Abstract
Introduction: Mineralocorticoid receptor antagonists (MRAs) and sodium–glucose cotransporter-2 (SGLT2) inhibitors reduce the risk of kidney failure in chronic kidney disease (CKD). We performed an analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial by baseline conventional MRA (spironolactone and eplerenone) prescription. Methods: Participants with CKD (estimated glomerular filtration rate [eGFR] 25–75 ml/min per 1.73 m2; urinary albumin-to-creatinine ratio 200–500 mg/g), with or without type 2 diabetes, were randomized 1:1 to dapagliflozin 10 mg or placebo, once daily. The primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or kidney or cardiovascular (CV) death. A prespecified kidney-specific secondary outcome was as the primary outcome but without CV death. Hyperkalemia (serum potassium ≥6.0 mmol/l) was an exploratory end point. Time-to-event analyses (proportional hazards [Cox] regression) assessed dapagliflozin versus placebo in patient subgroups defined by baseline conventional MRA use. Results: A total of 229 of 4304 DAPA-CKD participants (5.3%) were receiving conventional MRAs at baseline (dapagliflozin n = 109, placebo n = 120). The effect of dapagliflozin on the primary outcome was consistent in participants prescribed (hazard ratio [HR] 0.76, 95% CI 0.40–1.47) and not prescribed (HR 0.60, 95% CI 0.50–0.72, P-interaction = 0.59) MRAs. This consistency was maintained for the kidney-specific outcome. The effect of dapagliflozin on hyperkalemia (HR 0.87, 95% CI 0.70–1.09) was consistent among those prescribed (HR 0.94, 95% CI 0.41–2.20) and not prescribed (HR 0.87, 95% CI 0.69–1.10, P-interaction = 0.96) MRAs. Adverse events (AEs) leading to discontinuation and serious AEs were similar between treatment groups, regardless of baseline MRA prescription. Conclusion: Dapagliflozin was similarly safe and efficacious in reducing major adverse kidney outcomes in participants with CKD who were or were not prescribed MRAs at baseline.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Kidney International Reports |
| Vol/bind | 7 |
| Udgave nummer | 3 |
| Sider (fra-til) | 436-443 |
| ISSN | 2468-0249 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:This study was funded by AstraZeneca . The authors thank all patients, investigators, and research teams for their time spent on the DAPA-CKD trial. Editorial support was provided by Nicola Truss and Róisín O’Connor, inScience Communications, Springer Healthcare, London, United Kingdom, and funded by AstraZeneca. This study is registered with clinicaltrials.gov ( NCT03036150 ).
Funding Information:
This study was funded by AstraZeneca. The authors thank all patients, investigators, and research teams for their time spent on the DAPA-CKD trial. Editorial support was provided by Nicola Truss and R?is?n O'Connor, inScience Communications, Springer Healthcare, London, United Kingdom, and funded by AstraZeneca. This study is registered with clinicaltrials.gov (NCT03036150). Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca's data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. HJLH was involved in the study design, conduct of the study, data analysis, and interpretation of the data. HJLH and MP wrote the first draft of the manuscript, and MP was involved in data interpretation. GMC, JJVM, RC-R, PR, RDT, DCW, and HJLH are members of the study's executive committee and were involved in the study design, data collection, and analysis/interpretation of the data. NJ and PV performed the data analyses. BVS, CDS, and AML were involved in the study design, conduct of the study, and interpretation of data. All authors reviewed the manuscript drafts for important intellectual content, provided approval of the final version for submission, and take responsibility for the accuracy and integrity of the data, including ensuring that any questions are appropriately investigated and resolved. HJLH is the guarantor and corresponding author and, as such, accepts full responsibility for the overall content of the work and conduct of the study, had access to the data, and attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
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© 2021 International Society of Nephrology