Efficacy and safety of dapagliflozin in patients with chronic kidney disease across the spectrum of frailty

Vart, P. et al. (2024) Efficacy and safety of dapagliflozin in patients with chronic kidney disease across the spectrum of frailty. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 79(2), glad181. (doi: 10.1093/gerona/glad181) (PMID:37527836) (PMCID:PMC10809037)

Abstract

Background: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level. Methods: Adults with CKD, with/without type 2 diabetes, with an estimated glomerular filtration rate (eGFR) of 25–75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200–5 000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), or death from kidney or cardiovascular (CV) causes. Results: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4 303/4 304 (99.9%) patients: 1 162 (27.0%) in not-to-mildly frail (FI ≤0.210), 1 642 (38.2%) in moderately frail (FI 0.211–0.310), and 1 499 (34.8%) in severely frail categories (FI >0.311). Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% confidence interval {CI}]: 0.50 [0.33–0.76], 0.62 [0.45–0.85], and 0.64 [0.49–-0.83], respectively; p-interaction = 0.67). Results were similar for secondary outcomes including kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; p-interaction = 0.44), CV endpoint (heart failure hospitalization or CV death; p-interaction = 0.63), and all-cause mortality (p-interaction p = .42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin versus placebo in all FI categories (16.9% vs 20.1%, 26.3% vs 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately, and severely frail categories, respectively). Conclusions: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associated safety.

• Item Type: Articles
• Additional Information: This study was funded by AstraZeneca.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Butt, Mr Jawad and McMurray, Professor John
• Authors: Vart, P., Butt, J. H., Jongs, N., Schechter, M., Chertow, G. M., Wheeler, D. C., Pecoits-Filho, R., Langkilde, A. M., Correa-Rotter, R., Rossing, P., McMurray, J. J. V., and Heerspink, H. J. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journals of Gerontology Series A: Biological Sciences and Medical Sciences
• Publisher: Oxford University Press
• ISSN: 1079-5006
• ISSN (Online): 1758-535X
• Published Online: 01 August 2023
• Copyright Holders: Copyright © 2023 The Author(s)
• First Published: First published in Journals of Gerontology Series A: Biological Sciences and Medical Sciences 79(2):glad181
• Publisher Policy: Reproduced under a Creative Commons license