抄録
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.
| 本文言語 | English |
|---|---|
| ページ（範囲） | 1216-1227 |
| ページ数 | 12 |
| ジャーナル | European Heart Journal |
| 巻 | 42 |
| 号 | 13 |
| DOI | |
| 出版ステータス | Published - 2021 4月 1 |
| 外部発表 | はい |
ASJC Scopus subject areas
- 循環器および心血管医学
フィンガープリント
「Effects of dapagliflozin on mortality in patients with chronic kidney disease: A pre-specified analysis from the DAPA-CKD randomized controlled trial」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。引用スタイル
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
In: European Heart Journal, Vol. 42, No. 13, 01.04.2021, p. 1216-1227.
研究成果: Article › 査読
}
TY - JOUR
T1 - Effects of dapagliflozin on mortality in patients with chronic kidney disease
T2 - A pre-specified analysis from the DAPA-CKD randomized controlled trial
AU - Heerspink, Hiddo J.L.
AU - Sjöström, C. David
AU - Jongs, Niels
AU - Chertow, Glenn M.
AU - Kosiborod, Mikhail
AU - Hou, Fan Fan
AU - McMurray, John J.V.
AU - Rossing, Peter
AU - Correa-Rotter, Ricardo
AU - Kurlyandskaya, Raisa
AU - Stefansson, Bergur V.
AU - Toto, Robert D.
AU - Langkilde, Anna Maria
AU - Wheeler, David C.
AU - Heerspink, Hiddo J.L.
AU - Wheeler, David C.
AU - Chertow, Glenn
AU - Correa-Rotter, Ricardo
AU - Greene, Tom
AU - McMurray, John
AU - Rossing, Peter
AU - Toto, Robert
AU - Stefansson, Bergur
AU - Maria Langkilde., Anna
AU - Maffei, L. E.
AU - Raffaele, P.
AU - Solis, S. E.
AU - Arias, C. A.
AU - Aizenberg, D.
AU - Luquez, C.
AU - Zaidman, C.
AU - Cluigt, N.
AU - Mayer, M.
AU - Alvarisqueta, A.
AU - Wassermann, A.
AU - Maldonado, R.
AU - Bittar, J.
AU - Maurich, M.
AU - Gaite, L. E.
AU - Garcia, N.
AU - Sivak, L.
AU - Ramallo, P. O.
AU - Santos, J. C.
AU - Garcia Duran, R.
AU - Oddino, J. A.
AU - Maranon, A.
AU - Maia, L. N.
AU - D Avila, D.
AU - Barros, E. J.G.
AU - Vidotti, M. H.
AU - Panarotto, D.
AU - Noronha, I. D.L.
AU - Turatti, L. A.A.
AU - Deboni, L.
AU - Canziani, M. E.
AU - Riella, M. C.
AU - Bacci, M. R.
AU - Paschoalin, R. P.
AU - Franco, R. J.
AU - Goldani, J. C.
AU - St-Amour, E.
AU - Steele, A. W.
AU - Goldenberg, R.
AU - Pandeya, S.
AU - Bajaj, H.
AU - Cherney, D.
AU - Kaiser, S. M.
AU - Conway, J. R.
AU - Chow, S. S.
AU - Bailey, G.
AU - Lafrance, J.
AU - Winterstein, J.
AU - Cournoyer, S.
AU - Gaudet, D.
AU - Madore, F.
AU - Houlden, R. L.
AU - Dowell, A.
AU - Langlois, M.
AU - Muirhead, N.
AU - Khandwala, H.
AU - Levin, A.
AU - Xue, Y.
AU - Zuo, L.
AU - Hao, C.
AU - Ni, Z.
AU - Xing, C.
AU - Chen, N.
AU - Dong, Y.
AU - Zhou, R.
AU - Xiao, X.
AU - Zou, Y.
AU - Wang, C.
AU - Liu, B.
AU - Chen, Q.
AU - Lin, M.
AU - Luo, Q.
AU - Zhang, D.
AU - Wang, J.
AU - Chen, M.
AU - Wang, X.
AU - Zhong, A.
AU - Dong, J.
AU - Zhu, C.
AU - Yan, T.
AU - Luo, P.
AU - Ren, Y.
AU - Pai, P.
AU - Li, D.
AU - Zhang, R.
AU - Zhang, J.
AU - Xu, M.
AU - Zhuang, Y.
AU - Kong, Y.
AU - Yao, X.
AU - Peng, X.
AU - Persson, F. I.
AU - Hansen, T. K.
AU - Borg, R.
AU - Pedersen Bjergaard, U.
