Dapagliflozin in Patients with Chronic Kidney Disease

被引：3804

作者：

Heerspink, Hiddo J. L. ^{[1
,2
]}

Stefansson, Bergur V. ^{[3
]}

Correa-Rotter, Ricardo ^{[4
]}

Chertow, Glenn M. ^{[5
,6
,7
]}

Greene, Tom ^{[8
]}

Hou, Fan-Fan ^{[9
]}

Mann, Johannes F. E. ^{[10
,11
]}

McMurray, John J. V. ^{[12
]}

Lindberg, Magnus ^{[3
]}

Rossing, Peter ^{[14
,15
]}

Sjostrom, C. David ^{[3
]}

Toto, Roberto D. ^{[16
]}

Langkilde, Anna-Maria ^{[3
]}

Wheeler, David C. ^{[2
,13
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands

[2] George Inst Global Hlth, Sydney, NSW, Australia

[3] AstraZeneca, BioPharmaceut R&D, Late Stage Dev Cardiovasc Renal & Metab, Gothenburg, Sweden

[4] Natl Med Sci & Nutr Inst Salvador Zubiran, Mexico City, DF, Mexico

[5] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA

[6] Stanford Univ, Sch Med, Dept Epidemiol, Stanford, CA 94305 USA

[7] Stanford Univ, Sch Med, Dept Populat Hlth, Stanford, CA 94305 USA

[8] Univ Utah Hlth Sci, Study Design & Biostat Ctr, Salt Lake City, UT USA

[9] Southern Med Univ, Nanfang Hosp, Div Nephrol, Natl Clin Res Ctr Kidney Dis, Guangzhou, Peoples R China

[10] KfH Kidney Ctr, Munich, Germany

[11] Univ Erlangen Nurnberg, Dept Med 4, Erlangen, Germany

[12] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland

[13] UCL, Dept Renal Med, London, England

[14] Steno Diabet Ctr Copenhagen, Gentofte, Denmark

[15] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark

[16] UT Southwestern Med Ctr, Dept Internal Med, Dallas, TX USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2020年 / 383卷 / 15期

关键词：

CARDIOVASCULAR OUTCOMES; EMPAGLIFLOZIN;

D O I：

10.1056/NEJMoa2024816

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known. METHODS We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m(2) of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes. RESULTS The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P=0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P=0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed. CONCLUSIONS Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo.

引用

页码：1436 / 1446

页数：11

共 20 条

[1]

Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 [J].

Bikbov, Boris ;

Purcell, Carrie ;

Levey, Andrew S. ;

Smith, Mari ;

Abdoli, Amir ;

Abebe, Molla ;

Adebayo, Oladimeji M. ;

Afarideh, Mohsen ;

Agarwal, Sanjay Kumar ;

Agudelo-Botero, Marcela ;

Ahmadian, Elham ;

Al-Aly, Ziyad ;

Alipour, Vahid ;

Almasi-Hashiani, Amir ;

Al-Raddadi, Rajaa M. ;

Alvis-Guzman, Nelson ;

Amini, Saeed ;

Andrei, Tudorel ;

Andrei, Catalina Liliana ;

Andualem, Zewudu ;

Anjomshoa, Mina ;

Arabloo, Jalal ;

Ashagre, Alebachew Fasil ;

Asmelash, Daniel ;

Ataro, Zerihun ;

Atout, Maha Moh'd Wahbi ;

Ayanore, Martin Amogre ;

Badawi, Alaa ;

Bakhtiari, Ahad ;

Ballew, Shoshana H. ;

Balouchi, Abbas ;

Banach, Maciej ;

Barquera, Simon ;

Basu, Sanjay ;

Bayih, Mulat Tirfie ;

Bedi, Neeraj ;

Bello, Aminu K. ;

Bensenor, Isabela M. ;

Bijani, Ali ;

Boloor, Archith ;

Borzi, Antonio M. ;

Camera, Luis Alberto ;

Carrero, Juan J. ;

Carvalho, Felix ;

Castro, Franz ;

Catala-Lopez, Ferran ;

Chang, Alex R. ;

Chin, Ken Lee ;

Chung, Sheng-Chia ;

Cirillo, Massimo .

