Abstract
BACKGROUND: The DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular medication use modified the dapagliflozin treatment effect. METHODS AND RESULTS: We randomized 4304 adults with baseline estimated glomerular filtration rate 25 to 75 mL/min per 1.73 m2 and urinary albumin:creatinine ratio 200 to 5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary end point was a composite of ≥50% estimated glomerular filtration rate decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. We categorized patients according to baseline cardiovascular medication use/nonuse. Patients were required by protocol to receive a stable (and maximally tolerated) dose of a renin-angiotensin-aldosterone system inhibitor. We observed consistent benefits of dapagliflozin relative to placebo, irrespective of baseline use/nonuse of renin-angiotensin-aldosterone system inhibitors (98.1%), calcium channel blockers (50.7%), β-adrenergic antagonists (39.0%), diuretics (43.7%), and an-tithrombotic (47.4%), and lipid-lowering (15.0%) agents. Use of these drugs in combination with dapagliflozin did not increase the number of serious adverse events. CONCLUSIONS: The safety profile and efficacy of dapagliflozin on kidney and cardiovascular end points in patients with chronic kidney disease were consistent among patients treated and not treated at baseline with a range of cardiovascular medications.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e028739 |
| Tidsskrift | Journal of the American Heart Association |
| Vol/bind | 12 |
| Udgave nummer | 9 |
| Antal sider | 22 |
| ISSN | 2047-9980 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:Dr Chertow has received fees from AstraZeneca for service on the DAPA-CKD trial steering committee. He serves on the Board of Directors for Satellite Healthcare. He has served on other trial steering committees for Akebia, AstraZeneca, Gilead, Sanifit, and Vertex, and on data safety monitoring boards for Bayer, Mineralys, and ReCor. He has served as an advisor and received fees and/or stock options from Ardelyx, CloudCath, Durect, Miromatrix, Outset, and Unicycive. He has received research grants from the National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, Lung, and Blood Institute, and National Institute of Allergy and Infectious Diseases. Dr Correa-Rotter has received fees from AbbVie, AstraZeneca, GlaxoSmithKline, Medtronic, and Boehringer Ingelheim, and has lectured for Amgen, Janssen, Takeda, AstraZeneca, and Boehringer Ingelheim and has received research support from GlaxoSmithKline, Novo Nordisk, and AstraZeneca. P. Vart reports receiving a travel grant from AstraZeneca. Dr McMurray has received payments to his employer, Glasgow University, for his work on clinical trials, consulting, and other activities from AstraZeneca, Cytokinetics, KBP Biosciences, Amgen, Bayer, Theracos, Ionis Pharmaceuticals, Dalcor Pharmaceuticals, Novartis, GlaxoSmithKline, Bristol Myers Squibb, Boehringer Ingelheim, Cardurion, and Alnylam, and has received personal lecture fees from Abbott, Alkem Metabolics, Eris Life Sciences, Hickma, Lupin, Sun Pharmaceuticals, Medscape/Heart.org, ProAdWise Communications, Radcliffe Cardiology, Servier, and the Corpus. Dr Rossing has received fees to Steno Diabetes Center Copenhagen for: steering group membership and/or lectures and advice from AstraZeneca, Novo Nordisk, Bayer, and Eli Lilly; advisory board participation from Sanofi Aventis and Boehringer Ingelheim; and steering group participation from Gilead. Dr Langkilde and Dr Sjöström are employees and stockholders of AstraZeneca. Dr Toto is a member of the Executive Committee of the DAPA-CKD study, has received consulting fees from Boehringer Ingelheim, Reata Pharma, and Chinook, and payment from Medscape and Medical Education Resources, participated in advisory boards for Bayer and Vioforand on data monitoring committees for Akebia and Otsuka.
Funding Information:
The authors thank all patients, investigators, and research teams for their time spent on the DAPA-CKD trial. Editorial support was provided by Lise Magnollay and Nicola Truss, inScience Communications, Springer Healthcare Ltd, London, UK, and funded by AstraZeneca.
Publisher Copyright:
© 2023 The Authors and AstraZeneca. Published on behalf of the American Heart Association, Inc., by Wiley.