AU - Hansen, D.
AU - Hornum, M.
AU - Haller, H.
AU - Klausmann, G.
AU - Tschope, D.
AU - Kruger, T.
AU - Gross, P.
AU - Hugo, C.
AU - Obermuller, N.
AU - Rose, L.
AU - Mertens, P.
AU - Zeller-Stefan, H.
AU - Fritsche, A.
AU - Renders, L.
AU - Muller, J.
AU - Budde, K.
AU - Schroppel, B.
AU - Wittmann, I.
AU - Voros, P.
AU - Dudas, M.
AU - Tabak, G. A.
AU - Kirschner, R.
AU - Letoha, A.
AU - Balku, I.
AU - Hermanyi, Z.
AU - Zakar, G.
AU - Mezei, I.
AU - Nagy, G. G.
AU - Lippai, J.
AU - Nemeth, A.
AU - Khullar, D.
AU - Gowdaiah, P. K.
AU - Fernando Mervin, E.
AU - Rao, V. A.
AU - Dewan, D.
AU - Maddi, V. S.K.
AU - Vyawahare, M. S.
AU - Pulichikkat, R. K.
AU - Sonkar, S. K.
AU - Gupta, V. K.
AU - Agarwal, S.
AU - Asirvatham, A. J.
AU - Ignatius, A.
AU - Chaubey, S.
AU - Melemadathil, S.
AU - Alva, H.
AU - Kadam, Y.
AU - Shimizu, H.
AU - Sueyoshi, A.
AU - Takeoka, H.
AU - Abe, Y.
AU - Imai, T.
AU - Onishi, Y.
AU - Fujita, Y.
AU - Tokita, Y.
AU - Makita, Y.
AU - Idogaki, A.
AU - Koyama, R.
AU - Kikuchi, H.
AU - Kashihara, N.
AU - Hayashi, T.
AU - Ando, Y.
AU - Tanaka, T.
AU - Shimizu, M.
AU - Hidaka, S.
AU - Gohda, T.
AU - Tamura, K.
AU - Abe, M.
AU - Kamijo, Y.
AU - Imasawa, T.
AU - Takahashi, Y.
AU - Nakayama, M.
AU - Tomita, M.
AU - Hirano, F.
AU - Nakayama, M.
AU - Fukushima, Y.
AU - Kiyosue, A.
AU - Kurioka, S.
AU - Imai, E.
AU - Kitagawa, K.
AU - Waki, M.
AU - Wada, J.
AU - Uehara, K.
AU - Iwatani, H.
AU - Ota, K.
AU - Shibazaki, S.
AU - Tamura, K.
AU - Katayama, K.
AU - Narita, I.
AU - Iinuma, M.
AU - Matsueda, S.
AU - Sasaki, S.
AU - Yokochi, A.
AU - Tsukamoto, T.
AU - Yoshimura, T.
AU - Kang, S.
AU - Lee, S.
AU - Lim, C. S.
AU - Chin, H.
AU - Joo, K. W.
AU - Han, S. Y.
AU - Chang, T. I.
AU - Park, S.
AU - Park, H.
AU - Park, C. W.
AU - Han, B. G.
AU - Cha, D. R.
AU - Yoon, S. A.
AU - Kim, W.
AU - Kim, S. W.
AU - Ryu, D.
AU - Correa Rotter, R.
AU - Irizar Santana, S. S.
AU - Hernandez Llamas, G.
AU - Valdez Ortiz, R.
AU - Secchi Nicolas, N. C.
AU - Gonzalez Galvez, G.
AU - Lazcano Soto, J. R.
AU - Bochicchio Riccardelli, T.
AU - Bayram Llamas, E. A.
AU - Ramos Ibarra, D. R.
AU - Melo, M. G.S.
AU - Gonzalez Gonzalez, J. G.
AU - Sanchez Mijangos, J. H.
AU - Madero Robalo, M.
AU - Garcia Castillo, A.
AU - Manrique, H. A.
AU - Farfan, J. C.
AU - Vargas, R.
AU - Valdivia, A.
AU - Dextre, A.
AU - Escudero, E.
AU - Calderon Ticona, J. R.
AU - Gonzales, L.
AU - Villena, J.
AU - Leon, L.
AU - Molina, G.
AU - Saavedra, A.
AU - Garrido, E.
AU - Arbanil, H.
AU - Vargas Marquez, S.
AU - Rodriguez, J.
AU - Isidto, R.
AU - Villaflor, A. J.
AU - Gumba, M. A.
AU - Tirador, L.
AU - Comia, R. S.
AU - Sy, R. A.
