Abstract | AIMS/HYPOTHESIS: METHODS: DAPA-CKD was a double-blind, placebo-controlled trial that randomised patients with an eGFR of 25-75 ml min-1 [1.73 m]-2 and urinary albumin/ creatinine ratio (UACR) of ≥22.6 and <565.0 mg/mmol (200-5000 mg/g) to dapagliflozin 10 mg/day or placebo. The primary endpoint was a composite of ≥50% reduction in eGFR, end-stage kidney disease (ESKD), and death from a kidney or cardiovascular cause. Secondary endpoints included a kidney composite (≥50% reduction in eGFR, ESKD and death from a kidney cause), a cardiovascular composite ( heart failure hospitalisation or cardiovascular death), and death from all causes. We used Cox proportional hazards regression analyses to assess relative and absolute effects of dapagliflozin across KDIGO risk categories. RESULTS: Of the 4304 participants in the DAPA-CKD study, 619 (14.4%) were moderately high risk, 1349 (31.3%) were high risk and 2336 (54.3%) were very high risk when categorised by KDIGO risk categories at baseline. Dapagliflozin reduced the hazard of the primary composite (HR 0.61; 95% CI 0.51, 0.72) and secondary endpoints consistently across KDIGO risk categories (all p for interaction >0.09). Absolute risk reductions for the primary outcome were also consistent irrespective of KDIGO risk category (p for interaction 0.26). Analysing patients with and without type 2 diabetes separately, the relative risk reduction with dapagliflozin in terms of the primary outcome was consistent across subgroups of KDIGO risk categories. The relative frequencies of adverse events and serious adverse events were also similar across KDIGO risk categories. CONCLUSION/INTERPRETATIONS: The consistent benefits of dapagliflozin on kidney and cardiovascular outcomes across KDIGO risk categories indicate that dapagliflozin is efficacious and safe across a wide spectrum of kidney disease severity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03036150. FUNDING: The study was funded by AstraZeneca.
|
Authors | Simke W Waijer, Priya Vart, David Z I Cherney, Glenn M Chertow, Niels Jongs, Anna Maria Langkilde, Johannes F E Mann, Ofri Mosenzon, John J V McMurray, Peter Rossing, Ricardo Correa-Rotter, Bergur V Stefansson, Robert D Toto, David C Wheeler, Hiddo J L Heerspink |
Journal | Diabetologia
(Diabetologia)
Vol. 65
Issue 7
Pg. 1085-1097
(07 2022)
ISSN: 1432-0428 [Electronic] Germany |
PMID | 35445820
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Copyright | © 2022. The Author(s). |
Chemical References |
- Benzhydryl Compounds
- Glucosides
- Sodium-Glucose Transporter 2 Inhibitors
- dapagliflozin
|
Topics |
- Benzhydryl Compounds
(pharmacology)
- Cardiovascular Diseases
(prevention & control)
- Diabetes Mellitus, Type 2
(complications)
- Glomerular Filtration Rate
- Glucosides
- Heart Failure
(complications)
- Humans
- Kidney
- Kidney Failure, Chronic
(complications)
- Renal Insufficiency, Chronic
(drug therapy, etiology)
- Sodium-Glucose Transporter 2 Inhibitors
(pharmacology)
|