Ertman, D, Platt, G, Belardo, L, Reddy, R, Rosendorff, C, Saba, F, Powell, S, Anderson, K, Abidi, M, Rezkalla, S, Paraschos, A, Wilson, J, Moursi, M, Shah, A, Nadar, V, Stonesifer, L, Bialow, M, Cannon, K, Ellison, W, Stedman, M, Brown, J, Harper, W, Lucas, KJ, DiGiovanna, M, Rodbard, H, Biscoveanu, M, Davis, C, Hall, J, Littlefield, R, Gorman, T, Kereiakes, D, Chang, FM, Tatu, H, Cheung, D, Kaine, J, Knutson, T, Logemann, T, Pueblitz, G, Bianco, J, Henson, B, Neustel, M, Gelernt, M, Nelson, W, Moriarty, K, Lefebvre, G, Maw, K, Rink, L, Behn, P, Studdard, H, Argoud, G, O'Connor, T, Krichmar, P, Raad, G, Pereles-Ortiz, J, Sorli, C, Cohen, A, Pettis, K, Cavanaugh, B, Phillips, C, Wahlen, J, Radin, D, Rider, J, Kosinski, E, Leimbach, W, Odhav, A, Hakas, J, Tan, A, Howell, M, Wombolt, D, Fishman, N, Shah, P, Wylie, P, Arauz-Pacheco, C, Cavale, A, George, A, Kroll, R, Krantzler, J, Tahirkheli, N, Jabro, M, Newell, M, Mullen, P, Gencheff, N, Meli, J, Vora, K, Kotek, L, Pyzdrowski, K, Paez, H, Moran, J, Tannenbaum, A, Deck, K, Busch, R, Levinson, L, Azizad, M, Whitaker, J, Fox, B, Huffman, C, Ashraf, M, Diogo, J, Kushner, R, Tallet, J, Channamsetty, V, Suh, D, Atieh, M, Navas, J, Young, V, Shaw, S, Dor, I, Duffy, B, Rubin, P, Lewis, D, Kaye, W, Benton, R, Burbano, J, Hotchkiss, D, Magno, A, Alberton, A, Collins, J, Alvarado, O, Stich, M, Mahal, S, Liu, J, Hong, M, Dy, J, Block, B, Lamantia, J, Pritchard, J, Davis, M, Srivastava, S, Bilazarian, S, Rosario, R, McCartney, M, Blumberg, V, Rajan, R, Martin, E, Wright, S, Brinson, C, Johnston, J, Graves, M, Dominguez, M, McKenzie, W, Abadier, R, Tran, C, Castello, R, Morawski, E, White, J, Morris, F, Perez, A, Trueba, P, Sanchez, M, Andersen, J, Kastelic, R, Khan, J, Rodriguez, H, Izquierdo, W, Matias, A, Essandoh, L, Ince, C, Bohula, Erin A, Inzucchi, Silvio E, Keech, Anthony C, Kanevsky, Estella, Murphy, Sabina A, Dwyer, Jamie P, Ophuis, Ton Oude, Ray, Kausik K, Patel, Tushar, Miao, Wenfeng, Perdomo, Carlos, Francis, Bruce, Dhadda, Shobha, Bonaca, Marc P, and Ruff, Christian T

Published
2018
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11. On Grid Aware Refinement of the Unit Hypercube and Simplex: Focus on the Complete Tree Size

Author

Casado, L. G., Hendrix, E. M. T., Salmerón, J. M. G., G.-Tóth, B., García, I., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Gervasi, Osvaldo, editor, Murgante, Beniamino, editor, Misra, Sanjay, editor, Borruso, Giuseppe, editor, Torre, Carmelo M., editor, Rocha, Ana Maria A.C., editor, Taniar, David, editor, Apduhan, Bernady O., editor, Stankova, Elena, editor, and Cuzzocrea, Alfredo, editor

Published
2017
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23. Insight into the Initial Stages of the Folding Process in Onconase Revealed by UNRES

Author

Hendrix, E, Motta, S, Gahl, R, He, Y, Hendrix, Emily, Motta, Stefano, Gahl, Robert F, He, Yi, Hendrix, E, Motta, S, Gahl, R, He, Y, Hendrix, Emily, Motta, Stefano, Gahl, Robert F, and He, Yi

Abstract

The unfolded state of proteins presents many challenges to elucidate the structural basis for biological function. This state is characterized by a large degree of structural heterogeneity which makes it difficult to generate structural models. However, recent experiments into the initial folding events of the 104-residue ribonuclease homologue onconase (ONC) were able to identify the regions in the protein that participate in the initial folding of this protein. Therefore, to gain additional structural insight into the unfolded state of proteins, this study utilized molecular dynamics simulations using the UNited-RESidue (UNRES) force field to evaluate whether there is a good agreement between the experimentally determined initial structures and the structures identified by computer simulations along a folding pathway. Indeed, these UNRES simulations accurately identified the two regions experimentally observed to form the initial native structure along the folding pathway of ONC. In addition, these regions are determined to be chain folding initiation sites (CFIS) according to methods developed previously. Subsequent self-organization maps (SOM) analysis has revealed key structural states involved in these early folding events.

Published
2022

24. Recognizing the Binding Pattern and Dissociation Pathways of the p300 Taz2-p53 TAD2 Complex

Author

Li, T, Motta, S, Stevens, A, Song, S, Hendrix, E, Pandini, A, He, Y, Li, Tongtong, Motta, Stefano, Stevens, Amy O, Song, Shenghan, Hendrix, Emily, Pandini, Alessandro, He, Yi, Li, T, Motta, S, Stevens, A, Song, S, Hendrix, E, Pandini, A, He, Y, Li, Tongtong, Motta, Stefano, Stevens, Amy O, Song, Shenghan, Hendrix, Emily, Pandini, Alessandro, and He, Yi

Abstract

The dynamic association and dissociation between proteins are the basis of cellular signal transduction. This process becomes much more complicated if one or both interaction partners are intrinsically disordered because intrinsically disordered proteins can undergo disorder-to-order transitions upon binding to their partners. p53, a transcription factor with disordered regions, plays significant roles in many cellular signaling pathways. It is critical to understand the binding/unbinding mechanism involving these disordered regions of p53 at the residue level to reveal how p53 performs its biological functions. Here, we studied the dissociation process of the intrinsically disordered N-terminal transactivation domain 2 (TAD2) of p53 and the transcriptional adaptor zinc-binding 2 (Taz2) domain of transcrip-tional coactivator p300 using a combination of classical molecular dynamics, steered molecular dynamics, self-organizing maps, and time-resolved force distribution analysis (TRFDA). We observed two different dissociation pathways with different probabilities. One dissociation pathway starts from the TAD2 N-terminus and propagates to the alpha-helix and finally the C-terminus. The other dissociation pathway is in the opposite order. Subsequent TRFDA results reveal that key residues in TAD2 play critical roles. Besides the residues in agreement with previous experimental results, we also highlighted some other residues that play important roles in the disassociation process. In the dissociation process, non-native interactions were formed to partially compensate for the energy loss due to the breaking of surrounding native interactions. Moreover, our statistical analysis results of other experimentally determined complex structures involving either Taz2 or TAD2 suggest that the binding of the Taz2-TAD2 complex is mainly governed by the binding site of Taz2, which includes three main binding regions. Therefore, the complexes involving Taz2 may follow similar binding