AU - Guanzon, M. L.V.V.
AU - Aquitania, G.
AU - De Asis, N. C.
AU - Silva, A. A.
AU - Lim, M. E.
AU - Danguilan, R. A.
AU - Nowicki, M.
AU - Rudzki, H.
AU - Landa, K.
AU - Kucharczyk-Bauman, I.
AU - Gogola-Migdal, B.
AU - Golski, M.
AU - Olech-Cudzik, A.
AU - Stompor, T.
AU - Szczepanik, T.
AU - Miklaszewicz, B.
AU - Sciborski, R.
AU - Kuzniewski, M.
AU - Ciechanowski, K.
AU - Wronska, D.
AU - Klatko, W.
AU - Mazur, S.
AU - Popenda, G.
AU - Myslicki, M.
AU - Bolieva, L. Z.
AU - Berns, S.
AU - Galyavich, A.
AU - Abissova, T.
AU - Karpova, I.
AU - Platonov, D.
AU - Koziolova, N.
AU - Kvitkova, L.
AU - Nilk, R.
AU - Medina, T.
AU - Rebrov, A.
AU - Rossovskaya, M.
AU - Sinitsina, I.
AU - Vishneva, E.
AU - Zagidullin, N.
AU - Novikova, T.
AU - Krasnopeeva, N.
AU - Magnitskaya, O.
AU - Antropenko, N.
AU - Batiushin, M.
AU - Escudero Quesada, V.
AU - Barrios Barrea, C.
AU - Espinel Garauz, E.
AU - Cruzado Garrit, J. M.
AU - Morales Portillo, C.
AU - Gorriz Teruel, J. L.
AU - Cigarran Guldris, S.
AU - Praga Terente, M.
AU - Robles Perez-Monteoliva, N. R.
AU - Infanta Cristina, H.
AU - Tinahones Madueno, F. J.
AU - Soto Gonzalez, A.
AU - DIaz Rodriguez, C.
AU - Furuland, H.
AU - Saeed, A.
AU - Dreja, K.
AU - Spaak, J.
AU - Bruchfeld, A.
AU - Kolesnyk, M.
AU - Levchenko, O.
AU - Pyvovarova, N.
AU - Stus, V.
AU - Doretskyy, V.
AU - Korobova, N.
AU - Horoshko, O.
AU - Katerenchuk, I.
AU - Mostovoy, Y. M.
AU - Orynchak, M.
AU - Legun, O.
AU - Dudar, I.
AU - Bilchenko, O.
AU - Andreychyn, S.
AU - Levchenko, A.
AU - Zub, L.
AU - Tereshchenko, N.
AU - Topchii, I.
AU - Ostapenko, T.
AU - Bezuglova, S.
AU - Kopytsya, M.
AU - Turenko, O.
AU - Mark, P.
AU - Barratt, J.
AU - Bhandari, S.
AU - Fraser, D.
AU - Kalra, P.
AU - Kon, S. P.
AU - McCafferty, K.
AU - Mikhail, A.
AU - Kon, S. P.
AU - Alvarado, O. P.
AU - Anderson, R.
AU - Andrawis, N. S.
AU - Arif, A.
AU - Benjamin, S. A.
AU - Bueso, G.
AU - Busch, R. S.
AU - Carr, K. W.
AU - Carr, K. W.
AU - Crawford, P.
AU - Daboul, N.
AU - De La Calle, G. M.
AU - Delgado, B.
AU - Earl, J.
AU - El-Shahawy, M. A.
AU - Graf, R. J.
AU - Greenwood, G.
AU - Guevara, A.
AU - Wendland, E. M.
AU - Mayfield, R. K.
AU - Montero, M.
AU - Morin, D. J.
AU - Narayan, P.
AU - Numrungroad, V.
AU - Reddy, A. C.
AU - Reddy, R.
AU - Samson, M. B.
AU - Trejo, R.
AU - Butcher, M. B.
AU - Wise, J. K.
AU - Zemel, L. R.
AU - Raikhel, M.
AU - Weinstein, D.
AU - Hernandez, P.
AU - Wynne, A.
AU - Khan, B. V.
AU - Sterba, G. A.
AU - Jamal, A.
AU - Ross, D.
AU - Rovner, S. F.
AU - Tan, A.
AU - Ovalle, F.
AU - Patel, R. J.
AU - Talano, J.
AU - Patel, D. R.
AU - Burgner, A.
AU - Aslam, N.
AU - Elliott, M.
AU - Goral, S.
AU - Jovanovich, A.
AU - Umanath, K.
AU - Waguespack, D.
