1. Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): a post-hoc analysis of a randomised, double-blind trial
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Subodh Verma, Nitish K Dhingra, Javed Butler, Stefan D Anker, Joao Pedro Ferreira, Gerasimos Filippatos, James L Januzzi, Carolyn S P Lam, Naveed Sattar, Barbara Peil, Matias Nordaby, Martina Brueckmann, Stuart J Pocock, Faiez Zannad, Milton Packer, M Packer, S Anker, J Butler, G Filippatos, S Pocock, F Zannad, JP Ferreira, M Brueckmann, J George, W Jamal, FK Welty, M Palmer, T Clayton, KG Parhofer, TR Pedersen, B Greenberg, MA Konstam, KR Lees, P Carson, W Doehner, A Miller, M Haas, S Pehrson, M Komajda, I Anand, J Teerlink, A Rabinstein, T Steiner, H Kamel, G Tsivgoulis, J Lewis, J Freston, N Kaplowitz, J Mann, J Petrie, S Perrone, S Nicholls, S Janssens, E Bocchi, N Giannetti, S Verma, J Zhang, J Spinar, M-F Seronde, M Boehm, B Merkely, V Chopra, M Senni, S Taddi, H Tsutsui, D-J Choi, E Chuquiure, HPB La Rocca, P Ponikowski, JRG Juanatey, I Squire, J Januzzi, I Pina, R Bernstein, A Cheung, J Green, S Kaul, C Lam, G Lip, N Marx, P McCullough, C Mehta, J Rosenstock, N Sattar, B Scirica, S Shah, C Wanner, D Aizenberg, L Cartasegna, F Colombo Berra, H Colombo, M Fernandez Moutin, J Glenny, C Alvarez Lorio, D Anauch, R Campos, A Facta, A Fernandez, R Ahuad Guerrero, L Lobo Márquez, RA Leon de la Fuente, M Mansilla, M Hominal, E Hasbani, M Najenson, G Moises Azize, H Luquez, L Guzman, H Sessa, M Amuchástegui, O Salomone, E Perna, D Piskorz, M Sicer, D Perez de Arenaza, C Zaidman, S Nani, C Poy, J Resk, R Villarreal, C Majul, T Smith Casabella, S Sassone, A Liberman, G Carnero, A Caccavo, M Berli, N Budassi, J Bono, A Alvarisqueta, J Amerena, K Kostner, A Hamilton, A Begg, J Beltrame, D Colquhoun, G Gordon, A Sverdlov, G Vaddadi, J Wong, J Coller, D Prior, A Friart, A Leone, G Vervoort, P Timmermans, P Troisfontaines, C Franssen, T Sarens, H Vandekerckhove, P Van De Borne, F Chenot, J De Sutter, E De Vuyst, P Debonnaire, M Dupont, O Pereira Dutra, LH Canani, MdC Vieira Moreira, W de Souza, LM Backes, L Maia, B De Souza Paolino, ER Manenti, W Saporito, F Villaça Guimarães Filho, T Franco Hirakawa, LA Saliba, FC Neuenschwander, CA de Freitas Zerbini, G Gonçalves, Y Gonçalves Mello, J Ascenção de Souza, L Beck da Silva Neto, EA Bocchi, J Da Silveira, JB de Moura Xavier Moraes Junior, JD de Souza Neto, M Hernandes, HC Finimundi, CR Sampaio, E Vasconcellos, FJ Neves Mancuso, MM Noya Rabelo, M Rodrigues Bacci, F Santos, M Vidotti, MV Simões, FL Gomes, C Vieira Nascimento, D Precoma, FA Helfenstein Fonseca, JA Ribas Fortes, PE Leães, D Campos de Albuquerque, JF Kerr Saraiva, S Rassi, FA Alves