TY - JOUR
T1 - The long-term effects of dapagliflozin in chronic kidney disease
T2 - a time-to-event analysis
AU - McEwan, Phil
AU - Gabb, Peter D
AU - Davis, Jason A
AU - Sanchez, Juan Jose Garcia
AU - Sjöström, C David
AU - Barone, Salvatore
AU - Kashioulis, Pavlos
AU - Ouwens, Mario
AU - Cassimaty, Syd
AU - Correa-Rotter, Ricardo
AU - Rossing, Peter
AU - Wheeler, David C
AU - Heerspink, Hiddo J L
N1 - © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.
PY - 2024/11/27
Y1 - 2024/11/27
N2 - BACKGROUND: Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial demonstrated that patients with or without type 2 diabetes who were treated with dapagliflozin experienced slower progression of CKD versus those receiving placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data.METHODS: Patient-level data from the DAPA-CKD trial were used to parameterize a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function and hospitalization for heart failure). Data were pooled with a subpopulation of the Dapagliflozin Effect on Cardiovascular Events - Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population.RESULTS: In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function and hospitalization for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years [dapagliflozin: 25.2, 95% confidence interval (CI) 19.0-31.5; standard therapy: 18.5, 95% CI 14.7-23.4] in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95% CI 31.9-38.3; standard therapy: 29.6, 95% CI 25.5-34.7).CONCLUSION: Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.
AB - BACKGROUND: Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial demonstrated that patients with or without type 2 diabetes who were treated with dapagliflozin experienced slower progression of CKD versus those receiving placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data.METHODS: Patient-level data from the DAPA-CKD trial were used to parameterize a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function and hospitalization for heart failure). Data were pooled with a subpopulation of the Dapagliflozin Effect on Cardiovascular Events - Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population.RESULTS: In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function and hospitalization for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years [dapagliflozin: 25.2, 95% confidence interval (CI) 19.0-31.5; standard therapy: 18.5, 95% CI 14.7-23.4] in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95% CI 31.9-38.3; standard therapy: 29.6, 95% CI 25.5-34.7).CONCLUSION: Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.
KW - Aged
KW - Benzhydryl Compounds/therapeutic use
KW - Diabetes Mellitus, Type 2/drug therapy
KW - Disease Progression
KW - Female
KW - Follow-Up Studies
KW - Glomerular Filtration Rate
KW - Glucosides/therapeutic use
KW - Humans
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Renal Insufficiency, Chronic/drug therapy
KW - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
UR - http://www.scopus.com/inward/record.url?scp=85201278105&partnerID=8YFLogxK
U2 - 10.1093/ndt/gfae106
DO - 10.1093/ndt/gfae106
M3 - Journal article
C2 - 38730538
SN - 0931-0509
VL - 39
SP - 2040
EP - 2047
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 - 12
ER -