Key result
Empagliflozin cuts CV death or first HF hospitalization risk ~23% across CKD categories.
Why the study?
Empagliflozin reduces major heart failure outcomes, but its effects across the spectrum of chronic kidney disease risk categories needed evaluation.
Does empagliflozin reduce cardiovascular death and heart failure hospitalizations across different KDIGO chronic kidney disease risk categories in patients with heart failure?
Meta-Analysis (n=9,718)
double-blind, placebo-controlled
stratified by geographic region, diabetes status, eGFR, and LVEF
Yes
Does empagliflozin reduce cardiovascular death and heart failure hospitalizations across different KDIGO chronic kidney disease risk categories in patients with heart failure?
Empagliflozin provides consistent cardiovascular and kidney-protective benefits in heart failure patients across the full spectrum of baseline chronic kidney disease severity.
Empagliflozin benefits heart failure patients across all KDIGO categories; confirms consistent efficacy irrespective of baseline CKD severity.
BACKGROUND: Empagliflozin reduces the risk of major heart failure outcomes in heart failure with reduced or preserved ejection fraction. OBJECTIVES: The goal of this study was to evaluate the effect of empagliflozin across the spectrum of chronic kidney disease in a pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced or Preserved Ejection Fraction, respectively). METHODS: A total of 9,718 patients were grouped into Kidney Disease Improving Global Outcomes (KDIGO) categories based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio into low-, moderate-, high-, and very-high-risk categories, comprising 32.0%, 29.1%, 21.9%, and 17.0% of the participants, respectively. RESULTS: In the placebo arm, when compared with lower risk categories, patients at higher risk experienced a slower rate of decline in eGFR, but a higher risk of a composite kidney event. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: 0.66-1.01 for low-; HR: 0.63; 95% CI: 0.52-0.76 for moderate-; HR: 0.82; 95% CI: 0.68-0.98 for high-; and HR: 0.84; 95% CI: 0.71-1.01 for very-high-risk groups; P trend = 0.30). Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope. When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller. In EMPEROR-Reduced, patients at lowest risk experienced the largest effect of empagliflozin on eGFR slope; this pattern was not observed in EMPEROR-Preserved. CONCLUSIONS: The benefit of empagliflozin on major heart failure events was not influenced by KDIGO categories. The magnitude of the renal effects of the drug depended on the approach used to calculate eGFR slopes.
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Butler et al. (2023) conducted a meta-analysis in Heart failure with reduced or preserved ejection fraction across the spectrum of chronic kidney disease (n=9,718). Empagliflozin vs. Placebo was evaluated on Composite of cardiovascular death or first heart failure hospitalization (HR 0.77, 95% CI 0.70-0.84). Empagliflozin significantly reduced the risk of cardiovascular death or first heart failure hospitalization by 23% (HR 0.77, 95% CI 0.70-0.84) across all KDIGO chronic kidney disease risk categories.
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