da Costa, G Reis, S Zieroth, D Dion, D Savard, R Bourgeois, C Constance, K Anderson, M-H Leblanc, D Yung, E Swiggum, L Pliamm, Y Pesant, B Tyrrell, T Huynh, J Spiegelman, J-P Lavoie, M Hartleib, R Bhargava, L Straatman, S Virani, A Costa-Vitali, L Hill, M Heffernan, Y Khaykin, J Ricci, M Senaratne, A Zhai, B Lubelsky, M Toma, L Yao, R McKelvie, L Noronha, M Babapulle, A Pandey, G Curnew, A Lavoie, J Berlingieri, S Kouz, E Lonn, R Chehayeb, Y Zheng, Y Sun, H Cui, Z Fan, X Han, X Jiang, Q Tang, J Zhou, Z Zheng, X Zhang, N Zhang, Y Zhang, A Shen, J Yu, J Ye, Y Yao, J Yan, X Xu, Z Wang, J Ma, Y Li, S Li, S Lu, X Kong, Y Song, G Yang, Z Yao, Y Pan, X Guo, Z Sun, Y Dong, J Zhu, D Peng, Z Yuan, J Lin, Y Yin, O Jerabek, H Burianova, T Fiala, J Hubac, O Ludka, Z Monhart, P Vodnansky, K Zeman, D Foldyna, J Krupicka, I Podpera, L Busak, M Radvan, Z Vomacka, R Prosecky, R Cifkova, V Durdil, J Vesely, J Vaclavik, P Cervinka, A Linhart, T Brabec, R Miklik, H Bourhaial, H-G Olbrich, S Genth-Zotz, E Kemala, B Lemke, M Böhm, S Schellong, W Rieker, T Heitzer, H Ince, M Faghih, A Birkenfeld, A Begemann, A Ghanem, A Ujeyl, S von Haehling, T Dorsel, J Bauersachs, M Prull, F Weidemann, H Darius, G Nickenig, A Wilke, J Sauter, U Rauch-Kroehnert, N Frey, CP Schulze, W König, L Maier, F Menzel, N Proskynitopoulos, H-H Ebert, H-E Sarnighausen, H-D Düngen, M Licka, C Stellbrink, B Winkelmann, N Menck, JL López-Sendón, L de la Fuente Galán, JF Delgado Jiménez, N Manito Lorite, M Pérez de Juan Romero, E Galve Basilio, F Cereto Castro, JR González Juanatey, JJ Gómez, M Sanmartín Fernández, X Garcia-Moll Marimon, D Pascual Figal, R Bover Freire, E Bonnefoy Cudraz, A Jobbe Duval, D Tomasevic, G Habib, R Isnard, F Picard, P Khanoyan, J-L Dubois-Rande, M Galinier, F Roubille, J Alexandre, D Babuty, N Delarche, J-B Berneau, N Girerd, M Saxena, G Rosano, Z Yousef, C Clifford, C Arden, A Bakhai, C Boos, G Jenkins, C Travill, D Price, L Koenyves, F Lakatos, A Matoltsy, E Noori, Z Zilahi, P Andrassy, S Kancz, G Simon, T Sydo, A Vorobcsuk, RG Kiss, K Toth, I Szakal, L Nagy, T Barany, A Nagy, E Szolnoki, VK Chopra, S Mandal, V Rastogi, B Shah, A Mullasari, J Shankar, V Mehta, A Oomman, U Kaul, S Komarlu, D Kahali, A Bhagwat, V Vijan, NK Ghaisas, A Mehta, J Kashyap, Y Kothari, S TaddeI, M Scherillo, V Zacà, S Genovese, A Salvioni, A Fucili, F Fedele, F Cosmi, M Volpe, C Mazzone, G Esposito, M Doi, H Yamamoto, S Sakagami, S Oishi, Y Yasaka, H Tsuboi, Y Fujino, S Matsuoka, Y Watanabe, T Himi, T Ide, M Ichikawa, Y Kijima, T Koga, S Yuda, K Fukui, T Kubota, M Manita, H Fujinaga, T Matsumura, Y Fukumoto, R Kato, Y Kawai, G Hiasa, Y Kazatani, M Mori, A Ogimoto, M Inoko, M Oguri, M Kinoshita, K