Early Changes in Estimated Glomerular Filtration Rate Post-initiation of Empagliflozin in EMPEROR-Reduced Heart Failure Trial

Diabetologie und Stoffwechsel, vol. 17, pp. S66

Abstract

Aims Sodium glucose co-transporter-2 inhibitors may induce an early post-initiation decrease in eGFR without impacting their benefits in patients with diabetes. The effects of initial eGFR change in heart failure (HF) are not yet described. We investigated eGFR change and its impact in EMPEROR-Reduced trial participants with HF with reduced ejection fraction, who were treated with empagliflozin 10 mg/day or placebo. Methods Landmark Week 4 analyses were performed to assess the risk of outcomes across tertiles (T1–T3) of percent eGFR change from randomisation in empagliflozin- and placebo-treated participants, using Cox regression models with adjustment for percent eGFR change and baseline factors considered prognostic. The primary outcome was cardiovascular mortality/HF hospitalisation; other key outcomes were cardiovascular mortality, sustained worsening kidney function, and all-cause mortality. Results Among 3547 participants (95%) with available data, empagliflozin versus placebo induced a leftward distributional shift in mean eGFR of -2.5 ml/min/1.73m 2 at Week 4. With placebo, risk for sustained worsening kidney function was higher in the tertile with largest decrease (T1; eGFR change ≤ -6.5%) versus the tertile with largest increase (T3; ≥ 3.6%): HR (95% CI) 2.38 (1.25–4.55). With empagliflozin, risk for all assessed outcomes was not increased in T1 (≤-11.4%) versus T3 (≥0.0%); HR (95% CI) for the primary endpoint: 0.86 (0.66–1.11). Conclusions In EMPEROR-Reduced, modest post-treatment-initiation eGFR decrease was more frequent with empagliflozin than placebo. Only with placebo, eGFR decrease was associated with higher sustained worsening kidney function risk. Any post-empagliflozin-initiation decrease in eGFR did not deprive participants of empagliflozin treatment benefits. Publication History Article published online: 26 May 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Authors 1

1. Nikolaus Marx corresponding Aachen Department of Internal Medicine I (Cardiology)

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   University Hospital Aachen, RWTH Aachen University, Department of Internal Medicine I, Aachen, Germany