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

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. Stefansson, Robert D. Toto, Anna Maria Langkilde, David C. Wheeler, Hiddo J.L. Heerspink, David C. Wheeler, Glenn Chertow, Ricardo Correa-Rotter, Tom Greene, Fan Fan HouJohn McMurray, Peter Rossing, Robert Toto, Bergur Stefansson, Anna Maria Langkilde., L. E. Maffei, P. Raffaele, S. E. Solis, C. A. Arias, D. Aizenberg, C. Luquez, C. Zaidman, N. Cluigt, M. Mayer, A. Alvarisqueta, A. Wassermann, R. Maldonado, J. Bittar, M. Maurich, L. E. Gaite, N. Garcia, L. Sivak, P. O. Ramallo, J. C. Santos, R. Garcia Duran, J. A. Oddino, A. Maranon, L. N. Maia, D. D Avila, E. J.G. Barros, M. H. Vidotti, D. Panarotto, I. D.L. Noronha, L. A.A. Turatti, L. Deboni, M. E. Canziani, M. C. Riella, M. R. Bacci, R. P. Paschoalin, R. J. Franco, J. C. Goldani, E. St-Amour, A. W. Steele, R. Goldenberg, S. Pandeya, H. Bajaj, D. Cherney, S. M. Kaiser, J. R. Conway, S. S. Chow, G. Bailey, J. Lafrance, J. Winterstein, S. Cournoyer, D. Gaudet, F. Madore, R. L. Houlden, A. Dowell, M. Langlois, N. Muirhead, H. Khandwala, A. Levin, F. Hou, Y. Xue, L. Zuo, C. Hao, Z. Ni, C. Xing, N. Chen, Y. Dong, R. Zhou, X. Xiao, Y. Zou, C. Wang, B. Liu, Q. Chen, M. Lin, Q. Luo, D. Zhang, J. Wang, M. Chen, X. Wang, A. Zhong, J. Dong, C. Zhu, T. Yan, P. Luo, Y. Ren, P. Pai, D. Li, R. Zhang, J. Zhang, M. Xu, Y. Zhuang, Y. Kong, X. Yao, X. Peng, F. I. Persson, T. K. Hansen, R. Borg, U. Pedersen Bjergaard, D. Hansen, M. Hornum, H. Haller, G. Klausmann, D. Tschope, T. Kruger, P. Gross, C. Hugo, N. Obermuller, L. Rose, P. Mertens, H. Zeller-Stefan, A. Fritsche, L. Renders, J. Muller, K. Budde, B. Schroppel, I. Wittmann, P. Voros, M. Dudas, G. A. Tabak, R. Kirschner, A. Letoha, I. Balku, Z. Hermanyi, G. Zakar, I. Mezei, G. G. Nagy, J. Lippai, A. Nemeth, D. Khullar, P. K. Gowdaiah, E. Fernando Mervin, V. A. Rao, D. Dewan, V. S.K. Maddi, M. S. Vyawahare, R. K. Pulichikkat, S. K. Sonkar, V. K. Gupta, S. Agarwal, A. J. Asirvatham, A. Ignatius, S. Chaubey, S. Melemadathil, H. Alva, Y. Kadam, H. Shimizu, A. Sueyoshi, H. Takeoka, Y. Abe, T. Imai, Y. Onishi, Y. Fujita, Y. Tokita, Y. Makita, A. Idogaki, R. Koyama, H. Kikuchi, N. Kashihara, T. Hayashi, Y. Ando, T. Tanaka, M. Shimizu, S. Hidaka, T. Gohda, K. Tamura, M. Abe, Y. Kamijo, T. Imasawa, Y. Takahashi, M. Nakayama, M. Tomita, F. Hirano, M. Nakayama, Y. Fukushima, A. Kiyosue, S. Kurioka, E. Imai, K. Kitagawa, M. Waki, J. Wada, K. Uehara, H. Iwatani, K. Ota, S. Shibazaki, K. Tamura, K. Katayama, I. Narita, M. Iinuma, S. Matsueda, S. Sasaki, A. Yokochi, T. Tsukamoto, T. Yoshimura, S. Kang, S. Lee, C. S. Lim, H. Chin, K. W. Joo, S. Y. Han, T. I. Chang, S. Park, H. Park, C. W. Park, B. G. Han, D. R. Cha, S. A. Yoon, W. Kim, S. W. Kim, D. Ryu, R. Correa Rotter, S. S. Irizar Santana, G. Hernandez Llamas, R. Valdez Ortiz, N. C. Secchi Nicolas, G. Gonzalez Galvez, J. R. Lazcano Soto, T. Bochicchio Riccardelli, E. A. Bayram Llamas, D. R. Ramos Ibarra, M. G.S. Melo, J. G. Gonzalez Gonzalez, J. H. Sanchez Mijangos, M. Madero Robalo, A. Garcia