Effects of dapagliflozin on mortality in patients with chronic kidney disease: a pre-specified analysis from the DAPA-CKD randomized controlled trial

著者: Hiddo J.L. Heerspink, C. David Sjöström, Niels Jongs, Glenn M. Chertow, Mikhail Kosiborod, Fan Fan Hou, John J.V. McMurray, Peter Rossing, Ricardo Correa‐Rotter, Raisa Kurlyandskaya, Bergur V. Stefánsson, Robert D. Toto, Anna Maria Langkilde, David C. Wheeler, Hiddo J.L. Heerspink, David C. Wheeler, Glenn M. Chertow, Ricardo Correa‐Rotter, Tom Greene, Fan Fan Hou, John J.V. McMurray, Peter Rossing, Robert D. Toto, Bergur V. Stefánsson, Anna Maria Langkilde, Laura Maffei, Pablo Raffaele, S. Solís, César A. Arias, Dov Aizenberg, Carolina Lúquez, Cesar Javier Zaidman, Natalia Cluigt, M. Mayer, A Alvarisqueta, A. Wassermann, Rafaël Maldonado, J. Bittar, M. Maurich, L.E. Gaite, Nicole Garcia, Leonardo Sivak, Pablo Ramallo, Juan Carlos Santos, Ruben Garcia Duran, Juan Oddino, A Marañón, Lília Nigro Maia, Dánae Duana Ávila, Elvino Barros, Maria H Vidotti, Daniel Panarotto, Irene de Lourdes Noronha, Luiz Alberto Andreotti Turatti, Luciane Mônica Deboni, María Eugênia Fernandes Canziani, Miguel C. Riella, Marcelo Rodrigues Bacci, Raphael Paschoalin, R. J. Franco, João Carlos Goldani, Eric St-Amour, Ann Steele, Ronald Goldenberg, S.B. Pandeya, Harpreet S. Bajaj, David Z.I. Cherney, Stéphanie Kaiser, James Conway, Sharron Chow, G.S. Bailey, Jean‐Philippe Lafrance, Jonathan Winterstein, Serge Cournoyer, Daniel Gaudet, F. Madore, Robyn L. Houlden, Ashley Dowell, Michel R. Langlois, Nicola Muirhead, Hasnain Khandwala, Anna S. Levin, Fan Fan Hou, Ying Xue, Zuo Li, Chuan‐Ming Hao, Zhaohui Ni, C Xing, N Chen, Yugang Dong, Rong Zhou, Xiao Xu, Yiping Zou, Chu Wang, Liu B, Qian Chen, Miao Lin, Qin Luo, David Zhang, Jing Wang, Meng Chen, X Wang, Aihua Zhong, Jun Dong, Chunyan Zhu, T Yan, Ping Luo, Y Ren, Pearl Pai, D. LI, R Zhang, Jian Zhang, Meiling Xu, Yongze Zhuang, Yaozhong Kong, Xin Yao, Xiaomei Peng, Frederik Persson, Troels Krarup Hansen, Rikke Borg, Ulrik Pedersen‐Bjergaard, Dorte Hansen, Mads Hornum, Hermann Haller, Gerhard Klausmann, Diethelm Tschöpe, Thinus F. Kruger, Peter L. Gross, Christian Hugo, Nicholas Obermüller, Ludger Rose, Patrick Mertens, Helga Zeller-Stefan, Andreas Fritsche, Lutz Renders, J Müller, Klemens Budde, Bernd Schröppel, István Wittmann, Péter Vörös, M Dudas, Ádám G. Tabák, Róbert Kirschner, Annamária Letoha, I. Balku, Zs. Hermányi, Gábor Zakar, I Mezei, Gergely Nagy, J Lippai, Andrea H. Németh, Dinesh Khullar, Prakash Kikkeri Gowdaiah, Edwin Fernando Mervin, V. Rao, D. Dewan, Vatsalya Maddi, Milind Vyawahare, Rakesh Pulichikkat, Satyendra Kumar Sonkar, Vivek Gupta, Samarth Agarwal, Arthur Asirvatham, Anita Ignatius, Sanjay Chaubey, Sreelatha Melemadathil, H. Alva, Y. Kadam, Hiroaki Shimizu, A Sueyoshi, Hiroaki Takeoka, Yuko Abe, Takumi Imai, Yukiko Onishi, Yasuko Fujita, Yukichi Tokita, Y Makita, A. Idogaki, Ryo Koyama, H Kikuchi, Naoki Kashihara, Toshimasa Hayashi, Yukio Ando, Tsuyoshi Tanaka, Motohiro Shimizu, Sumi Hidaka, Tomohito Gohda, Kouichi Tamura, Masami Abe, Yoshito Kamijo, Toshiyuki Imasawa, Yasunori Takahashi, Mikihiro Nakayama, Masayoshi Tomita, F. Hirano, Mikihiro Nakayama, Yasushi Fukushima, Arihiro Kiyosue, Sumiko Kurioka, Eri Imai, Kazuo Kitagawa, Masako Waki, Jun Wada, K. Uehara, Hirotsugu Iwatani, Keiko Ota, Satomi Shibazaki, Kouichi Tamura, Kan Katayama, Ichiei Narita, Masahiro Iinuma, Satoko Matsueda, Shoji Sasaki, Alex Yokochi, Tatsuo Tsukamoto, Teizo Yoshimura, Soyoung Kang, S Lee, Chun Soo Lim, Ho Jun Chin, Kwon Wook Joo, Suji Han, Tara I. Chang, Soo-Hyun Park, Hyunmi Park, C W Park, Bin Han, D R Cha, Sung-Sik Yoon, Won Jung Kim, Suck Won Kim, Dongsu Ryu, R Correa