Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial
| Autor: | David C. Wheeler, Tom Greene, John J.V. McMurray, Hiddo J.L. Heerspink, Robert D. Toto, Anna Maria Langkilde, Glenn M. Chertow, Bergur V. Stefánsson, Fan Fan Hou, Ricardo Correa-Rotter, Dapa-Ckd Trial Committees, Investigators, Peter Rossing, C. David Sjöström, Niels Jongs |
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| Přispěvatelé: | Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Kidney Center (GKC) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Endocrinology Diabetes and Metabolism Benzhydryl Compounds/adverse effects Type 2 diabetes Kidney/drug effects Kidney Kidney Failure Diabetic nephropathy chemistry.chemical_compound 0302 clinical medicine Endocrinology Glucosides Kidney Failure Chronic/chemically induced Diabetic Nephropathies Renal Insufficiency 030212 general & internal medicine Dapagliflozin Middle Aged Cardiovascular Diseases/chemically induced Type 2/complications Treatment Outcome Cardiovascular Diseases Female Adult Chronic/complications medicine.medical_specialty Renal Insufficiency Chronic/complications Renal function 030209 endocrinology & metabolism Glucosides/adverse effects 03 medical and health sciences Chronic/chemically induced Double-Blind Method Diabetes mellitus Internal medicine Diabetes Mellitus Internal Medicine medicine Humans Benzhydryl Compounds Renal Insufficiency Chronic Adverse effect Heart Failure/chemically induced Aged Heart Failure business.industry Diabetes Mellitus Type 2/complications medicine.disease Diabetes Mellitus Type 2 chemistry Heart failure Diabetic Nephropathies/drug therapy Kidney Failure Chronic business Kidney disease |
| Zdroj: | Lancet Diabetes & Endocrinology, 9(1), 22-31. ELSEVIER SCIENCE INC DAPA-CKD Trial Committees and Investigators 2021, ' Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease : a prespecified analysis from the DAPA-CKD trial ', The Lancet Diabetes and Endocrinology, vol. 9, no. 1, pp. 22-31 . https://doi.org/10.1016/S2213-8587(20)30369-7 |
| ISSN: | 2213-8587 |
| DOI: | 10.1016/S2213-8587(20)30369-7 |
| Popis: | Background: Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause. Methods: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200–5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25–75 mL/min per 1·73m2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150. Findings: The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0–2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52–0·79) and those without diabetes (0·50, 0·35–0·72; pinteraction=0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45–0·73] vs 0·51 [0·34–0·75]; Pinteraction=0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53–0·92] vs 0·79 [0·40–1·55]; Pinteraction=0·78), and all-cause mortality (0·74 [0·56–0·98] vs 0·52 [0·29–0·93]; Pinteraction=0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51–0·78), glomerulonephritides (n=695; 0·43, 0·26–0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44–1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29–1·19; Pinteraction=0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes. Interpretation: Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease. Funding: AstraZeneca. |
| Databáze: | OpenAIRE |
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