Castillo, H. A. Manrique, J. C. Farfan, R. Vargas, A. Valdivia, A. Dextre, E. Escudero, J. R. Calderon Ticona, L. Gonzales, J. Villena, L. Leon, G. Molina, A. Saavedra, E. Garrido, H. Arbanil, S. Vargas Marquez, J. Rodriguez, R. Isidto, A. J. Villaflor, M. A. Gumba, L. Tirador, R. S. Comia, R. A. Sy, M. L.V.V. Guanzon, G. Aquitania, N. C. De Asis, A. A. Silva, M. E. Lim, R. A. Danguilan, M. Nowicki, H. Rudzki, K. Landa, I. Kucharczyk-Bauman, B. Gogola-Migdal, M. Golski, A. Olech-Cudzik, T. Stompor, T. Szczepanik, B. Miklaszewicz, R. Sciborski, M. Kuzniewski, K. Ciechanowski, D. Wronska, W. Klatko, S. Mazur, G. Popenda, M. Myslicki, L. Z. Bolieva, S. Berns, A. Galyavich, T. Abissova, I. Karpova, D. Platonov, N. Koziolova, L. Kvitkova, R. Nilk, T. Medina, A. Rebrov, M. Rossovskaya, I. Sinitsina, E. Vishneva, N. Zagidullin, T. Novikova, N. Krasnopeeva, O. Magnitskaya, N. Antropenko, M. Batiushin, V. Escudero Quesada, C. Barrios Barrea, E. Espinel Garauz, J. M. Cruzado Garrit, C. Morales Portillo, J. L. Gorriz Teruel, S. Cigarran Guldris, M. Praga Terente, N. R. Robles Perez-Monteoliva, H. Infanta Cristina, F. J. Tinahones Madueno, A. Soto Gonzalez, C. DIaz Rodriguez, H. Furuland, A. Saeed, K. Dreja, J. Spaak, A. Bruchfeld, M. Kolesnyk, O. Levchenko, N. Pyvovarova, V. Stus, V. Doretskyy, N. Korobova, O. Horoshko, I. Katerenchuk, Y. M. Mostovoy, M. Orynchak, O. Legun, I. Dudar, O. Bilchenko, S. Andreychyn, A. Levchenko, L. Zub, N. Tereshchenko, I. Topchii, T. Ostapenko, S. Bezuglova, M. Kopytsya, O. Turenko, P. Mark, J. Barratt, S. Bhandari, D. Fraser, P. Kalra, S. P. Kon, K. McCafferty, A. Mikhail, S. P. Kon, O. P. Alvarado, R. Anderson, N. S. Andrawis, A. Arif, S. A. Benjamin, G. Bueso, R. S. Busch, K. W. Carr, K. W. Carr, P. Crawford, N. Daboul, G. M. De La Calle, B. Delgado, J. Earl, M. A. El-Shahawy, R. J. Graf, G. Greenwood, A. Guevara, E. M. Wendland, R. K. Mayfield, M. Montero, D. J. Morin, P. Narayan, V. Numrungroad, A. C. Reddy, R. Reddy, M. B. Samson, R. Trejo, M. B. Butcher, J. K. Wise, L. R. Zemel, M. Raikhel, D. Weinstein, P. Hernandez, A. Wynne, B. V. Khan, G. A. Sterba, A. Jamal, D. Ross, S. F. Rovner, A. Tan, F. Ovalle, R. J. Patel, J. Talano, D. R. Patel, A. Burgner, N. Aslam, M. Elliott, S. Goral, A. Jovanovich, K. Umanath, D. Waguespack, D. Weiner, M. Yu, L. Schneider, T. Le, N. Nguyen, H. Nguyen, D. Nguyen, V. Nguyen, T. Do, P. Chu, D. Ta, N. Tran, D. Nguyen, Marc A. Pfeffer, Stuart Pocock, Karl Swedberg, Jean L. Rouleau, Nishi Chaturvedi, Peter Ivanovich, Andrew S. Levey, Claes Held, Christina Christersson, Johannes Mann, Christoph Varenhorst

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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) 200–5000mg/g and an estimated glomerular filtration rate (eGFR) 25–75mL/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.

Original languageEnglish (US)
Pages (from-to)1216-1227
Number of pages12
JournalEuropean heart journal
Volume42
Issue number13
DOIs
StatePublished - Apr 1 2021

Keywords

  • Chronic kidney disease
  • Dapagliflozin
  • SGLT2 inhibitor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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