LAUSR

BACKGROUND In the EMPEROR-Preserved trial, empagliflozin improved clinical outcomes of patients with heart failure with preserved ejection fraction. In this pre-specified analysis, we aim to study the effect of empagliflozin on cardiovascular and kidney outcomes across the spectrum of kidney function. METHODS Patients were categorized by the presence or absence of chronic kidney disease (CKD) at baseline (CKD defined by an estimated glomerular filtration rate [eGFR] <60ml/min/1.73m2 or urine albumin to creatinine ratio [UACR]>300mg/g). The primary and key secondary outcomes were (1) a composite of cardiovascular death or first HF hospitalization (primary outcome); (2) total number of HF hospitalization, (3) eGFR slope; and a prespecified exploratory composite kidney outcome including a sustained ≥ 40% decline in eGFR, chronic dialysis or renal transplant. The median follow-up was 26.2 months. RESULTS 5,988 patients were randomized to empagliflozin or placebo, of whom 3,198 (53.5%) had CKD. Irrespective of CKD status, empagliflozin reduced the primary outcome (with CKD HR 0.80 [95% CI 0.69, 0.94], and without CKD HR 0.75 [95% CI 0.60 0.95], interaction P=0.67) and total (first and recurrent) hospitalizations for HF (with CKD 0.68, [95% CI 0.54, 0.86], and without CKD 0.89 [95% CI 0.66, 1.21], interaction P=0.17). Empagliflozin slowed the slope of eGFR decline by 1.43 (1.01, 1.85) ml/min/1.73m2 /year in patients with CKD and 1.31 (0.88, 1.74) ml/min/1.73m2 /year without CKD (interaction P=0.70). Empagliflozin did not reduce the pre-specified kidney outcome in patients with or without CKD (with CKD HR 0.97 [95% CI 0.71,1.34]; without CKD HR 0.92 [0.58, 1.48], interaction P=0.86) but slowed progression to macroalbuminuria and reduced the risk of acute kidney injury. The effect of empagliflozin on the primary composite outcome and the key secondary outcomes was consistent across 5 baseline eGFR categories (all interaction p-value > 0.05). Empagliflozin was well tolerated independent of CKD status. CONCLUSIONS In EMPEROR-Preserved, empagliflozin had a beneficial effect on the key efficacy outcomes in patients with and without CKD. Overall, the benefit and safety of empagliflozin was consistent across a wide range of kidney function spectrum, down to a baseline eGFR of 20 ml/min/1.73m2 .