Vart, Priya;
Butt, Jawad H;
Jongs, Niels;
Schechter, Meir;
Chertow, Glenn M;
Wheeler, David C;
Pecoits-Filho, Roberto;
... Heerspink, Hiddo JL; + view all
(2023)
Efficacy and Safety of Dapagliflozin in Patients with Chronic Kidney Disease across the Spectrum of Frailty.
The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences
, Article glad181. 10.1093/gerona/glad181.
(In press).
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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 estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m 2 and urinary albumin-to-creatinine ratio 200-5000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was 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 4303/4304 (99.9%) patients: 1162 (27.0%) in not-to-mildly frail(FI≤0.210), 1642 (38.2%) in moderately frail(FI 0.211-0.310), and 1499 (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% 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=0.42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin vs. 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.
| Type: | Article |
|---|---|
| Title: | Efficacy and Safety of Dapagliflozin in Patients with Chronic Kidney Disease across the Spectrum of Frailty |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/gerona/glad181 |
| Publisher version: | https://doi.org/10.1093/gerona/glad181 |
| Language: | English |
| Additional information: | © The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. This is an Open Access article distributed under the terms of the Creative Commons AttributionNonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits noncommercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| Keywords: | SGLT2 inhibitors, cardiovascular disease, diabetes |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10175383 |
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