The long-term effects of dapagliflozin in chronic kidney disease: a time-to-event analysis.

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. 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. 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). 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. © The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.

Citation

Phil McEwan, Peter D Gabb, Jason A Davis, Juan Jose Garcia Sanchez, C David Sjöström, Salvatore Barone, Pavlos Kashioulis, Mario Ouwens, Syd Cassimaty, Ricardo Correa-Rotter, Peter Rossing, David C Wheeler, Hiddo J L Heerspink. The long-term effects of dapagliflozin in chronic kidney disease: a time-to-event analysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2024 Nov 27;39(12):2040-2047

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PMID: 38730538

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