Rotter, Sergio Saul Irizar Santana, G. Hernandez Llamas, R Valdez Ortiz, N. Nicolas, Guillermo González-Gálvez, José Roberto Lazcano Soto, T. Bochicchio Riccardelli, E Llamas, Denisse Ramos Ibarra, Maira Gabrielle Silva Melo, José Gerardo González‐González, Jose Hector Sanchez Mijangos, Margarida Robalo, Armando García Castillo, Hélard Manrique, J. Farfan, Ramón Vargas, Alicia Valdivia, A. Dextre, Elizabeth Escudero, Jorge R Calderon Ticona, Liberty Gonzales, Jaime E. Villena, L Leon, Guilherme Eckhardt Molina, Alene Saavedra, Emanuel Pimenta Garrido, Hugo Arbañil, Sofia Marquez, J Rodriguez, Rey Isidto, Agnes Jeans Villaflor, M.A. Gumba, Louie Tirador, Rhea Severina Comia, Rosa Allyn Sy, Mitchell Guanzon, Grace Aquitania, Norman Cornelio De Asis, A A Silva, Maggie Lim, Romina A. Danguilan, Michał Nowicki, H Rudzki, Karenia Landa, Izabela Kucharczyk-Bauman, B. Gogola-Migdal, M. Golski, Anna Olech-Cudzik, Tomasz Stompór, T. Szczepanik, B Miklaszewicz, R Ściborski, Marek Kuźniewski, Kazimierz Ciechanowski, Danuta Wrońska, Wiesław Klatko, Stanisław Mazur, Grazyna Popenda, Marcin Myślicki, Л. З. Болиева, Stefanie Berns, А. S. Galyavich, Т. О. Абиссова, I. S. Karpova, D. Yu. Platonov, Н. А. Козиолова, Liudmila Kvitkova, Rostislav Nilk, Theresa Medina, А. П. Ребров, M. Rossovskaya, Irina Sinitsina, Еlena A. Vishneva, Н. Ш. Загидуллин, Т. И. Новикова, N Krasnopeeva, O. V. Magnitskaya, Natalia Antropenko, М. М. Батюшин, Verónica Escudero Quesada, Christophe Barrea, E. Espinel Garauz, Josep María Cruzado Garrit, C Morales Portillo, J.L. Teruel, Secundino Cigarrán, Manuel Praga Terente, Nicolas-Roberto Robles Perez-Monteoliva, Helen Cristina, F J Tinahones Madueno, Alfonso González, Claudia Rodríguez, Hans Furuland, Abdallah Saeed, Karl Dreja, Jonas Spaak, Annette Bruchfeld, М. Kolesnyk, Olena Levchenko, N. Pyvovarova, V.P. Stus, V. Doretskyy, N. Korobova, Olha Horoshko, І. П. Катеренчук, Yuriy Mostovoy, Mariya A. Orynchak, Oleg Legun, І. Dudar, Oleksandr Bilchenko, S. M. Аndreychyn, Andre Levchenko, Л.О. Зуб, N. M. Tereshchenko, И. И. Топчий, T. Ostapenko, S Bezuglova, Mykola Kopytsya, O. Turenko, Patrick B. Mark, Jonathan Barratt, Sudhir Bhandari, Donald Fraser, P A Kalra, Soichiro Kon, Kieran McCafferty, Ashraf Mikhail, Soichiro Kon, Odilon Alvarado, Ronald Anderson, Nabil Andrawis, Ahmed A. Arif, S.A. Benjamin, Gonzalo Carles Bueso, Robert S. Busch, Keith Carr, Kenneth W Carr, Paul Crawford, Nizar Daboul, Germán Calle, Bruno Delgado, Judith Earl, M. El-Shahawy, Ronald J. Graf, Gemma K. Greenwood, A Guevara, Eliana Wendland, Ronald K. Mayfield, M. Montero, Diane Morin, Perinchery Narayan, Visal Numrungroad, Arthi Reddy, K. Rajender Reddy, Mercedes B. Samson, R. A. Trejo, Michelle Butcher, Jacqui Wise, L.R. Zemel, Marina Raikhel, D. Weinstein, Pilar Hernández, A. M. Wynne, Bobby V. Khan, Gary Sterba, Aziz Jamal, Dennis L. Ross, Sergio Rovner, Anjanette Tan, Fernando Ovalle, Rajesh Patel, Julie‐An Talano, Dilip R. Patel, Anna Burgner, Nabeel Aslam, Mark A. Elliott, Simin Göral, Anna Jovanovich, Kausik Umanath, Dia R. Waguespack, Daniel Weiner, Margaret K. Yu, Lynda C. Schneider, Trang T. Le, Toshiyoshi Fujiwara M.D., Ninh T. Nguyen, Hai V. Nguyen, Deanna D. Nguyen, Vincent Nguyen, T Do, Pao‐Hsien Chu, D. Ta, Ngoc Huu Tran, Deanna D. Nguyen, Marc A. Pfeffer, Stuart Pocock, Karl Swedberg, Jean L. Rouleau, Nish Chaturvedi, Peter Ivanovich, Andrew S. Levey, Claes Held, Christina Christersson, Johannes F.E. Mann, Christoph Varenhorst - European Heart Journal 2021 被引用: 122

AIMS: Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death. METHODS AND RESULTS: DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo. CONCLUSION: In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.