Published
2022

33. Dapagliflozin and cardiovascular outcomes in type 2 diabetes

Author

Wiviott, S, Raz, I, Bonaca, M, Mosenzon, O, Kato, E, Cahn, A, Silverman, M, Zelniker, T, Kuder, J, Murphy, S, Bhatt, D, Leiter, L, Mcguire, D, Wilding, J, Ruff, C, Nilsson, G, Fredriksson, M, Johansson, P, Langkilde, A, Sabatine, M, Bansilal, S, Furtado, R, Fish, M, Gabovitch, D, Jevne, A, Ahern, S, Im, K, Goodrich, E, Lowe, C, Fisher, N, Gannon, J, Trindade, S, Towarowski, A, Fox, Y, Johnsson, E, Ranft, S, Faber, B, Wallander, M, Weiss, A, Buskila, A, Abola, M, Ardissino, D, Averkov, O, Aylward, P, Bode, C, Bonnici, F, Bonora, E, Budaj, A, Cernea, S, Chiang, C, Cooper, M, Dalby, A, Deerochanawong, C, Dellborg, M, Diaz, R, Dimulescu, D, Eliaschewitz, F, Goudev, A, Hadjadj, S, Herrera, M, Huo, Y, Jermendy, G, Ji, L, Kadowaki, T, Kiss, R, Kooy, A, Kumar, K, Lewis, B, Litwak, L, Lopez-Sendon, J, Ma, R, Merlini, P, Nauck, M, Nguyen, T, Nicolau, J, Ostgren, C, Ophuis, T, Padilla, F, Pais, P, Park, K, Parkhomenko, A, Ray, K, Rosenstock, J, Ruda, M, Satman, I, Shestakova, M, Smahelova, A, Spinar, J, Strojek, K, Sy, R, Tankova, T, Theroux, P, Tkac, I, Van Gaal, L, Wainstein, J, Harrington, R, Droller, M, Lee, K, Nesto, R, Tuomilehto, J, Hedlin, H, Desai, M, Sayfer, I, Alexanian, S, Awtry, E, Bentley-Lewis, R, Berger, C, Croce, K, Desai, A, Garg, R, Gelfand, E, Gignac, G, Goessling, W, Ho, C, Hochberg, E, Lane, A, Larrey, D, Leeman, D, Lewis, J, Link, M, Mcdonnell, M, Norden, A, Pande, A, Rosenberg, C, Rost, N, Ruberg, F, Schiff, E, Silverman, S, Singhal, A, Wagner, A, Wolpin, B, Aizenberg, D, Fernandez, M, Sala, J, Maffei, L, Luquez, C, Waitman, J, Rista, L, Nardone, L, Sposetti, G, Cantero, M, Alvarisqueta, A, Montana, O, Cuadrado, J, Cartasegna, L, Baccaro, C, Chertkoff, A, Sanabria, H, Vainstein, N, Amerena, J, Arya, K, D'Emden, M, Proietto, J, Moses, R, Colquhoun, D, Stranks, S, Lehman, R, Hamilton, A, Whelan, A, Simpson, R, Purnell, P, Abhayaratna, W, Hammett, C, Mckeirnan, M, Sullivan, D, Bach, L, Hughes, K, Mathieu, C, Vercammen, C, Scheen, A, Duyck, F, Cools, F, De Wolf, L, Verhaegen, A, Nobels, F, Missault, L, Crenier, L, Thoeng, J, Wollaert, B, Vandenbroucke, M, Borges, J, Turatti, L, Lima, F, dos Santos, F, Kerr Saraiva, J, Pereira, M, Pereira, A, Precoma, D, Filho, G, Reis, G, Maia, L, Bacheva, T, Temelkova-Kurktschiev, T, Maneva, S, Stoyanovska, B, Boshnyashka, R, Stoykova, Y, Georgiev, D, Tagarev, Z, Dimitrova, E, Vitkina, M, Yordanova, L, Temelkova, M, Vasileva, S, Kuneva, T, Zyumbyuleva, M, Daskalova, I, Genadieva, V, Boyanov, L, Farah, G, Lazarova, G, Georgieva, M, Krasteva, S, Slavcheva, A, Yabroudi, N, Veleva, N, Zlateva, A, Damyanova, V, Elenkova, A, Kotselova, T, Genov, K, Lyubenova, L, Temelkova, N, Harizanova, B, Zaharieva, S, Bajaj, H, Goldenberg, R, Aronson, R, Twum-Barima, D, Dumas, R, Kouz, S, Kaiser, S, Ajala, B, Cha, J, Teitelbaum, I, Chouinard, G, Woo, V, Dan Dattani, I, Mazza, G, Gaudet, D, Poirier, P, Conway, J, Dion, D, Mckeough, M, Manyari, D, Harris, S, St-Pierre, B, Yale, J, Landry, D, Gupta, M, Hramiak, I, Lau, D, Degrace, M, Gallo, R, Montigny, M, Dzongowski, P, Liutkus, J, Frechette, A, Gosselin, G, Sabbah, E, Langlois, M, Rabasa-Lhoret, R, Bedard, J, Hart, R, Dowell, A, Pandey, A, O'Keefe, D, Hill, L, Weisnagel, S, Muirhead, N, Zimmermann, R, Galiwango, P, Tobe, S, Priestman, B, Zinman, B, Ma, J, Zhao, X, Wang, C, Zhang, A, Dong, Y, Dong, X, Luo, M, Guo, J, Zheng, Z, Li, Y, Liang, Y, Peng, D, Maderic, D, Spinarova, L, Raclavska, L, Ludka, O, Rihacek, I, Karasova, J, Pelikanova, M, Vlasakova, H, Urbancova, K, Zamrazil, V, Hradec, J, Vlasicova, H, Racicka, E, Okenka, L, Naplava, R, Skopecek, J, Palova, S, Krystl, T, Pistek, Z, Oznerova, M, Andresova, A, Sarbochova, R, Taborska, P, Petrova, I, Stanek, L, Reichert, P, Lorenc, Z, Szabo, M, Petit, C, Krempf, M, Boye, A, Dubois, S, Clavel, S, Gourdy, P, Elbaz, M, Jazayeri, S, Gouet, D, Verges, B, Couffinhal, T, Sendeski, M, Klausmann, G, Appel, K, Pein, M, Thieme, R, Schumm-Draeger, P, Jacob, S, Toursarkissian, N, Kleinecke-Pohl, U, Tschope, D, Ott, P, Haak, T, Derwahl, K, Bugger, H, Hui, G, Tsang, C, Zilahi, Z, Puski, L, Vangel, S, Fulop, T, Pall, K, Hidvegi, T, Revesz, K, Koranyi, L, Kajetan, M, Kerenyi, Z, Penzes, J, Herczeg, B, Laszloczky, A, Turi, T, Rapi, J, Pentek, Z, Gaal, Z, Winkler, G, Percs, E, Czigany, A, Harcsa, E, Gurzo, M, Tassaly, J, Horthy, R, Petro, G, Farago, K, Muller, G, Varju, I, Kirschner, R, Kiss, I, Bakai, J, Kancz, S, Marton, Z, Kodur, R, Yajnik, C, Thomas, N, Ayyar, V, Iyengar, P, Bashkin, A, Daoud, D, Itzhak, B, Katz, A, Tsur, A, Nikolsky, E, Atar, S, Grossman, A, Klainman, E, Tsalihin, D, Shotan, A, Turgeman, Y, Ferrario, M, Piatti, P, Zenari, L, Trevisan, R, Bosco, B, Di Lorenzo, L, Mannucci, E, Avogaro, A, Reimers, B, Trimarco, B, Silvestri, O, Salvioni, A, Nakagawa, H, Sueyoshi, A, Fukuda, K, Yasumoto, H, Matsubayashi, S, Kawajiri, K, Togashi, Y, Senokuchi, T, Ohta, Y, Yamauchi, T, Node, K, Alcocer Gamba, M, Herrera Marmolejo, M, De los Rios Ibarra, M, Gonzalez Galvez, G, Garcia Cantu, E, Leguizamo Dimas, A, Luna Ceballos, R, Medina Pech, C, Stobschinski de Alba, C, Gonzalez Gonzalez, J, Padilla Padilla, F, Fanghanel Salmon, G, Robles Torres, F, Lopez Rosas, E, Pelayo Orozco, E, Banda Elizondo, R, Escalona Caamano, A, Frenk Baron, P, Aguilar Salinas, C, Mustieles Rocha, C, Vidrio Velazquez, M, Rodriguez Briones, I, Saldate Alonso, M, Velasco Sanchez, R, Groenemeijer, B, Ronner, E, Kuijper, A, Strikwerda, S, Van Kempen, W, Gijsbers, S, Oude Ophuis, A, Swart, H, Hoogenberg, K, Hovens, M, van Hessen, M, Westerink, J, Kragten, J, Nierop, P, Bax, W, Hartong, S, Nieuwdorp, M, Gonkel, F, Al Windy, N, Troquay, R, Schaafsma, H, Lieverse, A, Knufman, N, Tirador, L, Guenon, M, Ferrolino, A, Atilano, A, Aportadera, M, Que, M, Denopol, M, Tolentino, M, Jimeno, C, Wee, J, Mirasol, R, Panelo, A, Roxas, D, Palmes, P, Silva, A, Salvador, D, Rosita, R, Maravilla, L, Rogelio, G, Pacheco, E, Tin Hay, L, Prado, J, Krzyzagorska, E, Witek, R, Miklaszewicz, B, Sudnik, W, Pomiecko, W, Bochenek, A, Fares, 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D., Pande A., Rosenberg C., Rost N., Ruberg F., Schiff E., Silverman S., Singhal A., Wagner A., Wolpin B., Aizenberg D., Fernandez M., Sala J., Maffei L., Luquez C., Waitman J., Rista L., Nardone L., Sposetti G., Cantero M., Alvarisqueta A., Montana O., Cuadrado J., Cartasegna L., Baccaro C., Chertkoff A., Sanabria H., Vainstein N., Amerena J., Arya K., d'Emden M., Proietto J., Moses R., Colquhoun D., Stranks S., Lehman R., Hamilton A., Whelan A., Simpson R., Purnell P., Abhayaratna W., Hammett C., McKeirnan M., Sullivan D., Bach L., Hughes K., Mathieu C., Vercammen C., Scheen A., Duyck F., Cools F., De Wolf L., Verhaegen A., Nobels F., Missault L., Crenier L., Thoeng J., Wollaert B., Vandenbroucke M., Eliaschewitz F., Borges J. L. C., Turatti L., Lima F. G., dos Santos F., Kerr Saraiva J., Pereira M., Pereira A., Precoma D. B., Filho G. F. V., Reis G., Maia L. N., Bacheva T., Temelkova-Kurktschiev T., Maneva S., Stoyanovska B., Boshnyashka R., Stoykova Y., Georgiev D., Tagarev Z., Dimitrova E., Vitkina M., Yordanova L., Temelkova M., Vasileva S., Kuneva T., Zyumbyuleva M., Daskalova I., Genadieva V., Boyanov L., Farah G., Lazarova G., Georgieva M., Krasteva S., Slavcheva A., Yabroudi N., Veleva N., Zlateva A., Damyanova V., Elenkova A., Kotselova T., Genov K., Lyubenova L., Temelkova N., Harizanova B., Zaharieva S., Bajaj H., Goldenberg R., Aronson R., Twum-Barima D., Dumas R., Kouz S., Kaiser S. M., Ajala B., Cha J., Teitelbaum I., Chouinard G., Woo V., Dan Dattani I., Mazza G., Gaudet D., Poirier P., Conway J., Dion D., McKeough M., Manyari D., Harris S., St-Pierre B., Yale J. F., Landry D., Gupta M., Hramiak I., Lau D., DeGrace M., Gallo R., Montigny M., Dzongowski P., Liutkus J., Frechette A., Gosselin G., Sabbah E., Langlois M. F., Rabasa-Lhoret R., Bedard J., Hart R., Dowell A., Pandey A., O'Keefe D., Hill L., Weisnagel S. J., Muirhead N., Zimmermann R., Galiwango P., Tobe S., Priestman B., Zinman B., Ma J., Zhao X., Wang C., Zhang A., Dong Y., Dong X., Luo M., Guo J., Zheng Z., Li Y., Liang Y., Peng D., Maderic D., Spinarova L., Raclavska L., Ludka O., Rihacek I., Karasova J., Pelikanova M., Vlasakova H., Urbancova K., Zamrazil V., Hradec