Key result
Empagliflozin slows eGFR decline by ~0.9 mL/min/1.73 m² per year vs. placebo.
Why the study?
The temporal relationship between kidney function changes, heart failure-related events, and the effects of empagliflozin has not been well characterized.
Does empagliflozin modify the longitudinal changes in eGFR before and after heart failure-related events in patients with heart failure?
Meta-Analysis (n=9,554)
Does empagliflozin modify the longitudinal changes in eGFR before and after heart failure-related events in patients with heart failure?
Kidney function decline accelerates around the time of heart failure events, and empagliflozin attenuates this eGFR decline regardless of event occurrence.
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“In EMPEROR-Pooled, kidney function decline accelerated during the year preceding an HF event across the LVEF spectrum and remained rapid for 1 year thereafter. Empagliflozin attenuated eGFR decline in patients without an HF event and before HF events, whereas the difference after an HF event was smaller and not statistically significant.”
Empagliflozin attenuates accelerated eGFR decline around HF events; extends kidney-protection evidence across the HF trajectory.
BACKGROUND: Kidney function decline in heart failure (HF) may accelerate during periods surrounding HF-related events, while sodium-glucose cotransporter 2 inhibitors slow kidney function decline. However, the temporal relationship between kidney function changes, HF-related events, and treatment effects has not been well characterized. AIMS: We aimed to explore kidney function trajectories around HF-related events and to assess whether empagliflozin modifies these changes. METHODS AND RESULTS: In a pooled analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials, we examined longitudinal changes in estimated glomerular filtration rate (eGFR) before and after HF-related events, defined as HF hospitalization or HF-related death. In the EMPEROR-Pooled analysis, HF-related events occurred in 12.7% of 9554 patients during a median follow-up of 20.9 months (14.7-28.6). Patients who experienced HF-related events had a steeper eGFR decline during the 12 months before the event than those without HF-related events: average -5.01 ml/min/1.73 m2/year vs -1.93 ml/min/1.73 m2/year; P < .001. During the 12 months after HF-related events, eGFR decline persisted at an average rate of -4.73 ml/min/1.73 m2/year. These trajectories were not materially altered after adjustment for concurrent NYHA class or natriuretic peptide levels. Compared with placebo, empagliflozin slowed eGFR decline in patients without events (between-group difference, 0.94 ml/min/1.73 m2/year) and before events (1.09 ml/min/1.73 m2/year). The post-event difference was smaller (0.29 ml/min/1.73 m2/year), without significant heterogeneity across periods (P > .10). Findings were consistent across trials and irrespective of prior HF hospitalization. CONCLUSION: Across the LVEF spectrum, kidney function decline accelerated before HF-related events and remained rapid thereafter. Empagliflozin attenuated eGFR decline without evidence of heterogeneity across periods.
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Kobayashi et al. (2026) conducted a meta-analysis in Heart failure (n=9,554). Empagliflozin vs. Placebo was evaluated on Change in eGFR in patients without heart failure-related events (Between-group difference 0.94). Empagliflozin attenuated eGFR decline compared to placebo in patients without HF events (difference 0.94 ml/min/1.73 m2/year) and before events (1.09 ml/min/1.73 m2/year).
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