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. 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
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) 200-5000 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.