J., Vlasicova H., Racicka E., Okenka L., Naplava R., Skopecek J., Palova S., Krystl T., Pistek Z., Oznerova M., Andresova A., Sarbochova R., Taborska P., Petrova I., Stanek L., Reichert P., Lorenc Z., Szabo M., Petit C., Krempf M., Boye A., Dubois S., Clavel S., Gourdy P., Elbaz M., Jazayeri S., Gouet D., Verges B., Couffinhal T., Sendeski M., Klausmann G., Appel K., Pein M., Thieme R., Schumm-Draeger P., Jacob S., Toursarkissian N., Kleinecke-Pohl U., Tschope D., Ott P., Haak T., Nauck M., Derwahl K., Bugger H., Hui G., Tsang C., Zilahi Z., Puski L., Vangel S., Fulop T., Pall K., Hidvegi T., Revesz K., Koranyi L., Kajetan M., Kerenyi Z., Penzes J., Herczeg B., Laszloczky A., Turi T., Rapi J., Pentek Z., Gaal Z., Winkler G., Percs E., Czigany A., Harcsa E., Gurzo M., Tassaly J., Horthy R., Petro G., Farago K., Muller G., Varju I., Kirschner R., Kiss I., Bakai J., Kancz S., Marton Z., Kodur R., Yajnik C., Thomas N., Ayyar V., Iyengar P., Bashkin A., Daoud D., Itzhak B., Katz A., Tsur A., Nikolsky E., Atar S., Grossman A., Klainman E., Tsalihin D., Shotan A., Turgeman Y., Ferrario M., Merlini P., Piatti P., Zenari L., Trevisan R., Bosco B., Di Lorenzo L., Mannucci E., Avogaro A., Reimers B., Trimarco B., Silvestri O., Salvioni A., Nakagawa H., Sueyoshi A., Fukuda K., Yasumoto H., Matsubayashi S., Kawajiri K., Togashi Y., Senokuchi T., Ohta Y., Yamauchi T., Node K., Alcocer Gamba M., Herrera Marmolejo M., De los Rios Ibarra M., Gonzalez Galvez G., Garcia Cantu E., Leguizamo Dimas A., Luna Ceballos R., Medina Pech C., Stobschinski de Alba C., Gonzalez Gonzalez J., Padilla Padilla F., Fanghanel Salmon G., Robles Torres F., Lopez Rosas E., Pelayo Orozco E., Banda Elizondo R., Escalona Caamano A., Frenk Baron P., Aguilar Salinas C., Mustieles Rocha C., Vidrio Velazquez M., Rodriguez Briones I., Saldate Alonso M., Velasco Sanchez R., Groenemeijer B., Ronner E., Kuijper A., Strikwerda S., Van Kempen W., Gijsbers S., Oude Ophuis A., Swart H., Hoogenberg K., Hovens M., van Hessen M., Westerink J., Kragten J., Nierop P., Bax W., Hartong S., Nieuwdorp M., Gonkel F., Al Windy N., Troquay R., Schaafsma H., Lieverse A., Knufman N., Tirador L., Guenon M., Ferrolino A., Atilano A., Aportadera M., Que M., Denopol M., Tolentino M., Jimeno C., Wee J., Mirasol R., Panelo A., Roxas D., Abola M., Palmes P., Silva A., Salvador D., Rosita R., Maravilla L., Rogelio G., Pacheco E., Tin Hay L., Prado J., Krzyzagorska E., Witek R., Miklaszewicz B., Sudnik W., Pomiecko W., Bochenek A., Fares I., Wujkowski M., Korol M., Powierza S., Goch A., Miekus P., Siegel A., Skierkowska J., Romanczuk P., Cygler J., Landa K., Szyprowska E., Stachlewski P., Czerski T., Pawlowicz L., Sowinski D., Romanowski L., Rudzki H., Skorski M., Jasiel-Wojculewicz H., Stasiewski A., Budaj A., Kania G., Mirek-Bryniarska E., Wojnowski L., Korzeniak R., Oh T., Park K., Lee M., Lee K., Jang H., Kim S., Ku B., Cha B., Son H., Lee I., Park J., Yu S., Shon H., Rhee E., Cho J., Park T., Nam J., Pintilei E., Popescu A., Nafornita V., Gutu O., Dumitrescu A., Bala C., Caceaune E., Mindrescu N., Morosanu M., Bradescu O., Munteanu M., Voitec M., Vlaiculescu M., Hancu N., Diaconu Sotropa M., Lupu S., Mateescu A., Carlan L., Marton R., Lupusoru D., Mot A., Coman A., Zaharie D., Rebrov A., Shutemova E., Bolieva L., Khalimov Y., Statsenko M., Galyavich A., Koziolova N., Shapovalova Y., Pavlysh E., Strongin L., Vertkin A., Vishneva E., Pavlova M., Khasanov N., Antsiferov M., Gavrisheva I., Sokolova N., Vorobyev S., Morugova T., Sinitsina I., Ezhov A., Kobalava Z., Belenkiy D., Supryadkina T., Kazakov Y., Oschepkova E., Dreval A., Novikova T., Vishnevsky A., Chizhov D., Akatova E., Vorokhobina N., Ivanov I., Dudinskaya E., Konstantinov V., Kanderkova D., Pavlik L., Raslova K., Paulovic V., Babikova J., Belesova K., Merciakova M., Truban J., Vargova A., Fabryova L., Slovenska M., Plasil R., Tomasova L., Kollarova D., Spodniakova D., Kosikova M., Dzuponova J., Kurcova I., Skripova D., Gabrisova A., Kalinova S., Ranjith N., Burgess L., Mitha I., Conradie M., Distiller L., Pillai P., Pillay S., Horak A., Nethononda R., van den Berg E., Nortje H., Bayat J., Corbett C., Abelson M., van Zyl L., Pillay T., Wing J., Kapp C., Hidalgo Urbano R., Gonzalez Juanatey J., Blanco Coronado J., Bruguera Cortada J., Ferreiro Gutierrez J., Quesada Simon M., Castro A., Delgado Alvarez E., Freixa R., Boada A., Larnefeldt H., Mooe T., Koskinen P., Lagerback P., Linderfalk C., Liu B., Berndtsson Blom K., Tengmark B., Lindholm C., Ostgren C., Oweling M., Albertsson P., Alvarsson M., Fant S., Berglund O., Hsia C., Chiang C., Fang C., Ueng K., Wang K., Lai W., Mamanasiri S., Wongvipaporn C., Kuanprasert S., Thongsri T., Srimahachota S., Boonyavarakul A., Suwanwalaikorn S., Tantiwong P., Sritara P., Sriwijitkamol A., Sanguanwong S., Chotinaiwattarakul C., Piyayotai D., Balci M., Orbay E., Saygili F., Oguz A., Altuntas Y., Comlekci A., Karpenko O., Tkach S., Vlasenko M., Fushtey I., Pertseva T., Reshotko D., Mostovoy Y., Vizir V., Kraiz I., Amosova K., Batushkin V., Tseluyko V., Koval O., Strang C., Bodalia B., Pieters R., Turner W., Asamoah-Owusu N., White C., Calvert J., McNally D., Jones N., McKaig G., Thompson J., Mohr S., Simpson H., Conn P., McCoye A., Rivero O., Yazdani S., Ince C., Zeitlin J., Wharton T., Platt G., Anderson R. J., Angueira-Serrano E., Lillestol M., Hanlon B., Soufer J., Garcia B., Iteld B., Venugopal C., Ahmed A., Duardo-Guerra Y., Jetty P., Miranda A., Wahlen J., Lederman S., Cohen K., Lake L., French W. J., Tahirkheli N., Baker S., Stoltz R., Wilson J., Nadar V., Brown J., Larrain G., Wiseman A., Ruoff G., Williams M., Tan A., Hartman I., Singh N., Graf R., Wakefield P., McNeill R., Byars W., Reyes Almodovar R., Jones S., Kantaros L., Hegedosh N., Graves M., Bernstein M., Falkowski S., Bialow M., Paraschos A., Dagher G., Arif A., Condit J., Chaykin L., Grunstra B., Earl J., Unks D., Srivastava S., Benson M., Huffman C., Miller G., Willis J., Bender K., Martin E., Blackmore R., Rohr K., Chilka S., Gadowski G., Fitz-Patrick D., Benjamin S., Morin D., Zias Dilena A., Acosta R., Claassen D., Miranda F., Raad G., Inzerello A., Porter J., Bhattacharya A., Gutmann J., Korpas D., Syed M., Zieve F., Raisinghani A., Alam S., Bartkowiak A., Boccalandro F., Talano J., Mercado A., Krichmar P., Oldfield C., Adams K., Gorman T., Lewis D., Shah R., Shockey G., Lefebvre G., Andrawis N., Tami L., Bittar N., Khan M. S., Rink L., Hendrix E., Wood J., Robinson J., Pavon H., Irfan M., Gonzalez E., Singal R., Shore K., Saba F., Bianco J., Erickson B., Gorson D., Puri S., Arauz-Pacheco C., Forman S., Akyea-Djamson A., Lieber I., Barker B., Desai P., Sotolongo C., Steinhoff J., Hill R., Radin M., Patel R., Lieberman S., Wenocur H., Dagogo-Jack S., Lupovitch S., Ison R., Bacharach J. M., Diogo J., Mazzella M., Greenwald J., Quadrel M., Mayer N., Datu J., McCartney M., Bruce T., Singal D., Turner J., Videau B., Fritz R., Fox D., Calatayud G., Sheldon W., Kereiakes D., Thomas J., Salacata A., McCullum K., Harris B., de Souza J., Rahman A., Blumenthal S., Narayan P., Bloch M., Augenbraun C., Bernstein R., Perlman R., Berman J., LaBryer L., Wynne A., Fish J., Zarich S., Gabra N., Popeil L., Hermany P., Barreto A., Pomposini D., Gonzalez-Campoy J. M., Langer M., Bayron C., Suneja R., Kamlet J., Wheeler K., Hurley S., Sharma S., Wefald F., Hershon K., O'Connor T., Pueblitz G., Laguerre J., Amin M., Alfonso T., Jaffrani N., Isserman S., Portnay E., Vlastaris A., Dy J., Hagan M., Noveck H., Kraft P., Andersen J., Foley B., Carr K., Gelormini J., Williams T., Landau C., Richwine R., Thakkar M., Karim A., Madhun Z., Francyk D., Lamantia J., Baker B., Zhang W., Lev V., Hasan M., Captain A., Herzog W., Friedman K., Lawson W., Desai V., Ow C., Simons R., Mandviwala M., Le T., Hack T., Zebrack J., Henderson D., DeJulia J., Mehta R., Reza S., Poonawala R., Awad A., Velasquez M., Mohiuddin S., Salazar Sharma M., Myrick G., Gottlieb D., Ovalle F., Alfieri A., Ahmed S., Bohula E., Donahoe S. M., Longshaw K., Eshaghian S., Lash J., Goldberg R. K., Fox B., Mostel E., Dobies D., Ward H., Burbano J., Puleo P., Lenhard M. J., Korn D., Thadani U., Bradley A., Kmetzo J., Heasley E., Raikhel M., Mahr N., Bittar G., Fuentes F., Raghu P., Diep T. T. B., Tran Q. K., Tran N., Nguyen D., and Nguyen V.

