The long-term effects of dapagliflozin in chronic kidney disease: a time-to-event analysis.
A time-to-event modeling analysis of DAPA-CKD trial data projected that dapagliflozin delays the mean time to kidney failure by approximately 6.6 years in the DAPA-CKD population, with similar long-term cardiorenal benefits in a broader pooled CKD population.
Background
Chronic kidney disease imposes a major clinical and economic burden that rises sharply with progression toward kidney failure. The DAPA-CKD trial showed that dapagliflozin slowed CKD progression versus placebo in patients with and without type 2 diabetes, but the long-term effect on the timing of kidney failure beyond trial follow-up was not directly observed.
Study design
Patient-level data from DAPA-CKD were used to parameterize a closed cohort-level partitioned survival model predicting time-to-event for kidney failure, all-cause mortality, sustained decline in kidney function, and heart failure hospitalization. Data were also pooled with a subpopulation of DECLARE-TIMI 58 to create a combined CKD population spanning a range of CKD stages for a parallel survival analysis.
Key findings
In both the DAPA-CKD and pooled CKD populations, dapagliflozin delayed the time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and heart failure hospitalization. The attenuation of CKD progression was predicted to slow time to kidney failure by 6.6 years in the DAPA-CKD population (dapagliflozin 25.2 vs standard therapy 18.5 years) and by 6.3 years in the pooled CKD population.
Clinical implications
Long-term treatment with dapagliflozin may considerably delay the mean time to adverse clinical outcomes, including kidney failure, for CKD patients who would otherwise experience them. These extrapolated projections can help inform shared decision-making between providers and patients about the durable benefits of treatment.
Category
Research
Source
Nephrol Dial Transplant
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