TY - JOUR
T1 - Extrapolated longer-term effects of the DAPA-CKD trial
T2 - a modelling analysis
AU - McEwan, Phil
AU - Boyce, Rebecca
AU - Sanchez, Juan Jose Garcia
AU - Sjöström, C David
AU - Stefansson, Bergur
AU - Nolan, Stephen
AU - Correa-Rotter, Ricardo
AU - Rossing, Peter
AU - Chertow, Glenn M
AU - McMurray, John J V
AU - Wheeler, David C
AU - Heerspink, Hiddo J L
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - 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.
AB - 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.
KW - Benzhydryl Compounds/therapeutic use
KW - Diabetes Mellitus, Type 2/complications
KW - Heart Failure/complications
KW - Humans
KW - Renal Insufficiency, Chronic/complications
KW - Sodium-Glucose Transporter 2 Inhibitors/adverse effects
KW - dialysis
KW - chronic kidney disease
KW - dapagliflozin
KW - kidney transplantation
KW - SGLT2 inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85159547398&partnerID=8YFLogxK
U2 - 10.1093/ndt/gfac280
DO - 10.1093/ndt/gfac280
M3 - Journal article
C2 - 36301617
SN - 0931-0509
VL - 38
SP - 1260
EP - 1270
JO - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
IS - 5
ER -