Abstract

BACKGROUND The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. METHODS We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to ≥60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. RESULTS We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], ≥1.3; P≥0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P = 0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P = 0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87)

Published
2019

39. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes

Author

Wiviott S. D., Raz I., Bonaca M. P., Mosenzon O., Kato E. T., Cahn A., Silverman M. G., Zelniker T. A., Kuder J. F., Murphy S. A., Bhatt D. L., Leiter L. A., McGuire D. K., Wilding J. P. H., Ruff C. T., Nilsson G. I., Fredriksson M., Johansson P. A., Langkilde A. M., Sabatine M. S., Bansilal S., Furtado R., Fish M. P., Gabovitch D., Jevne A., Ahern S., Im K., Goodrich E. L., Lowe C., Fisher N., Gannon J., Trindade S., Towarowski A., Fox Y., Johnsson E., Ranft S., Faber B., Wallander M., Weiss A., Buskila A., Abola M. T. B., Ardissino D., Averkov O., Aylward P., Bode C., Bonnici F., Bonora E., Budaj A. J., Cernea S., Chiang C. E., Cooper M., Dalby A., Deerochanawong C., Dellborg M., Diaz R., Dimulescu D., Eliaschewitz F. G., Goudev A. R., Hadjadj S., Herrera M., Huo Y., Jermendy G., Ji L., Kadowaki T., Kiss R., Kooy A., Kumar K. M. P., Lewis B., Litwak L., Lopez-Sendon J., Ma R., Merlini P. A., Nauck M. A., Nguyen T. K., Nicolau J. C., Ostgren C. J., Ophuis T. O., Padilla F., Pais P., Park K. S., Parkhomenko A., Ray K., Rosenstock J., Ruda M., Satman I., Shestakova M., Smahelova A., Spinar J., Strojek K., Sy R., Tankova T., Theroux P., Tkac I., Van Gaal L., Wainstein J., Harrington R. A., Droller M. J., Lee K. L., Nesto R. W., Tuomilehto J., Hedlin H., Desai M., Sayfer I., Alexanian S., Awtry E., Bentley-Lewis R., Berger C. J., Croce K., Desai A., Garg R. K., Gelfand E., Gignac G., Goessling W., Ho C., Hochberg E., Lane A., Larrey D., Leeman D. E., Lewis J., Link M. S., McDonnell M. E., Norden A. D., Pande A., Rosenberg C., Rost N., Ruberg F., Schiff E., Silverman S., Singhal A., Wagner A., Wolpin B., Aizenberg D., Fernandez M., Sala J., Maffei L., Luquez C., Waitman J., Rista L., Nardone L., Sposetti G., Cantero M., Alvarisqueta A., Montana O., Cuadrado J., Cartasegna L., Baccaro C., Chertkoff A., Sanabria H., Vainstein N., Amerena J., Arya K., d'Emden M., Proietto J., Moses R., Colquhoun D., Stranks S., Lehman R., Hamilton A., Whelan A., Simpson R., Purnell P., Abhayaratna W., Hammett C., McKeirnan M., Sullivan D., Bach L., Hughes K., Mathieu C., Vercammen C., Scheen A., Duyck F., Cools F., De Wolf L., Verhaegen A., Nobels F., Missault L., Crenier L., Thoeng J., Wollaert B., Vandenbroucke M., Eliaschewitz F., Borges J. L. C., Turatti L., Lima F. G., dos Santos F., Kerr Saraiva J., Pereira M., Pereira A., Precoma D. B., Filho G. F. V., Reis G., Maia L. N., Bacheva T., Temelkova-Kurktschiev T., Maneva S., Stoyanovska B., Boshnyashka R., Stoykova Y., Georgiev D., Tagarev Z., Dimitrova E., Vitkina M., Yordanova L., Temelkova M., Vasileva S., Kuneva T., Zyumbyuleva M., Daskalova I., Genadieva V., Boyanov L., Farah G., Lazarova G., Georgieva M., Krasteva S., Slavcheva A., Yabroudi N., Veleva N., Zlateva A., Damyanova V., Elenkova A., Kotselova T., Genov K., Lyubenova L., Temelkova N., Harizanova B., Zaharieva S., Bajaj H., Goldenberg R., Aronson R., Twum-Barima D., Dumas R., Kouz S., Kaiser S. M., Ajala B., Cha J., Teitelbaum I., Chouinard G., Woo V., Dan Dattani I., Mazza G., Gaudet D., Poirier P., Conway J., Dion D., McKeough M., Manyari D., Harris S., St-Pierre B., Yale J. F., Landry D., Gupta M., Hramiak I., Lau D., DeGrace M., Gallo R., Montigny M., Dzongowski P., Liutkus J., Frechette A., Gosselin G., Sabbah E., Langlois M. F., Rabasa-Lhoret R., Bedard J., Hart R., Dowell A., Pandey A., O'Keefe D., Hill L., Weisnagel S. J., Muirhead N., Zimmermann R., Galiwango P., Tobe S., Priestman B., Zinman B., Ma J., Zhao X., Wang C., Zhang A., Dong Y., Dong X., Luo M., Guo J., Zheng Z., Li Y., Liang Y., Peng D., Maderic D., Spinarova L., Raclavska L., Ludka O., Rihacek I., Karasova J., Pelikanova M., Vlasakova H., Urbancova K., Zamrazil V., Hradec J., Vlasicova H., Racicka E., Okenka L., Naplava R., Skopecek J., Palova S., Krystl T., Pistek Z., Oznerova M., Andresova A., Sarbochova R., Taborska P., Petrova I., Stanek L., Reichert P., Lorenc Z., Szabo M., Petit C., Krempf M., Boye A., Dubois S., Clavel S., Gourdy P., Elbaz M., Jazayeri S., Gouet D., Verges B., Couffinhal T., Sendeski M., Klausmann G., Appel K., Pein M., Thieme R., Schumm-Draeger P., Jacob S., Toursarkissian N., Kleinecke-Pohl U., Tschope D., Ott P., Haak T., Nauck M., Derwahl K., Bugger H., Hui G., Tsang C., Zilahi Z., Puski L., Vangel S., Fulop T., Pall K., Hidvegi T., Revesz K., Koranyi L., Kajetan M., Kerenyi Z., Penzes J., Herczeg B., Laszloczky A., Turi T., Rapi J., Pentek Z., Gaal Z., Winkler G., Percs E., Czigany A., Harcsa E., Gurzo M., Tassaly J., Horthy R., Petro G., Farago K., Muller G., Varju I., Kirschner R., Kiss I., Bakai J., Kancz S., Marton Z., Kodur R., Yajnik C., Thomas N., Ayyar V., Iyengar P., Bashkin A., Daoud D., Itzhak B., Katz A., Tsur A., Nikolsky E., Atar S., Grossman A., Klainman E., Tsalihin D., Shotan A., Turgeman Y., Ferrario M., Merlini P., Piatti P., Zenari L., Trevisan R., Bosco B., Di Lorenzo L., Mannucci E., Avogaro A., Reimers B., Trimarco B., Silvestri O., Salvioni A., Nakagawa H., Sueyoshi A., Fukuda K., Yasumoto H., Matsubayashi S., Kawajiri K., Togashi Y., Senokuchi T., Ohta Y., Yamauchi T., Node K., Alcocer Gamba M., Herrera Marmolejo M., De los Rios Ibarra M., Gonzalez Galvez G., Garcia Cantu E., Leguizamo Dimas A., Luna Ceballos R., Medina Pech C., Stobschinski de Alba C., Gonzalez Gonzalez J., Padilla Padilla F., Fanghanel Salmon G., Robles Torres F., Lopez Rosas E., Pelayo Orozco E., Banda Elizondo R., Escalona Caamano A., Frenk Baron P., Aguilar Salinas C., Mustieles Rocha C., Vidrio Velazquez M., Rodriguez Briones I., Saldate Alonso M., Velasco Sanchez R., Groenemeijer B., Ronner E., Kuijper A., Strikwerda S., Van Kempen W., Gijsbers S., Oude Ophuis A., Swart H., Hoogenberg K., Hovens M., van Hessen M., Westerink J., Kragten J., Nierop P., Bax W., Hartong S., Nieuwdorp M., Gonkel F., Al Windy N., Troquay R., Schaafsma H., Lieverse A., Knufman N., Tirador L., Guenon M., Ferrolino A., Atilano A., Aportadera M., Que M., Denopol M., Tolentino M., Jimeno C., Wee J., Mirasol R., Panelo A., Roxas D., Abola M., Palmes P., Silva A., Salvador D., Rosita R., Maravilla L., Rogelio G., Pacheco E., Tin Hay L., Prado J., Krzyzagorska E., Witek R., Miklaszewicz B., Sudnik W., Pomiecko W., Bochenek A., Fares I., Wujkowski M., Korol M., Powierza S., Goch A., Miekus P., Siegel A., Skierkowska J., Romanczuk P., Cygler J., Landa K., Szyprowska E., Stachlewski P., Czerski T., Pawlowicz L., Sowinski D., Romanowski L., Rudzki H., Skorski M., Jasiel-Wojculewicz H., Stasiewski A., Budaj A., Kania G., Mirek-Bryniarska E., Wojnowski L., Korzeniak R., Oh T., Park K., Lee M., Lee K., Jang H., Kim S., Ku B., Cha B., Son H., Lee I., Park J., Yu S., Shon H., Rhee E., Cho J., Park T., Nam J., Pintilei E., Popescu A., Nafornita V., Gutu O., Dumitrescu A., Bala C., Caceaune E., Mindrescu N., Morosanu M., Bradescu O., Munteanu M., Voitec M., Vlaiculescu M., Hancu N., Diaconu Sotropa M., Lupu S., Mateescu A., Carlan L., Marton R., Lupusoru D., Mot A., Coman A., Zaharie D., Rebrov A., Shutemova E., Bolieva L., Khalimov Y., Statsenko M., Galyavich A., Koziolova N., Shapovalova Y., Pavlysh E., Strongin L., Vertkin A., Vishneva E., Pavlova M., Khasanov N., Antsiferov M., Gavrisheva I., Sokolova N., Vorobyev S., Morugova T., Sinitsina I., Ezhov A., Kobalava Z., Belenkiy D., Supryadkina T., Kazakov Y., Oschepkova E., Dreval A., Novikova T., Vishnevsky A., Chizhov D., Akatova E., Vorokhobina N., Ivanov I., Dudinskaya E., Konstantinov V., Kanderkova D., Pavlik L., Raslova K., Paulovic V., Babikova J., Belesova K., Merciakova M., Truban J., Vargova A., Fabryova L., Slovenska M., Plasil R., Tomasova L., Kollarova