In patients with heart failure and a lower ejection fraction, sodium-glucose cotransporter 2 inhibitors have been shown to prevent heart failure episodes and delay the course of renal disease. The purpose of the Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial was to assess the impact of dapagliflozin on cardiovascular and kidney outcomes and the influence of baseline kidney disease in patients with heart failure and a mildly reduced or preserved ejection fraction. The DELIVER randomized clinical study was analyzed according to predefined criteria from July 1, 2022, through September 18, 2022. Patients having an ejection fraction of 40% or higher and an estimated glomerular filtration rate (eGFR) of 25 mL/min/1.73 m2 or above participated in this global, multicenter study.

The impact of therapy on the main outcome was evaluated, and its significance was adjusted for differences in kidney function at baseline (cardiovascular death or worsening heart failure). Also analyzed was the treatment’s impact on the prespecified endpoint of eGFR slope, as well as a post hoc composite renal outcome (first ≥50% drop in eGFR from baseline; first eGFR <15 mL/min/1.73 m2; end-stage kidney disease; death from kidney causes). Mean (SD) eGFR values were 61 (19) mL/min/1.73 m2 for 6,262 patients (mean [SD] age, 72 [10] years; 3,516 male [56%]), while 3,070 patients (49%) had an eGFR of less than 60 mL/min/1.73 m2. Dapagliflozin’s impact on the main outcome was similar across eGFR categories at baseline (eGFR ≥60 mL/min/1.73 m2: hazard ratio [HR], 0.84; 95% CI, 0.70-1.00; eGFR 45-<60 mL/min/1.73 m2: HR, 0.68; 95% CI, 0.54-0.87; eGFR <45 mL/min/1.73 m2: HR, 0.93; 95% CI, 0.76-1.14; P= .16). 

The incidence rate of the renal composite outcome was modest (1.1 occurrences per 100 patient-years) and was not influenced by therapy with dapagliflozin (HR, 1.08; 95% CI, 0.79-1.49), with a median (IQR) follow-up of 2.3 (1.7-2.8) years. Dapagliflozin, on the other hand, slowed the rate of reduction in eGFR both from baseline (difference, 0.5; 95% CI, 0.1-0.9 mL/min/1.73 m2 per year; P=.01) and from month 1 to 36 (difference, 1.4; 95% CI, 1.0-1.8) mL/min/1.73 m2 per year; P< .001). The prespecified study demonstrated that the benefit of dapagliflozin in individuals with heart failure and modestly decreased or maintained ejection fraction was not affected by renal function at baseline. Although the total event rate was modest, dapagliflozin did not substantially lower the frequency of the renal composite outcome. The reduction in eGFR was reduced by dapagliflozin compared to placebo.