Okuhara, N Watanabe, Y Ono, K Otomo, Y Sato, T Matsunaga, A Takaishi, N Miyagi, H Uehara, H Takaishi, H Urata, T Kataoka, H Matsubara, T Matsumoto, T Suzuki, N Takahashi, M Imamaki, T Yoshitama, T Saito, H Sekino, Y Furutani, M Koda, T Shinozaki, K Hirabayashi, R Tsunoda, K Yonezawa, H Hori, M Yagi, M Arikawa, T Hashizume, R Ishiki, T Koizumi, K Nakayama, S Taguchi, M Nanasato, Y Yoshida, S Tsujiyama, T Nakamura, K Oku, M Shimizu, M Suwa, Y Momiyama, H Sugiyama, K Kobayashi, S Inoue, T Kadokami, K Maeno, K Kawamitsu, Y Maruyama, A Nakata, T Shibata, A Wada, H-J Cho, JO Na, B-S Yoo, J-O Choi, SK Hong, J-H Shin, M-C Cho, SH Han, J-O Jeong, J-J Kim, SM Kang, D-S Kim, MH Kim, G Llamas Esperon, J Illescas Díaz, P Fajardo Campos, J Almeida Alvarado, A Bazzoni Ruiz, J Echeverri Rico, I Lopez Alcocer, L Valle Molina, C Hernandez Herrera, C Calvo Vargas, FG Padilla Padilla, I Rodriguez Briones, EJJR Chuquiure Valenzuela, ME Aguilera Real, J Carrillo Calvillo, M Alpizar Salazar, JL Cervantes Escárcega, R Velasco Sanchez, N Al - Windy, L van Heerebeek, L Bellersen, H-P Brunner-La Rocca, J Post, GCM Linssen, M van de Wetering, R Peters, R van Stralen, R Groutars, P Smits, A Yilmaz, WEM Kok, P Van der Meer, P Dijkmans, R Troquay, AP van Alem, R Van de Wal, L Handoko, ICD Westendorp, PFMM van Bergen, BJWM Rensing, P Hoogslag, B Kietselaer, JA Kragten, FR den Hartog, A Alings, L Danilowicz-Szymanowicz, G Raczak, W Piesiewicz, W Zmuda, W Kus, P Podolec, W Musial, G Drelich, G Kania, P Miekus, S Mazur, A Janik, J Spyra, J Peruga, P Balsam, B Krakowiak, J Szachniewicz, M Ginel, J Grzybowski, W Chrustowski, P Wojewoda, A Kalinka, A Zurakowski, R Koc, M Debinski, W Fil, M Kujawiak, J Forys, M Kasprzak, M Krol, P Michalski, E Mirek-Bryniarska, K Radwan, G Skonieczny, K Stania, G Skoczylas, A Madej, J Jurowiecki, B Firek, B Wozakowska-Kaplon, K Cymerman, J Neutel, K Adams, P Balfour, A Deswal, A Djamson, P Duncan, M Hong, C Murray, D Rinde-Hoffman, S Woodhouse, R MacNevin, B Rama, C Broome-Webster, S Kindsvater, D Abramov, M Barettella, S Pinney, J Herre, A Cohen, K Vora, K Challappa, S West, S Baum, J Cox, S Jani, A Karim, A Akhtar, O Quintana, L Paukman, R Goldberg, Z Bhatti, M Budoff, E Bush, A Potler, R Delgado, B Ellis, J Dy, J Fialkow, R Sangrigoli, K Ferdinand, C East, S Falkowski, S Donahoe, R Ebrahimi, G Kline, B Harris, R Khouzam, N Jaffrani, N Jarmukli, N Kazemi, M Koren, K Friedman, W Herzog, J Silva Enciso, D Cheung, M Grover-McKay, P Hauptman, D Mikhalkova, V Hegde, J Hodsden, S Khouri, F McGrew, R Littlefield, P Bradley, B McLaurin, S Lupovitch, I Labin, V Rao, M Leithe, M Lesko, N Lewis, D Lombardo, S Mahal, V Malhotra, I Dauber, A Banerjee, J Needell, G