D., Spodniakova D., Kosikova M., Dzuponova J., Kurcova I., Skripova D., Gabrisova A., Kalinova S., Ranjith N., Burgess L., Mitha I., Conradie M., Distiller L., Pillai P., Pillay S., Horak A., Nethononda R., van den Berg E., Nortje H., Bayat J., Corbett C., Abelson M., van Zyl L., Pillay T., Wing J., Kapp C., Hidalgo Urbano R., Gonzalez Juanatey J., Blanco Coronado J., Bruguera Cortada J., Ferreiro Gutierrez J., Quesada Simon M., Castro A., Delgado Alvarez E., Freixa R., Boada A., Larnefeldt H., Mooe T., Koskinen P., Lagerback P., Linderfalk C., Liu B., Berndtsson Blom K., Tengmark B., Lindholm C., Ostgren C., Oweling M., Albertsson P., Alvarsson M., Fant S., Berglund O., Hsia C., Chiang C., Fang C., Ueng K., Wang K., Lai W., Mamanasiri S., Wongvipaporn C., Kuanprasert S., Thongsri T., Srimahachota S., Boonyavarakul A., Suwanwalaikorn S., Tantiwong P., Sritara P., Sriwijitkamol A., Sanguanwong S., Chotinaiwattarakul C., Piyayotai D., Balci M., Orbay E., Saygili F., Oguz A., Altuntas Y., Comlekci A., Karpenko O., Tkach S., Vlasenko M., Fushtey I., Pertseva T., Reshotko D., Mostovoy Y., Vizir V., Kraiz I., Amosova K., Batushkin V., Tseluyko V., Koval O., Strang C., Bodalia B., Pieters R., Turner W., Asamoah-Owusu N., White C., Calvert J., McNally D., Jones N., McKaig G., Thompson J., Mohr S., Simpson H., Conn P., McCoye A., Rivero O., Yazdani S., Ince C., Zeitlin J., Wharton T., Platt G., Anderson R. J., Angueira-Serrano E., Lillestol M., Hanlon B., Soufer J., Garcia B., Iteld B., Venugopal C., Ahmed A., Duardo-Guerra Y., Jetty P., Miranda A., Wahlen J., Lederman S., Cohen K., Lake L., French W. J., Tahirkheli N., Baker S., Stoltz R., Wilson J., Nadar V., Brown J., Larrain G., Wiseman A., Ruoff G., Williams M., Tan A., Hartman I., Singh N., Graf R., Wakefield P., McNeill R., Byars W., Reyes Almodovar R., Jones S., Kantaros L., Hegedosh N., Graves M., Bernstein M., Falkowski S., Bialow M., Paraschos A., Dagher G., Arif A., Condit J., Chaykin L., Grunstra B., Earl J., Unks D., Srivastava S., Benson M., Huffman C., Miller G., Willis J., Bender K., Martin E., Blackmore R., Rohr K., Chilka S., Gadowski G., Fitz-Patrick D., Benjamin S., Morin D., Zias Dilena A., Acosta R., Claassen D., Miranda F., Raad G., Inzerello A., Porter J., Bhattacharya A., Gutmann J., Korpas D., Syed M., Zieve F., Raisinghani A., Alam S., Bartkowiak A., Boccalandro F., Talano J., Mercado A., Krichmar P., Oldfield C., Adams K., Gorman T., Lewis D., Shah R., Shockey G., Lefebvre G., Andrawis N., Tami L., Bittar N., Khan M. S., Rink L., Hendrix E., Wood J., Robinson J., Pavon H., Irfan M., Gonzalez E., Singal R., Shore K., Saba F., Bianco J., Erickson B., Gorson D., Puri S., Arauz-Pacheco C., Forman S., Akyea-Djamson A., Lieber I., Barker B., Desai P., Sotolongo C., Steinhoff J., Hill R., Radin M., Patel R., Lieberman S., Wenocur H., Dagogo-Jack S., Lupovitch S., Ison R., Bacharach J. M., Diogo J., Mazzella M., Greenwald J., Quadrel M., Mayer N., Datu J., McCartney M., Bruce T., Singal D., Turner J., Videau B., Fritz R., Fox D., Calatayud G., Sheldon W., Kereiakes D., Thomas J., Salacata A., McCullum K., Harris B., de Souza J., Rahman A., Blumenthal S., Narayan P., Bloch M., Augenbraun C., Bernstein R., Perlman R., Berman J., LaBryer L., Wynne A., Fish J., Zarich S., Gabra N., Popeil L., Hermany P., Barreto A., Pomposini D., Gonzalez-Campoy J. M., Langer M., Bayron C., Suneja R., Kamlet J., Wheeler K., Hurley S., Sharma S., Wefald F., Hershon K., O'Connor T., Pueblitz G., Laguerre J., Amin M., Alfonso T., Jaffrani N., Isserman S., Portnay E., Vlastaris A., Dy J., Hagan M., Noveck H., Kraft P., Andersen J., Foley B., Carr K., Gelormini J., Williams T., Landau C., Richwine R., Thakkar M., Karim A., Madhun Z., Francyk D., Lamantia J., Baker B., Zhang W., Lev V., Hasan M., Captain A., Herzog W., Friedman K., Lawson W., Desai V., Ow C., Simons R., Mandviwala M., Le T., Hack T., Zebrack J., Henderson D., DeJulia J., Mehta R., Reza S., Poonawala R., Awad A., Velasquez M., Mohiuddin S., Salazar Sharma M., Myrick G., Gottlieb D., Ovalle F., Alfieri A., Ahmed S., Bohula E., Donahoe S. M., Longshaw K., Eshaghian S., Lash J., Goldberg R. K., Fox B., Mostel E., Dobies D., Ward H., Burbano J., Puleo P., Lenhard M. J., Korn D., Thadani U., Bradley A., Kmetzo J., Heasley E., Raikhel M., Mahr N., Bittar G., Fuentes F., Raghu P., Diep T. T. B., Tran Q. K., Tran N., Nguyen D., Nguyen V., Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), VA Boston Healthcare System, Turbulence Research Laboratory [Goteborg], Chalmers University of Technology [Göteborg], Wiviott, S, Raz, I, Bonaca, M, Mosenzon, O, Kato, E, Cahn, A, Silverman, M, Zelniker, T, Kuder, J, Murphy, S, Bhatt, D, Leiter, L, Mcguire, D, Wilding, J, Ruff, C, Nilsson, G, Fredriksson, M, Johansson, P, Langkilde, A, Sabatine, M, Bansilal, S, Furtado, R, Fish, M, Gabovitch, D, Jevne, A, Ahern, S, Im, K, Goodrich, E, Lowe, C, Fisher, N, Gannon, J, Trindade, S, Towarowski, A, Fox, Y, Johnsson, E, Ranft, S, Faber, B, Wallander, M, Weiss, A, Buskila, A, Abola, M, Ardissino, D, Averkov, O, Aylward, P, Bode, C, Bonnici, F, Bonora, E, Budaj, A, Cernea, S, Chiang, C, Cooper, M, Dalby, A, Deerochanawong, C, Dellborg, M, Diaz, R, Dimulescu, D, Eliaschewitz, F, Goudev, A, Hadjadj, S, Herrera, M, Huo, Y, Jermendy, G, Ji, L, Kadowaki, T, Kiss, R, Kooy, A, Kumar, K, Lewis, B, Litwak, L, Lopez-Sendon, J, Ma, R, Merlini, P, Nauck, M, Nguyen, T, Nicolau, J, Ostgren, C, Ophuis, T, Padilla, F, Pais, P, Park, K, Parkhomenko, A, Ray, K, Rosenstock, J, Ruda, M, Satman, I, Shestakova, M, Smahelova, A, Spinar, J, Strojek, K, Sy, R, Tankova, T, Theroux, P, Tkac, I, Van Gaal, L, Wainstein, J, Harrington, R, Droller, M, Lee, K, Nesto, R, Tuomilehto, J, Hedlin, H, Desai, M, Sayfer, I, Alexanian, S, Awtry, E, Bentley-Lewis, R, Berger, C, Croce, K, Desai, A, Garg, R, Gelfand, E, Gignac, G, Goessling, W, Ho, C, Hochberg, E, Lane, A, Larrey, D, Leeman, D, Lewis, J, Link, M, Mcdonnell, M, Norden, A, Pande, A, Rosenberg, C, Rost, N, Ruberg, F, Schiff, E, Silverman, S, Singhal, A, Wagner, A, Wolpin, B, Aizenberg, D, Fernandez, M, Sala, J, Maffei, L, Luquez, C, Waitman, J, Rista, L, Nardone, L, Sposetti, G, Cantero, M, Alvarisqueta, A, Montana, O, Cuadrado, J, Cartasegna, L, Baccaro, C, Chertkoff, A, Sanabria, H, Vainstein, N, Amerena, J, Arya, K, D'Emden, M, Proietto, J, Moses, R, Colquhoun, D, Stranks, S, Lehman, R, Hamilton, A, Whelan, A, Simpson, R, Purnell, P, Abhayaratna, W, Hammett, C, Mckeirnan, M, Sullivan, D, Bach, L, Hughes, K, Mathieu, C, Vercammen, C, Scheen, A, Duyck, F, Cools, F, De Wolf, L, Verhaegen, A, Nobels, F, Missault, L, Crenier, L, Thoeng, J, Wollaert, B, Vandenbroucke, M, Borges, J, Turatti, L, Lima, F, dos Santos, F, Kerr Saraiva, J, Pereira, M, Pereira, A, Precoma, D, Filho, G, Reis, G, Maia, L, Bacheva, T, Temelkova-Kurktschiev, T, Maneva, S, Stoyanovska, B, Boshnyashka, R, Stoykova, Y, Georgiev, D, Tagarev, Z, Dimitrova, E, Vitkina, M, Yordanova, L, Temelkova, M, Vasileva, S, Kuneva, T, Zyumbyuleva, M, Daskalova, I, Genadieva, V, Boyanov, L, Farah, G, Lazarova, G, Georgieva, M, Krasteva, S, Slavcheva, A, Yabroudi, N, Veleva, N, Zlateva, A, Damyanova, V, Elenkova, A, Kotselova, T, Genov, K, Lyubenova, L, Temelkova, N, Harizanova, B, Zaharieva, S, Bajaj, H, Goldenberg, R, Aronson, R, Twum-Barima, D, Dumas, R, Kouz, S, Kaiser, S, Ajala, B, Cha, J, Teitelbaum, I, Chouinard, G, Woo, V, Dan