Decline in Estimated Glomerular Filtration Rate After Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Secondary Analysis of the DELIVER Randomized Clinical Trial

JAMA Cardiol. 2023; online ahead of print DOI: 10.1001/jamacardio.2023.4664

An initial decline in eGFR often occurs after initiating a SGLT2i and has been observed in patients with diabetes, CKD and HF. A prespecified analysis of DELIVER evaluated the magnitude and frequency of an initial decline in eGFR (within the first month) and its association with CV and renal outcomes in 5,788 patients with HFpEF or HFmrEF.

A higher proportion of patients assigned to dapagliflozin developed an initial eGFR decline >10% vs placebo (40% vs 25%; odds ratio, 1.9; 95% CI 1.7–2.1; P<0.001). An initial eGFR decline >10% (vs ≤10%) was associated with a higher risk of the primary cardiovascular outcome (CV death or HF event) in the placebo group (adjusted hazard ratio 1.33; 95% CI 1.10–1.62) but not the dapagliflozin group (0.90; 95% CI 0.74–1.09; P for interaction = 0.01). An initial eGFR decline >10% was not associated with adverse subsequent kidney composite outcomes (≥50% eGFR decline, eGFR <15 or dialysis, death from kidney causes) in dapagliflozin-treated patients (0.94; 95% CI 0.49–1.82).

These data suggest that SGLT2i should not be discontinued in response to an initial eGFR decline in patients with HFmrEF or HFpEF.