AU - Weiner, D.
AU - Yu, M.
AU - Schneider, L.
AU - Le, T.
AU - Nguyen, N.
AU - Nguyen, H.
AU - Nguyen, D.
AU - Nguyen, V.
AU - Do, T.
AU - Chu, P.
AU - Ta, D.
AU - Tran, N.
AU - Nguyen, D.
AU - Pfeffer, Marc A.
AU - Pocock, Stuart
AU - Swedberg, Karl
AU - Rouleau, Jean L.
AU - Chaturvedi, Nishi
AU - Ivanovich, Peter
AU - Levey, Andrew S.
AU - Held, Claes
AU - Christersson, Christina
AU - Mann, Johannes
AU - Varenhorst, Christoph
N1 - Funding Information: Conflict of interest: H.J.L.H. has received support from AstraZeneca to his institution for the DAPA-CKD trial; fees to his institution for his participation in advisory boards for Merck, Mitsubishi Tanabe, Janssen, and Mundipharma; as a consultant for AbbVie, Retrophin, Boehringer Ingelheim, and Novo Nordisk; for participation in steering committees for Janssen, Gilead, Bayer, Chinook, and CSL Pharma; and research support from AbbVie, AstraZeneca, Boehringer Ingelheim, and Janssen. N.J. has no conflicts of interest to declare. G.M.C. has received fees from AstraZeneca for the DAPA-CKD trial steering committee and research grants from NIDDK and Amgen; he is on the board of directors for Satellite Healthcare, has received fees for advisory boards for Ardelyx, Baxter, Cloud Cath, Cricket, Dia Medica, Durect, DxNow, Outset, and Reata, holds stock options for Ardelyx, CloudCath, Durect, DxNow, and Outset, has received fees from Akebia, Gilead, Sanifit, and Vertex for trial steering committees, and has received fees for DSMB service from Angion, Bayer, and ReCor. F.F.H. has received honoraria from AstraZeneca as a member of the executive member of the DAPA-CKD study and received honoraria from AbbVie for participation in a steering committee. J.J.V.M. has received support to his institution, Glasgow University, for work on clinical trials, consulting, and other activities: Abbvie, Alnylam, Amgen, AstraZeneca, Bayer, BMS, Cardurion, Cyclerion, Cytokinetics, DalCor, GSK, Kidney Research UK, Merck, Novartis, Pfizer, Servier, Theracos, and Vifor Fresenius. He has received personal lecture fees: Abbott, Hickman, Sun Pharmaceuticals, and Servier. R.C-R. has received fees from AstraZeneca for the DAPA-CKD trial steering committee; speaker fees from Boehringer Ingelheim, Amgen, and Janssen; research support from GlaxoSmithKline and Novo Nordisk; and honoraria for advisory boards from Boehringer Ingelheim, Novo Nordisk, and Medtronic. M.K. has served as consultant for Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Merck (Diabetes), Novo Nordisk, Sanofi, and Vifor Pharma. He received research grants from AstraZeneca and Boehringer Ingelheim. P.R. has received fees to his institution for research support from AstraZeneca and Novo Nordisk; for steering group participation from AstraZeneca, Gilead, Novo Nordisk, and Bayer; for lectures from Bayer, Eli Lilly, and Novo Nordisk; and for advisory boards from Sanofi and Boehringer Ingelheim. R.D.T. has received support from AstraZeneca as a member of the executive committee for DAPA-CKD; is a consultant for Boehringer Ingelheim; has participated on advisory boards for Bayer and Relypsa; and served on data monitoring committees for Akebia and Reata Pharmaceuticals, executive committee for Amgen, and as a faculty associate for Quest Diagnostics. R.K., B.V.S., C.D.S., and A.M.L. are employees and stockholders of AstraZeneca. D.C.W. provides ongoing consultancy services to AstraZeneca and has received honoraria and/or consultancy fees from Amgen, Astellas, Boehringer Ingelheim, Bayer, GlaxoSmithKline, Janssen, Napp, Mundipharma, Merck Sharp and Dohme, Reata, Tricida, and Vifor Fresenius. Publisher Copyright: © The Author(s), 2021.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - 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.
AB - 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.
KW - Chronic kidney disease
KW - Dapagliflozin
KW - SGLT2 inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85103743786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103743786&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehab094
DO - 10.1093/eurheartj/ehab094
M3 - Article
C2 - 33792669
AN - SCOPUS:85103743786
SN - 0195-668X
VL - 42
SP - 1216
EP - 1227
JO - European Heart Journal
JF - European Heart Journal
IS - 13
ER -