Kidney Function After Initiation And Discontinuation Of Empagliflozin (EMPA) In Heart Failure (HF) Patients (Pts) With And Without Type 2 Diabetes (T2D): Insights From The Emperial Trials

Introduction EMPA induces an initial decline in estimated glomerular filtration rate (eGFR) in T2D pts. Although considered hemodynamic and reversible, it may raise concerns in clinical practice. This phenomenon needs to be better understood in pts with HF, beyond T2D. Hypothesis To assess eGFR after starting/stopping EMPA in HF pts with/without T2D in the EMPERIAL (Effect of EMPagliflozin on ExeRcise ability and heart failure symptoms In patients with chronic heArt faiLure)-Reduced and -Preserved trials. Methods Pts with HF (NYHA class II-IV, diagnosed ≥3 months prior), baseline eGFR >20 mL/min/1.73 m2, elevated NT-proBNP, and LVEF ≤40% in EMPERIAL-Reduced and >40% in -Preserved, received placebo (PBO) or EMPA 10mg. Overall and across subgroups by baseline T2D status, eGFR changes were analyzed for pooled EMPA (both EMPERIAL trials) vs PBO using a mixed model repeated measures analysis. Acute renal failure (ARF) incidence was assessed by investigator-reported adverse events (AEs) coded according to the narrow standardized MedDRA query. Results EMPERIAL-Reduced and -Preserved included 312 (156 EMPA, 156 PBO) and 315 pts (157 EMPA, 158 PBO), respectively. At baseline in the pooled data set, 55.6% had T2D. Overall, mean baseline eGFR±SD was 57.6±19.3 mL/min/1.73 m2. PBO-adjusted mean eGFR±SE change from baseline with pooled EMPA was -2.3±0.7 and -3.3±0.8 at Weeks 6 and 12, respectively (Figure A). Change in eGFR±SE from last value on treatment to follow-up was -0.3±0.5 in PBO and +3.9±0.5 in EMPA groups (Figure A). These findings were consistent across subgroups by baseline T2D status (Figure B). Incidence rates of ARF were similar in PBO and EMPA groups (n=9 and n=8; 11.8 and 10.7 per 100pt-years, respectively), and also consistent across subgroups by baseline T2D status. Serious ARF occurred in 4 PBO pts and 1 EMPA pt. Conclusions In HF pts with baseline eGFR down to 20 mL/min/1.73 m2, eGFR dynamics after starting/stopping EMPA and kidney AEs were similar to EMPA's known eGFR change on and off treatment, and kidney safety profile, regardless of T2D status.