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 -