Efficacy and Safety of Dapagliflozin in Patients With CKD Across Major Geographic Regions

Priya Vart, Ricardo Correa-Rotter, Fan Fan Hou, Niels Jongs, Glenn M Chertow, Anna Maria Langkilde, John J V McMurray, Peter Rossing, C David Sjöström, Bergur V Stefansson, Robert D Toto, Walter Douthat, Elizabeth Escudero, Rey Isidto, Dinesh Khullar, Harpreet S Bajaj, David C Wheeler, Hiddo J L Heerspink, Priya Vart, Ricardo Correa-Rotter, Fan Fan Hou, Niels Jongs, Glenn M Chertow, Anna Maria Langkilde, John J V McMurray, Peter Rossing, C David Sjöström, Bergur V Stefansson, Robert D Toto, Walter Douthat, Elizabeth Escudero, Rey Isidto, Dinesh Khullar, Harpreet S Bajaj, David C Wheeler, Hiddo J L Heerspink

Abstract

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.

Keywords: SGLT-2 inhibitor; dapagliflozin; efficacy; regions; safety.

© 2022 International Society of Nephrology. Published by Elsevier Inc.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Cumulative incidence of primary end point by major geographic region. (a) Asia; (b) Europe; (c) Latin America; and (d) North America.
Figure 2
Figure 2
Efficacy of dapagliflozin for primary and key secondary end points by major geographic region. eGFR, estimated glomerular filtration rate.

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Source: PubMed

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