TY - JOUR
T1 - Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions
AU - Vart, Priya
AU - Correa-Rotter, Ricardo
AU - Hou, Fan Fan
AU - Jongs, Niels
AU - Chertow, Glenn M.
AU - Langkilde, Anna Maria
AU - McMurray, John J.V.
AU - Rossing, Peter
AU - Sjöström, C. David
AU - Stefansson, Bergur V.
AU - Toto, Robert D.
AU - Douthat, Walter
AU - Escudero, Elizabeth
AU - Isidto, Rey
AU - Khullar, Dinesh
AU - Bajaj, Harpreet S.
AU - Wheeler, David C.
AU - Heerspink, Hiddo J.L.
N1 - Funding Information:
RCR is a member of the Executive Committee of the DAPA-CKD study and has received grants/contracts from GlaxoSmithKline and Novo Nordisk, consulting fees from Boehringer Ingelheim and Chinook, and payment/honoraria as a speaker or advisor from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and Novo Nordisk. FFH is a member of the DAPA-CKD study executive committee and is a study investigator. She has received personal fees from AbbVie. GMC has received fees from AstraZeneca for the DAPA-CKD trial steering committee, research grants from NIDDK, and support for research staff attending meetings from Amgen; participated in data safety monitoring boards for Bayer and Recor; is on the board of directors for Satellite Healthcare and on trial steering committees for Akebia, Gilead, Sanifit, and Vertez; and holds stock options or stock options with Ardelyx, CloudCath, Durect, DxNow, Miromatrix, Outset, and Unicycive. AML, CDS, and BVS are employees and stockholders of AstraZeneca. JJVM has received payments to his employer, Glasgow University, for his work on clinical trials, consulting, and other activities from AstraZeneca, Cytokinetics, KBP Biosciences, Amgen, Bayer, Theracos, Ionis Pharmaceuticals, Dalcor Pharmaceuticals, Novartis, GlaxoSmithKline, Bristol Myers Squibb, Boehringer Ingelheim, Cardurion, and Alnylam, and has received personal lecture fees from Abbott, Alkem Metabolics, Eris Life Sciences, Hickma, Lupin, Sun Pharmaceuticals, Medscape/Heart.org, ProAdWise Communications, Radcliffe Cardiology, Servier, and the Corpus. PR has received honoraria to Steno Diabetes Center Copenhagen for steering group membership and/or lectures and advice from AstraZeneca, Novo Nordisk, Bayer, and Eli Lilly; advisory board participation from Sanofi Aventis and Boehringer Ingelheim; and steering group participation from Gilead. RDT received funding from AstraZeneca for participating in the steering committee for DAPA-CKD. He has received fees for consultancy from Boehringer Ingelheim, Reata Pharma, and Chinook Pharma. He has received honoraria for lectures from Medscape and Medical Education Resources. He has participated in DSMB or advisory boards for Bayer, Viofor, Akebia, and Otsuka. HSB has received honoraria for lectures from Eli Lilly, Novo Nordisk, and Medscape and received support for congress attendance from Novo Nordisk and AstraZeneca. DCW provides ongoing consultancy services to AstraZeneca and received personal fees from Bayer, Boehringer Ingelheim, Astellas, GlaxoSmithKline, Janssen, Napp, Mundipharma, Reata, Vifor Fresenius, and Tricida. HJLH has received funding/honoraria and consulting fees to his institution for Steering Committee membership and/or advisory board participation from AstraZeneca (DAPA-CKD study), AbbVie, Travere Pharmaceuticals, Janssen, Gilead, Bayer, Chinook, Merck, and CSL Pharma; consulting fees from Boehringer Ingelheim and Novo Nordisk; and honoraria for lectures from AstraZeneca; and has participated in advisory boards for Mitsubishi Tanabe and Mundipharma. All the other authors declared no competing interests.
Publisher Copyright:
© 2022 International Society of Nephrology
PY - 2022/4
Y1 - 2022/4
N2 - Introduction: This study aimed to examine the efficacy and safety of dapagliflozin in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (NCT03036150) by geographic region. Methods: Adults with chronic kidney disease (CKD) with or without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25 to 75 ml/min per 1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200 to 5000 mg/g were randomized to dapagliflozin (10 mg once daily) or placebo. The primary end point was a composite of a sustained decline in eGFR of ≥50%, end-stage kidney disease or death from kidney or cardiovascular causes. We categorized recruiting countries into 4 broad global regions: Asia, Europe, Latin America, and North America. Of 4304 randomized patients, 1346 (31.3%) were from Asia, 1233 (28.6%) from Europe, 912 (21.2%) from Latin America, and 813 (18.9%) from North America. Results: The relative risk of the primary composite end point was lower in patients randomized to dapagliflozin (relative to placebo) in all regions, with hazard ratios (95% CI) of 0.70 (0.48–1.00), 0.60 (0.43–0.85), 0.61 (0.43–0.86), and 0.51 (0.34–0.76) among patients from Asia, Europe, Latin America, and North America, respectively. There was no effect modification by region (interaction P = 0.77). Occurrence of serious adverse events (SAEs) was lower among patients randomized to dapagliflozin versus placebo (21.9% vs. 26.8%, 34.1% vs. 38.6%, 29.8% vs. 31.5%, and 34.9% vs. 41.0% in Asia, Europe, Latin America, and North America, respectively). Conclusion: Dapagliflozin reduced kidney and cardiovascular events and prolonged survival in patients with CKD, with and without type 2 diabetes, with no apparent effect modification by geographic region.
AB - Introduction: This study aimed to examine the efficacy and safety of dapagliflozin in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (NCT03036150) by geographic region. Methods: Adults with chronic kidney disease (CKD) with or without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25 to 75 ml/min per 1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200 to 5000 mg/g were randomized to dapagliflozin (10 mg once daily) or placebo. The primary end point was a composite of a sustained decline in eGFR of ≥50%, end-stage kidney disease or death from kidney or cardiovascular causes. We categorized recruiting countries into 4 broad global regions: Asia, Europe, Latin America, and North America. Of 4304 randomized patients, 1346 (31.3%) were from Asia, 1233 (28.6%) from Europe, 912 (21.2%) from Latin America, and 813 (18.9%) from North America. Results: The relative risk of the primary composite end point was lower in patients randomized to dapagliflozin (relative to placebo) in all regions, with hazard ratios (95% CI) of 0.70 (0.48–1.00), 0.60 (0.43–0.85), 0.61 (0.43–0.86), and 0.51 (0.34–0.76) among patients from Asia, Europe, Latin America, and North America, respectively. There was no effect modification by region (interaction P = 0.77). Occurrence of serious adverse events (SAEs) was lower among patients randomized to dapagliflozin versus placebo (21.9% vs. 26.8%, 34.1% vs. 38.6%, 29.8% vs. 31.5%, and 34.9% vs. 41.0% in Asia, Europe, Latin America, and North America, respectively). Conclusion: Dapagliflozin reduced kidney and cardiovascular events and prolonged survival in patients with CKD, with and without type 2 diabetes, with no apparent effect modification by geographic region.
KW - SGLT-2 inhibitor
KW - dapagliflozin
KW - efficacy
KW - regions
KW - safety
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U2 - 10.1016/j.ekir.2022.01.1060
DO - 10.1016/j.ekir.2022.01.1060
M3 - Article
C2 - 35497805
AN - SCOPUS:85125463710
SN - 2468-0249
VL - 7
SP - 699
EP - 707
JO - Kidney International Reports
JF - Kidney International Reports
IS - 4
ER -