Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis
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Extrapolated longer-term effects of the DAPA-CKD trial : a modelling analysis. / McEwan, Phil; Boyce, Rebecca; Sanchez, Juan Jose Garcia; Sjöström, C. David; Stefansson, Bergur; Nolan, Stephen; Correa-Rotter, Ricardo; Rossing, Peter; Chertow, Glenn M.; McMurray, John J. V.; Wheeler, David C.; Heerspink, Hiddo J. L.
I: Nephrology Dialysis Transplantation, Bind 38, Nr. 5, 2023, s. 1260-1270.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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.
PY - 2023
Y1 - 2023
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 - chronic kidney disease
KW - dapagliflozin
KW - dialysis
KW - kidney transplantation
KW - SGLT2 inhibitor
KW - CHRONIC KIDNEY-DISEASE
KW - POST-HOC ANALYSIS
KW - ADVERSE OUTCOMES
KW - DAPAGLIFLOZIN
KW - CANAGLIFLOZIN
KW - HYPERTENSION
KW - PROGRESSION
KW - PREVENTION
U2 - 10.1093/ndt/gfac280
DO - 10.1093/ndt/gfac280
M3 - Journal article
C2 - 36301617
VL - 38
SP - 1260
EP - 1270
JO - Nephrology, Dialysis, Transplantation
JF - Nephrology, Dialysis, Transplantation
SN - 0931-0509
IS - 5
ER -
ID: 345424443