Dattani, I, Mazza, G, Gaudet, D, Poirier, P, Conway, J, Dion, D, Mckeough, M, Manyari, D, Harris, S, St-Pierre, B, Yale, J, Landry, D, Gupta, M, Hramiak, I, Lau, D, Degrace, M, Gallo, R, Montigny, M, Dzongowski, P, Liutkus, J, Frechette, A, Gosselin, G, Sabbah, E, Langlois, M, Rabasa-Lhoret, R, Bedard, J, Hart, R, Dowell, A, Pandey, A, O'Keefe, D, Hill, L, Weisnagel, S, Muirhead, N, Zimmermann, R, Galiwango, P, Tobe, S, Priestman, B, Zinman, B, Ma, J, Zhao, X, Wang, C, Zhang, A, Dong, Y, Dong, X, Luo, M, Guo, J, Zheng, Z, Li, Y, Liang, Y, Peng, D, Maderic, D, Spinarova, L, Raclavska, L, Ludka, O, Rihacek, I, Karasova, J, Pelikanova, M, Vlasakova, H, Urbancova, K, Zamrazil, V, Hradec, J, Vlasicova, H, Racicka, E, Okenka, L, Naplava, R, Skopecek, J, Palova, S, Krystl, T, Pistek, Z, Oznerova, M, Andresova, A, Sarbochova, R, Taborska, P, Petrova, I, Stanek, L, Reichert, P, Lorenc, Z, Szabo, M, Petit, C, Krempf, M, Boye, A, Dubois, S, Clavel, S, Gourdy, P, Elbaz, M, Jazayeri, S, Gouet, D, Verges, B, Couffinhal, T, Sendeski, M, Klausmann, G, Appel, K, Pein, M, Thieme, R, Schumm-Draeger, P, Jacob, S, Toursarkissian, N, Kleinecke-Pohl, U, Tschope, D, Ott, P, Haak, T, Derwahl, K, Bugger, H, Hui, G, Tsang, C, Zilahi, Z, Puski, L, Vangel, S, Fulop, T, Pall, K, Hidvegi, T, Revesz, K, Koranyi, L, Kajetan, M, Kerenyi, Z, Penzes, J, Herczeg, B, Laszloczky, A, Turi, T, Rapi, J, Pentek, Z, Gaal, Z, Winkler, G, Percs, E, Czigany, A, Harcsa, E, Gurzo, M, Tassaly, J, Horthy, R, Petro, G, Farago, K, Muller, G, Varju, I, Kirschner, R, Kiss, I, Bakai, J, Kancz, S, Marton, Z, Kodur, R, Yajnik, C, Thomas, N, Ayyar, V, Iyengar, P, Bashkin, A, Daoud, D, Itzhak, B, Katz, A, Tsur, A, Nikolsky, E, Atar, S, Grossman, A, Klainman, E, Tsalihin, D, Shotan, A, Turgeman, Y, Ferrario, M, Piatti, P, Zenari, L, Trevisan, R, Bosco, B, Di Lorenzo, L, Mannucci, E, Avogaro, A, Reimers, B, Trimarco, B, Silvestri, O, Salvioni, A, Nakagawa, H, Sueyoshi, A, Fukuda, K, Yasumoto, H, Matsubayashi, S, Kawajiri, K, Togashi, Y, Senokuchi, T, Ohta, Y, Yamauchi, T, Node, K, Alcocer Gamba, M, Herrera Marmolejo, M, De los Rios Ibarra, M, Gonzalez Galvez, G, Garcia Cantu, E, Leguizamo Dimas, A, Luna Ceballos, R, Medina Pech, C, Stobschinski de Alba, C, Gonzalez Gonzalez, J, Padilla Padilla, F, Fanghanel Salmon, G, Robles Torres, F, Lopez Rosas, E, Pelayo Orozco, E, Banda Elizondo, R, Escalona Caamano, A, Frenk Baron, P, Aguilar Salinas, C, Mustieles Rocha, C, Vidrio Velazquez, M, Rodriguez Briones, I, Saldate Alonso, M, Velasco Sanchez, R, Groenemeijer, B, Ronner, E, Kuijper, A, Strikwerda, S, Van Kempen, W, Gijsbers, S, Oude Ophuis, A, Swart, H, Hoogenberg, K, Hovens, M, van Hessen, M, Westerink, J, Kragten, J, Nierop, P, Bax, W, Hartong, S, Nieuwdorp, M, Gonkel, F, Al Windy, N, Troquay, R, Schaafsma, H, Lieverse, A, Knufman, N, Tirador, L, Guenon, M, Ferrolino, A, Atilano, A, Aportadera, M, Que, M, Denopol, M, Tolentino, M, Jimeno, C, Wee, J, Mirasol, R, Panelo, A, Roxas, D, Palmes, P, Silva, A, Salvador, D, Rosita, R, Maravilla, L, Rogelio, G, Pacheco, E, Tin Hay, L, Prado, J, Krzyzagorska, E, Witek, R, Miklaszewicz, B, Sudnik, W, Pomiecko, W, Bochenek, A, Fares, I, Wujkowski, M, Korol, M, Powierza, S, Goch, A, Miekus, P, Siegel, A, Skierkowska, J, Romanczuk, P, Cygler, J, Landa, K, Szyprowska, E, Stachlewski, P, Czerski, T, Pawlowicz, L, Sowinski, D, Romanowski, L, Rudzki, H, Skorski, M, Jasiel-Wojculewicz, H, Stasiewski, A, Kania, G, Mirek-Bryniarska, E, Wojnowski, L, Korzeniak, R, Oh, T, Lee, M, Jang, H, Kim, S, Ku, B, Cha, B, Son, H, Lee, I, Park, J, Yu, S, Shon, H, Rhee, E, Cho, J, Park, T, Nam, J, Pintilei, E, Popescu, A, Nafornita, V, Gutu, O, Dumitrescu, A, Bala, C, Caceaune, E, Mindrescu, N, Morosanu, M, Bradescu, O, Munteanu, M, Voitec, M, Vlaiculescu, M, Hancu, N, Diaconu Sotropa, M, Lupu, S, Mateescu, A, Carlan, L, Marton, R, Lupusoru, D, Mot, A, Coman, A, Zaharie, D, Rebrov, A, Shutemova, E, Bolieva, L, Khalimov, Y, Statsenko, M, Galyavich, A, Koziolova, N, Shapovalova, Y, Pavlysh, E, Strongin, L, Vertkin, A, Vishneva, E, Pavlova, M, Khasanov, N, Antsiferov, M, Gavrisheva, I, Sokolova, N, Vorobyev, S, Morugova, T, Sinitsina, I, Ezhov, A, Kobalava, Z, Belenkiy, D, Supryadkina, T, Kazakov, Y, Oschepkova, E, Dreval, A, Novikova, T, Vishnevsky, A, Chizhov, D, Akatova, E, Vorokhobina, N, Ivanov, I, Dudinskaya, E, Konstantinov, V, Kanderkova, D, Pavlik, L, Raslova, K, Paulovic, V, Babikova, J, Belesova, K, Merciakova, M, Truban, J, Vargova, A, Fabryova, L, Slovenska, M, Plasil, R, Tomasova, L, Kollarova, D, Spodniakova, D, Kosikova, M, Dzuponova, J, Kurcova, I, Skripova, D, Gabrisova, A, Kalinova, S, Ranjith, N, Burgess, L, Mitha, I, Conradie, M, Distiller, L, Pillai, P, Pillay, S, Horak, A, Nethononda, R, van den Berg, E, Nortje, H, Bayat, J, Corbett, C, Abelson, M, van Zyl, L, Pillay, T, Wing, J, Kapp, C, Hidalgo Urbano, R, Gonzalez Juanatey, J, Blanco Coronado, J, Bruguera Cortada, J, Ferreiro Gutierrez, J, Quesada Simon, M, Castro, A, Delgado Alvarez, E, Freixa, R, Boada, A, Larnefeldt, H, Mooe, T, Koskinen, P, Lagerback, P, Linderfalk, C, Liu, B, Berndtsson Blom, K, Tengmark, B, Lindholm, C, Oweling, M, Albertsson, P, Alvarsson, M, Fant, S, Berglund, O, Hsia, C, Fang, C, Ueng, K, Wang, K, Lai, W, Mamanasiri, S, Wongvipaporn, C, Kuanprasert, S, Thongsri, T, Srimahachota, S, Boonyavarakul, A, Suwanwalaikorn, S, Tantiwong, P, Sritara, P, Sriwijitkamol, A, Sanguanwong, S, Chotinaiwattarakul, C, Piyayotai, D, Balci, M, Orbay, E, Saygili, F, Oguz, A, Altuntas, Y, Comlekci, A, Karpenko, O, Tkach, S, Vlasenko, M, Fushtey, I, Pertseva, T, Reshotko, D, Mostovoy, Y, Vizir, V, Kraiz, I, Amosova, K, Batushkin, V, Tseluyko, V, Koval, O, Strang, C, Bodalia, B, Pieters, R, Turner, W, Asamoah-Owusu, N, White, C, Calvert, J, Mcnally, D, Jones, N, Mckaig, G, Thompson, J, Mohr, S, Simpson, H, Conn, P, Mccoye, A, Rivero, O, Yazdani, S, Ince, C, Zeitlin, J, Wharton, T, Platt, G, Anderson, R, Angueira-Serrano, E, Lillestol, M, Hanlon, B, Soufer, J, Garcia, B, Iteld, B, Venugopal, C, Ahmed, A, Duardo-Guerra, Y, Jetty, P, Miranda, A, Wahlen, J, Lederman, S, Cohen, K, Lake, L, French, W, Tahirkheli, N, Baker, S, Stoltz, R, Wilson, J, Nadar, V, Brown, J, Larrain, G, Wiseman, A, Ruoff, G, Williams, M, Tan, A, Hartman, I, Singh, N, Graf, R, Wakefield, P, Mcneill, R, Byars, W, Reyes Almodovar, R, Jones, S, Kantaros, L, Hegedosh, N, Graves, M, Bernstein, M, Falkowski, S, Bialow, M, Paraschos, A, Dagher, G, Arif, A, Condit, J, Chaykin, L, Grunstra, B, Earl, J, Unks, D, Srivastava, S, Benson, M, Huffman, C, Miller, G, Willis, J, Bender, K, Martin, E, Blackmore, R, Rohr, K, Chilka, S, Gadowski, G, Fitz-Patrick, D, Benjamin, S, Morin, D, Zias Dilena, A, Acosta, R, Claassen, D, Miranda, F, Raad, G, Inzerello, A, Porter, J, Bhattacharya, A, Gutmann, J, Korpas, D, Syed, M, Zieve, F, Raisinghani, A, Alam, S, Bartkowiak, A, Boccalandro, F, Talano, J, Mercado, A, Krichmar, P, Oldfield, C, Adams, K, Gorman, T, Lewis, D, Shah, R, Shockey, G, Lefebvre, G, Andrawis, N, Tami, L, Bittar, N, Khan, M, Rink, L, Hendrix, E, Wood, J, Robinson, J, Pavon, H, Irfan, M, Gonzalez, E, Singal, R, Shore, K, Saba, F, Bianco, J, Erickson, B, Gorson, D, Puri, S, Arauz-Pacheco, C, Forman, S, Akyea-Djamson, A, Lieber, I, Barker, B, Desai, P, Sotolongo, C, Steinhoff, J, Hill, R, Radin, M, Patel, R, Lieberman, S, Wenocur, H, Dagogo-Jack, S, Lupovitch, S, Ison, R, Bacharach, J, Diogo, J, Mazzella, M, Greenwald, J, Quadrel, M, Mayer, N, Datu, J, Mccartney, M, Bruce, T, Singal, D, Turner, J, Videau, B, Fritz, R, Fox, D, Calatayud, G, Sheldon, W, Kereiakes, D, Thomas, J, Salacata, A, Mccullum, K, Harris, B, de Souza, J, Rahman, A, Blumenthal, S, Narayan, P, Bloch, M, Augenbraun, C, Bernstein, R, Perlman, R, Berman, J, Labryer, L, Wynne, A, Fish, J, Zarich, S, Gabra, N, Popeil, L, Hermany, P, Barreto, A, Pomposini, D, Gonzalez-Campoy, J, Langer, M, Bayron, C, Suneja, R, Kamlet, J, Wheeler, K, Hurley, S, Sharma, S, Wefald, F, Hershon, K, O'Connor, T, Pueblitz, G, Laguerre, J, Amin, M, Alfonso, T, Jaffrani, N, Isserman, S, Portnay, E, Vlastaris, A, Dy, J, Hagan, M, Noveck, H, Kraft, P, Andersen, J, Foley, B, Carr, K, Gelormini, J, Williams, T, Landau, C, Richwine, R, Thakkar, M, Karim, A, Madhun, Z, Francyk, D, Lamantia, J, Baker, B, Zhang, W, Lev, V, Hasan, M, Captain, A, Herzog, W, Friedman, K, Lawson, W, Desai, V, Ow, C, Simons, R, Mandviwala, M, Le, T, Hack, T, Zebrack, J, Henderson, D, Dejulia, J, Mehta, R, Reza, S, Poonawala, R, Awad, A, Velasquez, M, Mohiuddin, S, Salazar Sharma, M, Myrick, G, Gottlieb, D, Ovalle, F, Alfieri, A, Ahmed, S, Bohula, E, Donahoe, S, Longshaw, K, Eshaghian, S, Lash, J, Goldberg, R, Fox, B, Mostel, E, Dobies, D, Ward, H, Burbano, J, Puleo, P, Lenhard, M, Korn, D, Thadani, U, Bradley, A, Kmetzo, J, Heasley, E, Raikhel, M, Mahr, N, Bittar, G, Fuentes, F, Raghu, P, Diep, T, Tran, Q, Tran, N, Nguyen, D, and Nguyen, V