LANCET, 2020, 395 (10225) :709-733

[2]

Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy [J].

Brenner, BM ;

Cooper, ME ;

de Zeeuw, D ;

Keane, WF ;

Mitch, WE ;

Parving, HH ;

Remuzzi, G ;

Snapinn, SM ;

Zhang, ZX ;

Shahinfar, S .

NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (12) :861-869

[3]

Quantity and Reporting Quality of Kidney Research [J].

Chatzimanouil, Markos Kyriakos Tomidis ;

Wilkens, Louise ;

Anders, Hans-Joachim .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2019, 30 (01) :13-22

[4]

Cherney DZI, 2020, LANCET DIABETES ENDO, V8, P582, DOI 10.1016/S2213-8587(20)30162-5

[5]

Fatal refractory cardiac arrest as presentation of systemic amyloidosis [J].

Chung, Peter ;

Wheeler, Sarah ;

Fong, Andrew ;

Hurth, Kyle ;

Yaghmour, Bassam .

RESPIRATORY MEDICINE CASE REPORTS, 2020, 30

[6]

Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial [J].

Heerspink, Hiddo J. L. ;

Stefansson, Bergur, V ;

Chertow, Glenn M. ;

Correa-Rotter, Ricardo ;

Greene, Tom ;

Hou, Fan-Fan ;

Lindberg, Magnus ;

McMurray, John ;

Rossing, Peter ;

Toto, Roberto ;

Langkilde, Anna Maria ;

Wheeler, David C. .

NEPHROLOGY DIALYSIS TRANSPLANTATION, 2020, 35 (02) :274-282

[7]

Renoprotective effects of sodium-glucose cotransporter-2 inhibitors [J].

Heerspink, Hiddo J. L. ;

Kosiborod, Mikhail ;

Inzucchi, Silvio E. ;

Cherney, David Z. I. .

KIDNEY INTERNATIONAL, 2018, 94 (01) :26-39

[8]

Efficacy and safety of benazepril for advanced chronic renal insufficiency [J].

Hou, FF ;

Zhang, X ;

Zhang, GH ;

Xie, D ;

Chen, PY ;

Zhang, WR ;

Jiang, JP ;

Liang, M ;

Wang, GB ;

Liu, ZR ;

Geng, RW .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (02) :131-140

[9]

Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes [J].

Lewis, EJ ;

Hunsicker, LG ;

Clarke, WR ;

Berl, T ;

Pohl, MA ;

Lewis, JB ;

Ritz, E ;

Atkins, RC ;

Rohde, R ;

Raz, I .

NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (12) :851-860

[10]

Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction [J].

McMurray, J. J. V. ;

Solomon, S. D. ;

Inzucchi, S. E. ;

Kober, L. ;

Kosiborod, M. N. ;

Martinez, F. A. ;

Ponikowski, P. ;

Sabatine, M. S. ;

Anand, I. S. ;

Belohlavek, J. ;

Bohm, M. ;

Chiang, C. -E. ;

Chopra, V. K. ;

de Boer, R. A. ;

Desai, A. S. ;

Diez, M. ;

Drozdz, J. ;

Dukat, A. ;

Ge, J. ;

Howlett, J. G. ;

Katova, T. ;

Kitakaze, M. ;

Ljungman, C. E. A. ;

Merkely, B. ;

Nicolau, J. C. ;

O'Meara, E. ;

Petrie, M. C. ;

Vinh, P. N. ;

Schou, M. ;

Tereshchenko, S. ;

Verma, S. ;

Held, C. ;

DeMets, D. L. ;

Docherty, K. F. ;

Jhund, P. S. ;

Bengtsson, O. ;

Sjostrand, M. ;

Langkilde, A. -M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2019, 381 (21) :1995-2008

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