Miller, L Paladino, K Munuswamy, M Nanna, E McMillan, M Mumma, M Napoli, W Nelson, T O'Brien, A Adlakha, A Onwuanyi, H Serota, J Schmedtje, A Paraschos, R Potu, C Sai-Sudhakar, M Saltzberg, A Sauer, P Shah, H Skopicki, H Bui, K Carr, G Stevens, N Tahirkheli, J Tallaj, K Yousuf, B Trichon, J Welker, P Tolerico, A Vest, R Vivo, X Wang, R Abadier, S Dunlap, N Weintraub, A Malik, P Kotha, V Zaha, G Kim, N Uriel, T Greene, A Salacata, R Arora, R Gazmuri, J Kobayashi, B Iteld, R Vijayakrishnan, R Dab, Z Mirza, V Marques, M Nallasivan, D Bensimhon, B Peart, H Saint-Jacques, K Barringhaus, J Contreras, A Gupta, S Koneru, V Nguyen, Verma, S, Dhingra, N, Butler, J, Anker, S, Ferreira, J, Filippatos, G, Januzzi, J, Lam, C, Sattar, N, Peil, B, Nordaby, M, Brueckmann, M, Pocock, S, Zannad, F, Packer, M, George, J, Jamal, W, Welty, F, Palmer, M, Clayton, T, Parhofer, K, Pedersen, T, Greenberg, B, Konstam, M, Lees, K, Carson, P, Doehner, W, Miller, A, Haas, M, Pehrson, S, Komajda, M, Anand, I, Teerlink, J, Rabinstein, A, Steiner, T, Kamel, H, Tsivgoulis, G, Lewis, J, Freston, J, Kaplowitz, N, Mann, J, Petrie, J, Perrone, S, Nicholls, S, Janssens, S, Bocchi, E, Giannetti, N, Zhang, J, Spinar, J, Seronde, M, Boehm, M, Merkely, B, Chopra, V, Senni, M, Taddi, S, Tsutsui, H, Choi, D, Chuquiure, E, La Rocca, H, Ponikowski, P, Juanatey, J, Squire, I, Pina, I, Bernstein, R, Cheung, A, Green, J, Kaul, S, Lip, G, Marx, N, Mccullough, P, Mehta, C, Rosenstock, J, Scirica, B, Shah, S, Wanner, C, Aizenberg, D, Cartasegna, L, Colombo Berra, F, Colombo, H, Fernandez Moutin, M, Glenny, J, Alvarez Lorio, C, Anauch, D, Campos, R, Facta, A, Fernandez, A, Ahuad Guerrero, R, Lobo Marquez, L, Leon de la Fuente, R, Mansilla, M, Hominal, M, Hasbani, E, Najenson, M, Moises Azize, G, Luquez, H, Guzman, L, Sessa, H, Amuchastegui, M, Salomone, O, Perna, E, Piskorz, D, Sicer, M, Perez de Arenaza, D, Zaidman, C, Nani, S, Poy, C, Resk, J, Villarreal, R, Majul, C, Smith Casabella, T, Sassone, S, Liberman, A, Carnero, G, Caccavo, A, Berli, M, Budassi, N, Bono, J, Alvarisqueta, A, Amerena, J, Kostner, K, Hamilton, A, Begg, A, Beltrame, J, Colquhoun, D, Gordon, G, Sverdlov, A, Vaddadi, G, Wong, J, Coller, J, Prior, D, Friart, A, Leone, A, Vervoort, G, Timmermans, P, Troisfontaines, P, Franssen, C, Sarens, T, Vandekerckhove, H, Van De Borne, P, Chenot, F, De Sutter, J, De Vuyst, E, Debonnaire, P, Dupont, M, Pereira Dutra, O, Canani, L, Vieira Moreira, M, de Souza, W, Backes, L, Maia, L, De Souza Paolino, B, Manenti, E, Saporito, W, Villaca Guimaraes Filho, F, Franco Hirakawa, T, Saliba, L, Neuenschwander, F, de Freitas Zerbini, C, Goncalves, G, Goncalves Mello, Y, Ascencao de Souza, J, Beck