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Randomized Controlled Trial
. 2023 May 4;38(5):1260-1270.
doi: 10.1093/ndt/gfac280.

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

Phil McEwan  1 , Rebecca Boyce  1 , Juan Jose Garcia Sanchez  2 , C David Sjöström  3 , Bergur Stefansson  3 , Stephen Nolan  4 , Ricardo Correa-Rotter  5 , Peter Rossing  6   7 , Glenn M Chertow  8 , John J V McMurray  9 , David C Wheeler  10 , Hiddo J L Heerspink  11   12
Affiliations
Randomized Controlled Trial

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

Phil McEwan et al. Nephrol Dial Transplant. .

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.

Keywords: SGLT2 inhibitor; chronic kidney disease; dapagliflozin; dialysis; kidney transplantation.

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Conflict of interest statement

P.M. and R.B. are/were employees of Health Economics and Outcomes Research Ltd, Cardiff, UK. Health Economics and Outcomes Research Ltd received fees from AstraZeneca in relation to this study. J.J.G.S., C.D.S., B.S. and S.N. are employees of AstraZeneca. R.C.-R. has received honoraria as consultant from: AstraZeneca, Boehringer Ingelheim, Janssen, Bayer, Chinook, AbbVie and Novo Nordisk, and research support from AstraZeneca, GSK and Novo Nordisk. P.R. has received honoraria to Steno Diabetes Center Copenhagen for consultancy from AstraZeneca, Astellas, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi and Vifor, and research support from AstraZeneca and Novo Nordisk. G.M.C. has received honoraria as consultant from: Akebia, Amgen, Ardelyx, AstraZeneca, Baxter, Cricket, DiaMedica, Gilead, Miromatrix, Outset, Reata, Sanifit and Vertex. He has received research support from Amgen and Janssen. He has served on data and safety monitoring boards for Angion, Bayer and Recor. J.J.V.M. reports non-financial support and other from AstraZeneca, during the conduct of the study; non-financial support and other from Cardiorentis, Amgen, Oxford University/Bayer, Theracos, AbbVie, other from DalCor, Pfizer, Novartis, GSK, Vifor-Fresenius, Kidney Research UK, Bayer, Merck and Bristol-Myers Squibb, outside the submitted work. D.C.W. provides ongoing consultancy services to AstraZeneca and has received honoraria and/or consultancy fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, GSK, Janssen, Napp, Mundipharma, Medscape, Merck Sharp and Dohme, Pharmacosmos, Reata, Takeda and Vifor-Fresenius. H.J.L.H. is a consultant for AstraZeneca, AbbVie, Boehringer Ingelheim, CSL Behring, Bayer, Chinook, Dimerix, Gilead, Goldfinch, Merck, Novo Nordisk, Janssen and Travere Pharmaceuticals. He received research support from AstraZeneca, Boehringer Ingelheim, Janssen and Novo Nordisk.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
Model schematic.
Figure 2:
Figure 2:
Cumulative incidence of ACM, HHF and abrupt decline in kidney function and (top to bottom) per 1000 patients treated with placebo versus dapagliflozin, in addition to standard therapy, over a 10-year horizon. ST: standard therapy.
Figure 3:
Figure 3:
Cumulative incidence of ACM per 1000 patients treated with placebo versus dapagliflozin, in addition to standard therapy, over a 10-year horizon.
Figure 4:
Figure 4:
Cumulative incidence of KRT initiation per 1000 patients treated with placebo versus dapagliflozin, in addition to standard therapy, over a 10-year horizon.
Figure 5:
Figure 5:
Cumulative incidence of HHF per 1000 patients treated with placebo versus dapagliflozin, in addition to standard therapy, over a 10-year horizon.
Figure 6:
Figure 6:
Cumulative incidence of abrupt declines in kidney function per 1000 patients treated with placebo versus dapagliflozin, in addition to standard therapy, over a 10-year horizon.
See this image and copyright information in PMC

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