Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis

McEwan, P. et al. (2022) Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis. Nephrology Dialysis Transplantation, (doi: 10.1093/ndt/gfac280) (PMID:36301617) (Early Online Publication)

Abstract

Background: The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial assessed dapagliflozin versus placebo, in addition to standard therapy, in patients with chronic kidney disease (CKD) and albuminuria, and was terminated prematurely due to overwhelming efficacy. The study objective was to model the long-term clinical outcomes of DAPA-CKD beyond the trial follow-up. Methods: A Markov model extrapolated event incidence per 1000 patients and CKD progression rates for patients receiving dapagliflozin or placebo over a 10-year time horizon. We derived treatment-specific CKD stage transition matrices using DAPA-CKD trial data. We extrapolated relevant efficacy endpoints using parametric survival equations for all-cause mortality and generalized estimating equations for recurrent events. Results: When extrapolated over a 10-year period, patients randomized to dapagliflozin spent more time in CKD stages 1–3 and less in stages 4–5 than placebo [0.65 (95% CrI 0.41, 0.90) and –0.23 (95% CrI -0.45, 0.00) years per patient, respectively]. Dapagliflozin prevented an estimated 83 deaths and 51 patients initiating kidney replacement therapy per 1000 patients over 10 years. Predicted rates of hospitalized heart failure and abrupt declines in kidney function were reduced (19 and 39 estimated events per 1000 patients, respectively). Conclusions: Adding dapagliflozin to standard therapeutic management of CKD is expected to have long-term cardiorenal benefit beyond what has been demonstrated in the DAPA-CKD trial, with patients predicted to live longer with fewer complications.

• Item Type: Articles
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: McEwan, P., Boyce, R., Sanchez, J. J. G., Sjöström, C. D., Stefansson, B., Nolan, S., Correa-Rotter, R., Rossing, P., Chertow, G. M., McMurray, J. J.V., Wheeler, D. C., and Heerspink, H. J. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Nephrology Dialysis Transplantation
• Publisher: Oxford University Press
• ISSN: 0931-0509
• ISSN (Online): 1460-2385
• Published Online: 06 October 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Nephrology Dialysis Transplantation 2022
• Publisher Policy: Reproduced under a Creative Commons License