da Silva Neto, L, Da Silveira, J, de Moura Xavier Moraes Junior, J, de Souza Neto, J, Hernandes, M, Finimundi, H, Sampaio, C, Vasconcellos, E, Neves Mancuso, F, Noya Rabelo, M, Rodrigues Bacci, M, Santos, F, Vidotti, M, Simoes, M, Gomes, F, Vieira Nascimento, C, Precoma, D, Helfenstein Fonseca, F, Ribas Fortes, J, Leaes, P, Campos de Albuquerque, D, Kerr Saraiva, J, Rassi, S, Alves da Costa, F, Reis, G, Zieroth, S, Dion, D, Savard, D, Bourgeois, R, Constance, C, Anderson, K, Leblanc, M, Yung, D, Swiggum, E, Pliamm, L, Pesant, Y, Tyrrell, B, Huynh, T, Spiegelman, J, Lavoie, J, Hartleib, M, Bhargava, R, Straatman, L, Virani, S, Costa-Vitali, A, Hill, L, Heffernan, M, Khaykin, Y, Ricci, J, Senaratne, M, Zhai, A, Lubelsky, B, Toma, M, Yao, L, Mckelvie, R, Noronha, L, Babapulle, M, Pandey, A, Curnew, G, Lavoie, A, Berlingieri, J, Kouz, S, Lonn, E, Chehayeb, R, Zheng, Y, Sun, Y, Cui, H, Fan, Z, Han, X, Jiang, X, Tang, Q, Zhou, J, Zheng, Z, Zhang, X, Zhang, N, Zhang, Y, Shen, A, Yu, J, Ye, J, Yao, Y, Yan, J, Xu, X, Wang, Z, Ma, J, Li, Y, Li, S, Lu, S, Kong, X, Song, Y, Yang, G, Yao, Z, Pan, Y, Guo, X, Sun, Z, Dong, Y, Zhu, J, Peng, D, Yuan, Z, Lin, J, Yin, Y, Jerabek, O, Burianova, H, Fiala, T, Hubac, J, Ludka, O, Monhart, Z, Vodnansky, P, Zeman, K, Foldyna, D, Krupicka, J, Podpera, I, Busak, L, Radvan, M, Vomacka, Z, Prosecky, R, Cifkova, R, Durdil, V, Vesely, J, Vaclavik, J, Cervinka, P, Linhart, A, Brabec, T, Miklik, R, Bourhaial, H, Olbrich, H, Genth-Zotz, S, Kemala, E, Lemke, B, Bohm, M, Schellong, S, Rieker, W, Heitzer, T, Ince, H, Faghih, M, Birkenfeld, A, Begemann, A, Ghanem, A, Ujeyl, A, von Haehling, S, Dorsel, T, Bauersachs, J, Prull, M, Weidemann, F, Darius, H, Nickenig, G, Wilke, A, Sauter, J, Rauch-Kroehnert, U, Frey, N, Schulze, C, Konig, W, Maier, L, Menzel, F, Proskynitopoulos, N, Ebert, H, Sarnighausen, H, Dungen, H, Licka, M, Stellbrink, C, Winkelmann, B, Menck, N, Lopez-Sendon, J, de la Fuente Galan, L, Delgado Jimenez, J, Manito Lorite, N, Perez de Juan Romero, M, Galve Basilio, E, Cereto Castro, F, Gonzalez Juanatey, J, Gomez, J, Sanmartin Fernandez, M, Garcia-Moll Marimon, X, Pascual Figal, D, Bover Freire, R, Bonnefoy Cudraz, E, Jobbe Duval, A, Tomasevic, D, Habib, G, Isnard, R, Picard, F, Khanoyan, P, Dubois-Rande, J, Galinier, M, Roubille, F, Alexandre, J, Babuty, D, Delarche, N, Berneau, J, Girerd, N, Saxena, M, Rosano, G, Yousef, Z, Clifford, C, Arden, C, Bakhai, A, Boos, C, Jenkins, G, Travill, C, Price, D, Koenyves, L, Lakatos, F, Matoltsy, A, Noori, E, Zilahi, Z, Andrassy, P, Kancz, S, Simon, G, Sydo, T, Vorobcsuk, A, Kiss, R, Toth, K, Szakal, I, Nagy, L, Barany, T, Nagy, A, Szolnoki, E, Mandal, S, Rastogi, V, Shah, B, Mullasari, A, Shankar, J, Mehta, V, Oomman, A, Kaul, U, Komarlu, S, Kahali, D, Bhagwat, A, Vijan, V, Ghaisas, N, Mehta, A, Kashyap, J, Kothari, Y, Taddei, S, Scherillo, M, Zaca, V, Genovese, S, Salvioni, A, Fucili, A, Fedele, F, Cosmi, F, Volpe, M, Mazzone, C, Esposito, G, Doi, M, Yamamoto, H, Sakagami, S, Oishi, S, Yasaka, Y, Tsuboi, H, Fujino, Y, Matsuoka, S, Watanabe, Y, Himi, T, Ide, T, Ichikawa, M, Kijima, Y, Koga, T, Yuda, S, Fukui, K, Kubota, T, Manita, M, Fujinaga, H, Matsumura, T, Fukumoto, Y, Kato, R, Kawai, Y, Hiasa, G, Kazatani, Y, Mori, M, Ogimoto, A, Inoko, M, Oguri, M, Kinoshita, M, Okuhara, K, Watanabe, N, Ono, Y, Otomo, K, Sato, Y, Matsunaga, T, Takaishi, A, Miyagi, N, Uehara, H, Takaishi, H, Urata, H, Kataoka, T, Matsubara, H, Matsumoto, T, Suzuki, T, Takahashi, N, Imamaki, M, Yoshitama, T, Saito, T, Sekino, H, Furutani, Y, Koda, M, Shinozaki, T, Hirabayashi, K, Tsunoda, R, Yonezawa, K, Hori, H, Yagi, M, Arikawa, M, Hashizume, T, Ishiki, R, Koizumi, T, Nakayama, K, Taguchi, S, Nanasato, M, Yoshida, Y, Tsujiyama, S, Nakamura, T, Oku, K, Shimizu, M, Suwa, M, Momiyama, Y, Sugiyama, H, Kobayashi, K, Inoue, S, Kadokami, T, Maeno, K, Kawamitsu, K, Maruyama, Y, Nakata, A, Shibata, T, Wada, A, Cho, H, Na, J, Yoo, B, Choi, J, Hong, S, Shin, J, Cho, M, Han, S, Jeong, J, Kim, J, Kang, S, Kim, D, Kim, M, Llamas Esperon, G, Illescas Diaz, J, Fajardo Campos, P, Almeida Alvarado, J, Bazzoni Ruiz, A, Echeverri Rico, J, Lopez Alcocer, I, Valle Molina, L, Hernandez Herrera, C, Calvo Vargas, C, Padilla Padilla, F, Rodriguez Briones, I, Chuquiure Valenzuela, E, Aguilera Real, M, Carrillo Calvillo, J, Alpizar Salazar, M, Cervantes Escarcega, J, Velasco Sanchez, R, Al - Windy, N, van Heerebeek, L, Bellersen, L, Brunner-La Rocca, H, Post, J, Linssen, G, van de Wetering, M, Peters, R, van Stralen, R, Groutars, R, Smits, P, Yilmaz, A, Kok, W, Van der Meer, P, Dijkmans, P, Troquay, R, van Alem, A, Van de Wal, R, Handoko, L, Westendorp, I, van Bergen, P, Rensing, B, Hoogslag, P, Kietselaer, B, Kragten, J, den Hartog, F, Alings, A, Danilowicz-Szymanowicz, L, Raczak, G, Piesiewicz, W, Zmuda, W, Kus, W, Podolec, P, Musial, W, Drelich, G, Kania, G, Miekus, P, Mazur, S, Janik, A, Spyra, J, Peruga, J, Balsam, P, Krakowiak, B, Szachniewicz, J, Ginel, M, Grzybowski, J, Chrustowski, W, Wojewoda, P, Kalinka, A, Zurakowski, A, Koc, R, Debinski, M, Fil, W, Kujawiak, M, Forys, J, Kasprzak, M, Krol, M, Michalski, P, Mirek-Bryniarska, E, Radwan, K, Skonieczny, G, Stania, K, Skoczylas, G, Madej, A, Jurowiecki, J, Firek, B, Wozakowska-Kaplon, B, Cymerman, K, Neutel, J, Adams, K, Balfour, P, Deswal, A, Djamson, A, Duncan, P, Hong, M, Murray, C, Rinde-Hoffman, D, Woodhouse, S