Eur J Heart Fail. 2023 Apr 16. doi: 10.1002/ejhf.2857. Online ahead of print.
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 .