Subjects
Male, medicine.medical_specialty, dapagliflozin, placebo, [SDV]Life Sciences [q-bio], Renal function, Type 2 diabetes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glucosides, Diabetes mellitus, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Benzhydryl Compounds, Dapagliflozin, Sodium-Glucose Transporter 2 Inhibitors, ComputingMilieux_MISCELLANEOUS, Aged, Heart Failure, Canagliflozin, business.industry, [SDV.BA]Life Sciences [q-bio]/Animal biology, General Medicine, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Hospitalization, Diabetes Mellitus, Type 2, chemistry, Cardiovascular Diseases, Heart failure, Cardiology, Female, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Mace, medicine.drug
Abstract

BACKGROUND The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. METHODS We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to ≥60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. RESULTS We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, who were followed for a median of 4.2 years. In the primary safety outcome analysis, dapagliflozin met the prespecified criterion for noninferiority to placebo with respect to MACE (upper boundary of the 95% confidence interval [CI], ≥1.3; P≥0.001 for noninferiority). In the two primary efficacy analyses, dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group and 9.4% in the placebo group; hazard ratio, 0.93; 95% CI, 0.84 to 1.03; P = 0.17) but did result in a lower rate of cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; hazard ratio, 0.83; 95% CI, 0.73 to 0.95; P = 0.005), which reflected a lower rate of hospitalization for heart failure (hazard ratio, 0.73; 95% CI, 0.61 to 0.88); there was no between-group difference in cardiovascular death (hazard ratio, 0.98; 95% CI, 0.82 to 1.17). A renal event occurred in 4.3% in the dapagliflozin group and in 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67 to 0.87), and death from any cause occurred in 6.2% and 6.6%, respectively (hazard ratio, 0.93; 95% CI, 0.82 to 1.04). Diabetic ketoacidosis was more common with dapagliflozin than with placebo (0.3%vs. 0.1%, P = 0.02), as was the rate of genital infections that led to discontinuation of the regimen or that were considered to be serious adverse events (0.9% vs. 0.1%, P≥0.001). CONCLUSIONS In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease, treatment with dapagliflozin did not result in a higher or lower rate of MACE than placebo but did result in a lower rate of cardiovascular death or hospitalization for heart failure, a finding that reflects a lower rate of hospitalization for heart failure. (Funded by AstraZeneca; DECLARETIMI 58 ClinicalTrials.gov number, NCT01730534

Published
2019
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44. Contributors

Author

Akers, Thomas K., primary, Baumgarten, Clive M., additional, Behbehani, M.M., additional, Blumenthal, Kenneth, additional, Bridge, John H.B., additional, Bryant, S.H., additional, Cuppoletti, John, additional, Darszon, A., additional, DeFelice, Louis J., additional, Dedman, John R., additional, Edes, Istvan, additional, Feher, Joseph J., additional, Ferguson, Donald G., additional, Fleischman, Darrell, additional, Freedman, Jeffrey C., additional, Gallo-Payet, Nicole, additional, Woodland Hastings, J., additional, Michael Hendrix, E., additional, Hermsmeyer, R. Kent, additional, Kaetzel, Marcia A., additional, Kaneshiro, Edna S., additional, Kranias, Evangelia G., additional, Larsen, William J., additional, Lecar, Harold, additional, Rock Levinson, Simon, additional, Lieberman, Michael A., additional, Liévano, A., additional, Mazzanti, Michele, additional, Meissner, Gerhard, additional, Misler, Stanley, additional, Morris, Catherine E., additional, Nilius, Bernd, additional, Paul, R.J., additional, Daniel Payet, Marcel, additional, Pincus, Matthew R., additional, Pun, Raymund Y.K., additional, Putnam, Robert W., additional, Roper, S., additional, Schroeder, Friedhelm, additional, Sleight, Richard G., additional, Sperelakis, Nicholas, additional, Stout, Richard G., additional, Suszkiw, Janusz B., additional, Wahler, Gordon M., additional, Taylor Wallick, Earl, additional, Westbrook, Gary L., additional, Gibson Wood, W., additional, Yatani, Atsuko, additional, and Zimmerman, Anita L., additional

Published
1995
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50. Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial

Author

Bohula, Erin A, primary, Scirica, Benjamin M, additional, Inzucchi, Silvio E, additional, McGuire, Darren K, additional, Keech, Anthony C, additional, Smith, Steven R, additional, Kanevsky, Estella, additional, Murphy, Sabina A, additional, Leiter, Lawrence A, additional, Dwyer, Jamie P, additional, Corbalan, Ramon, additional, Hamm, Christian, additional, Kaplan, Lee, additional, Nicolau, Jose Carlos, additional, Ophuis, Ton Oude, additional, Ray, Kausik K, additional, Ruda, Mikhail, additional, Spinar, Jindrich, additional, Patel, Tushar, additional, Miao, Wenfeng, additional, Perdomo, Carlos, additional, Francis, Bruce, additional, Dhadda, Shobha, additional, Bonaca, Marc P, additional, Ruff, Christian T, additional, Sabatine, Marc S, additional, Wiviott, Stephen D, additional, Inzucchi, Silvio, additional, Keech, Anthony, additional, Satlin, Andrew, additional, Brown, Conville, additional, Budaj, Andrzej, additional, Dwyer, Jamie, additional, Garcia-Castillo, Armando, additional, Gupta, Milan, additional, Oude Ophuis, Ton, additional, Ray, Kauski, additional, Weissman, Neil, additional, White, Harvey D, additional, Amerena, J, additional, Arstall, M, additional, Colquhoun, D, additional, Jayasinghe, R, additional, Lee, A, additional, Lehman, R, additional, Moses, R, additional, Proietto, J, additional, Purnell, P, additional, Waites, J, additional, Blombery, P, additional, Cross, D, additional, Worthley, M, additional, d'Emden, M, additional, Selvanayagam, J, additional, Oqueli, RE, additional, Whelan, A, additional, Garrahy, P, additional, de Looze, F, additional, Ninio, D, additional, Horowitz, J, additional, William, M, additional, Suranyi, M, additional, Wittert, G, additional, Le May, M, additional, Pandey, AS, additional, Vizel, S, additional, Labonte, R, additional, Beaudry, Y, additional, Fortin, C, additional, Bell, A, additional, Kouz, S, additional, St-Amour, É, additional, Bata, I, additional, St Maurice, F, additional, Chehayeb, R, additional, Constance, C, additional, Wong, G, additional, Hess, A, additional, Liutkus, J, additional, Poirier, P, additional, Teitelbaum, I, additional, Berlingieri, J, additional, Cha, J, additional, Hartleib, M, additional, Heffernan, M, additional, Twum-Barima, D, additional, Pandith, V, additional, Aronson, R, additional, Goldenberg, R, additional, Ajala, B, additional, Jain, A, additional, Ross, S, additional, Bajaj, H, additional, Khandwala, H, additional, Yared, Z, additional, Gupta, N, additional, Bédard, J, additional, Wharton, S, additional, Blouin, F, additional, Savard, D, additional, Shukla, D, additional, Cobos, J, additional, Godoy, G, additional, Perez, L, additional, Pincetti, C, additional, Saavedra Guajardo, V, additional, Varleta, P, additional, Conejeros, C, additional, Lanas, F, additional, Bayram Llamas, E, additional, Cardona Muñoz, E, additional, Garcia, R, additional, Garza Ruiz, J, additional, Llamas Esperon, G, additional, Lopez Rosas, E, additional, Melendez Mier, G, additional, Ramos, G, additional, Hart, H, additional, Scott, D, additional, Ternouth, I, additional, Benatar, J, additional, Elliott, J, additional, Cutfield, R, additional, Manning, P, additional, Williams, M, additional, Ferrier, K, additional, Scott, R, additional, Wilson, S, additional, Leikis, R, additional, Nirmalaraj, BK, additional, Krzyżagórska, E, additional, Miękus, P, additional, Bronisz, M, additional, Mirek-Bryniarska, E, additional, Łanda, K, additional, Stasiewski, A, additional, Żechowicz, T, additional, Zytkiewicz-Jaruga, D, additional, Korecki, J, additional, Ogórek, M, additional, Pawłowicz, L, additional, Piepiorka, M, additional, Skierkowska, J, additional, Stankiewicz, A, additional, Szyprowska, E, additional, Witek, R, additional, Bochenek, A, additional, Kończakowski, P, additional, Wojnowski, Ł, additional, Wujkowski, M, additional, Cymerman, K, additional, Korzeniak, R, additional, Mąder, P, additional, Mikłaszewicz, B, additional, Stachlewski, P, additional, Goch, A, additional, Pomiećko, W, additional, Skórski, M, additional, Romanowski, L, additional, Jusiak, K, additional, Laskowska-Derlaga, E, additional, Bijata-Bronisz, R, additional, Kaźmierczak, J, additional, Goldberg, R, additional, Henderson, D, additional, Korban, E, additional, Rohr, K, additional, Claxton, E, additional, Weiss, R, additional, Angiolillo, D, additional, Boccalandro, F, additional, Chu, K, additional, Thorn, E, additional, Randhawa, P, additional, Singh, N, additional, Bittar, G, additional, Guarnieri, T, additional, Saeed, S, additional, Sharma, S, additional, Shepard, M, additional, French, W, additional, Desai, P, additional, Bernstein, R, additional, Rogers, W, additional, Singal, R, additional, Schneider, R, additional, Shanes, J, additional, Ong, S, additional, Condit, J, additional, Donahoe, S, additional, Brill, D, additional, Einhorn, D, additional, Ebrahimi, R, additional, Labroo, A, additional, Graf, R, additional, Scott, J, additional, Hoekstra, J, additional, Jetty, P, additional, Luckasen, G, additional, O'Donnell, P, additional, Gonte, W, additional, Pomposini, D, additional, Quadrel, M, additional, Koren, M, additional, Schlager, D, additional, Schramm, E, additional, Singal, D, additional, Lupovitch, S, additional, Soni, A, additional, Seigel, P, additional, Roberts, J, additional, Soufer, J, additional, Reza, S, additional, Quinlan, E, additional, Moretto, T, additional, First, B, additional, Khan, M, additional, Chilka, S, additional, Colfer, H, additional, Teklinski, A, additional, Wallace-Wilding, K, additional, Ellison, H, additional, Muse, D, additional, Aronoff, S, additional, Higgins, A, additional, Patel, S, additional, Elinoff, V, additional, Karim, A, additional, Awasty, V, additional, Chuang, R, additional, Roseman, H, additional, Dugano-Daphnis, P, additional, Albert, M, additional, Sheikh, K, additional, Bays, H, additional, Kaster, S, additional, Goldstein, M, additional, Rubino, D, additional, Calatayud, G, additional, Snyder, H, additional, Williams, T, additional, Hershon, K, additional, Hagan, M, additional, Isserman, S, additional, Kahn, B, additional, Anderson, J, additional, Gimness, MP, additional, Raisinghani, A, additional, Christina, M, additional, Raikhel, M, additional, Gillespie, E, additional, Portnay, E, additional, Heiman, M, additional, Qureshi, M, additional, Lee, J, additional, Blonder, R, additional, Cucher, F, additional, Miller, G, additional, Kotlaba, D, additional, Cornett, G, additional, Beavins, J, additional, Augenbraun, C, additional, Reinhardt, S, additional, Bartkowiak, A, additional, Salacata, A, additional, Blevins, T, additional, Benjamin, S, additional, Diener, J, additional, George, W, additional, Barker, B, additional, Richwine, R, additional, Baldari, D, additional, Alfieri, A, additional, Barreto, A, additional, Zhang, L, additional, Shah, R, additional, Hendrix, E, additional, Subramaniyam, V, additional, Hurley, S, additional, Lillestol, M, additional, O'Donoghue, M, additional, Shayani, S, additional, Ryan, E, additional, Call, R, additional, Zemel, L, additional, Chang, A, additional, Kivitz, A, additional, Freyne, B, additional, Bland, V, additional, Shore, K, additional, Mostel, E, additional, Uzoaga, E, additional, Andrawis, N, additional, Gabra, N, additional, Ghitis, A, additional, Sabatino, K, additional, Browder, D, additional, Varma, S, additional, Smith, S, additional, Fink, R, additional, Aycock, GR, additional, Doty, WD, additional, Alfonso, T, additional, Eshaghian, S, additional, Karlsberg, R, additional, Zarich, S, additional, Landau, C, additional, McKenzie, M, additional, Krause, R, additional, Davis, W, additional, Haddad, T, additional, Voyce, S, additional, Alford, C, additional, LeDoux, J, additional, O'Dea, D, additional, Park, J, additional, Aroda, V, additional, Getaneh, A, additional, Graham, B, additional, Bhagwat, R, additional, Korn, D, additional, Ruoff, G, additional, Wiseman, A, additional, Lieber, I, additional, Fialkow, J, additional, Gonzalez-Campoy, JM, additional, Bayron, C, additional, Bertolet, B, additional, Lash, J, additional, Gerrish, C, additional, Robertson, D, additional, Rosenfeld, J, additional, Seidner, M, additional, Agaiby, J, additional, Silverfield, J, additional, Sugimoto, D, additional, Lubin, B, additional, Alhaddad, M, additional, Lui, H, additional, Lakin, G, additional, Chokshi, S, additional, Donovan, D, additional, Felten, W, additional, Minton, S, additional, Kimmelstiel, C, additional, Kuvin, J, additional, Still, C, additional, Byars, W, additional, Talano, J, additional, Desai, V, additional, Bradley, AJ, additional, Baker, S, additional, Chane, M, additional, Mercado, A, additional, Baron, S, additional, Harris, B, additional, Mayer, N, additional, Concha, M, additional, Carr, K, additional, Chaykin, L, additional, Willis, J, additional, Clay, A, additional, Fenstad, E, additional, Furda, J, additional, Peterson, P, additional, Chang, M, additional, Aronne, L, additional, Jones, D, additional, Prashad, R, additional, Benson, M, additional, Stegemoller, R, additional, Longshaw, K, additional, Saleh, J, additional, Jennings, W, additional, Detweiler, R, additional, Viswanath, D, additional, Patel, R, additional, Lederman, S, additional, Weinstein, D, additional, Korabathina, R, additional, Singh, V, additional, Rosen, J, additional, Estevez, R, additional, Levin, P, additional, McNeill, R, additional, Kalen, V, additional, Reed, J, additional, Ashley, R, additional, Herman, L, additional, Tsai, Y, additional, Kayne, D, additional, White, A, additional, Hussain, I, additional, Tami, L, additional, Cohen, K, additional, Robinson, J, additional, Fuchs-Ertman, D, additional, Platt, G, additional, Belardo, L, additional, Reddy, R, additional, Rosendorff, C, additional, Saba, F, additional, Powell, S, additional, Anderson, K, additional, Abidi, M, additional, Rezkalla, S, additional, Paraschos, A, additional, Wilson, J, additional, Moursi, M, additional, Shah, A, additional, Nadar, V, additional, Stonesifer, L, additional, Bialow, M, additional, Cannon, K, additional, Ellison, W, additional, Stedman, M, additional, Brown, J, additional, Harper, W, additional, Lucas, KJ, additional, DiGiovanna, M, additional, Rodbard, H, additional, Biscoveanu, M, additional, Davis, C, additional, Hall, J, additional, Littlefield, R, additional, Gorman, T, additional, Kereiakes, D, additional, Chang, FM, additional, Tatu, H, additional, Cheung, D, additional, Kaine, J, additional, Knutson, T, additional, Logemann, T, additional, Pueblitz, G, additional, Bianco, J, additional, Henson, B, additional, Neustel, M, additional, Gelernt, M, additional, Nelson, W, additional, Moriarty, K, additional, Lefebvre, G, additional, Maw, K, additional, Rink, L, additional, Behn, P, additional, Studdard, H, additional, Argoud, G, additional, O'Connor, T, additional, Krichmar, P, additional, Raad, G, additional, Pereles-Ortiz, J, additional, Sorli, C, additional, Cohen, A, additional, Pettis, K, additional, Cavanaugh, B, additional, Phillips, C, additional, Wahlen, J, additional, Radin, D, additional, Rider, J, additional, Kosinski, E, additional, Leimbach, W, additional, Odhav, A, additional, Hakas, J, additional, Tan, A, additional, Howell, M, additional, Wombolt, D, additional, Fishman, N, additional, Shah, P, additional, Wylie, P, additional, Arauz-Pacheco, C, additional, Cavale, A, additional, George, A, additional, Kroll, R, additional, Krantzler, J, additional, Tahirkheli, N, additional, Jabro, M, additional, Newell, M, additional, Mullen, P, additional, Gencheff, N, additional, Meli, J, additional, Vora, K, additional, Kotek, L, additional, Pyzdrowski, K, additional, Paez, H, additional, Moran, J, additional, Tannenbaum, A, additional, Deck, K, additional, Busch, R, additional, Levinson, L, additional, Azizad, M, additional, Whitaker, J, additional, Fox, B, additional, Huffman, C, additional, Ashraf, M, additional, Diogo, J, additional, Kushner, R, additional, Tallet, J, additional, Channamsetty, V, additional, Suh, D, additional, Atieh, M, additional, Navas, J, additional, Young, V, additional, Shaw, S, additional, Dor, I, additional, Duffy, B, additional, Rubin, P, additional, Lewis, D, additional, Kaye, W, additional, Benton, R, additional, Burbano, J, additional, Hotchkiss, D, additional, Magno, A, additional, Alberton, A, additional, Collins, J, additional, Alvarado, O, additional, Stich, M, additional, Mahal, S, additional, Liu, J, additional, Hong, M, additional, Dy, J, additional, Block, B, additional, Lamantia, J, additional, Pritchard, J, additional, Davis, M, additional, Srivastava, S, additional, Bilazarian, S, additional, Rosario, R, additional, McCartney, M, additional, Blumberg, V, additional, Rajan, R, additional, Martin, E, additional, Wright, S, additional, Brinson, C, additional, Johnston, J, additional, Graves, M, additional, Dominguez, M, additional, McKenzie, W, additional, Abadier, R, additional, Tran, C, additional, Castello, R, additional, Morawski, E, additional, White, J, additional, Morris, F, additional, Perez, A, additional, Trueba, P, additional, Sanchez, M, additional, Andersen, J, additional, Kastelic, R, additional, Khan, J, additional, Rodriguez, H, additional, Izquierdo, W, additional, Matias, A, additional, Essandoh, L, additional, and Ince, C, additional

Published
2018
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