, Macnevin, R, Rama, B, Broome-Webster, C, Kindsvater, S, Abramov, D, Barettella, M, Pinney, S, Herre, J, Cohen, A, Vora, K, Challappa, K, West, S, Baum, S, Cox, J, Jani, S, Karim, A, Akhtar, A, Quintana, O, Paukman, L, Goldberg, R, Bhatti, Z, Budoff, M, Bush, E, Potler, A, Delgado, R, Ellis, B, Dy, J, Fialkow, J, Sangrigoli, R, Ferdinand, K, East, C, Falkowski, S, Donahoe, S, Ebrahimi, R, Kline, G, Harris, B, Khouzam, R, Jaffrani, N, Jarmukli, N, Kazemi, N, Koren, M, Friedman, K, Herzog, W, Silva Enciso, J, Cheung, D, Grover-McKay, M, Hauptman, P, Mikhalkova, D, Hegde, V, Hodsden, J, Khouri, S, Mcgrew, F, Littlefield, R, Bradley, P, Mclaurin, B, Lupovitch, S, Labin, I, Rao, V, Leithe, M, Lesko, M, Lewis, N, Lombardo, D, Mahal, S, Malhotra, V, Dauber, I, Banerjee, A, Needell, J, Miller, G, Paladino, L, Munuswamy, K, Nanna, M, Mcmillan, E, Mumma, M, Napoli, M, Nelson, W, O'Brien, T, Adlakha, A, Onwuanyi, A, Serota, H, Schmedtje, J, Paraschos, A, Potu, R, Sai-Sudhakar, C, Saltzberg, M, Sauer, A, Shah, P, Skopicki, H, Bui, H, Carr, K, Stevens, G, Tahirkheli, N, Tallaj, J, Yousuf, K, Trichon, B, Welker, J, Tolerico, P, Vest, A, Vivo, R, Wang, X, Abadier, R, Dunlap, S, Weintraub, N, Malik, A, Kotha, P, Zaha, V, Kim, G, Uriel, N, Greene, T, Salacata, A, Arora, R, Gazmuri, R, Kobayashi, J, Iteld, B, Vijayakrishnan, R, Dab, R, Mirza, Z, Marques, V, Nallasivan, M, Bensimhon, D, Peart, B, Saint-Jacques, H, Barringhaus, K, Contreras, J, Gupta, A, Koneru, S, Nguyen, V, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
- Subjects
Male ,medicine.medical_specialty ,Angiotensin receptor ,Glucoside ,Endocrinology, Diabetes and Metabolism ,[SDV]Life Sciences [q-bio] ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Adrenergic beta-Antagonists ,Angiotensin-Converting Enzyme Inhibitors ,030204 cardiovascular system & hematology ,Placebo ,03 medical and health sciences ,Angiotensin Receptor Antagonists ,0302 clinical medicine ,Endocrinology ,Mineralocorticoid receptor ,Glucosides ,Double-Blind Method ,Internal medicine ,Post-hoc analysis ,Internal Medicine ,medicine ,Empagliflozin ,Humans ,030212 general & internal medicine ,Benzhydryl Compounds ,ComputingMilieux_MISCELLANEOUS ,Aged ,Benzhydryl Compound ,Heart Failure ,Ejection fraction ,business.industry ,Angiotensin Receptor Antagonist ,Adrenergic beta-Antagonist ,Angiotensin-Converting Enzyme Inhibitor ,Stroke Volume ,medicine.disease ,3. Good health ,Heart failure ,ACE inhibitor ,Female ,Hypotension ,business ,medicine.drug ,Human - Abstract
Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.
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- 2022
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