In the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin decreased cardiovascular (CV) death or heart failure (HF) hospitalization, total HF hospitalizations, and reduced the progressive decline in kidney function in patients with HF and a reduced ejection fraction (HFrEF), with and without diabetes.

In a recent publication in Circulation, Zannad et al explored the effect of empagliflozin on CV and renal outcomes across the spectrum of kidney function. In this prespecified analysis, patients were categorized by the presence or absence of chronic kidney disease (CKD) at baseline (eGFR <60 mL/min/1.73m2 or UACR >300 mg/g).

The primary and key secondary outcomes were a composite of CV death or HF hospitalization (primary outcome); total HF hospitalizations; and estimated glomerular filtration rate (eGFR slope). The direct impact on kidney events was examined by a prespecified composite kidney outcome (defined as a sustained profound decline in eGFR, chronic dialysis, or transplant). The average follow-up was 16 months.

Zannad et al reported that 3,730 patients were randomized to empagliflozin or placebo, of whom 1,978 (53%) had CKD. Empagliflozin diminished the primary outcome and total HF hospitalizations in patients with and without CKD: primary outcome HR = 0.78 (95% CI, 0.65-0.93) and HR = 0.72 (95% CI, 0.58-0.90), respectively; interaction P = .63. Empagliflozin slowed the slope of eGFR decline by 1.11 (0.23-1.98) mL/min/1.73m2/year in patients with CKD and by 2.41 (1.49-3.32) mL/min/1.73m2/year in patients without CKD.

The risk of the composite kidney outcome was diminished comparably in patients with and without CKD: HR = 0.53 (95% CI, 0.31-0.91) and HR = 0.46 (95% CI, 0.22-0.99), respectively. The effect of empagliflozin on the primary composite outcome and the key secondary outcomes was consistent across a wide range of baseline kidney functions, measured by clinically relevant eGFR subgroups or by albuminuria, including patients with eGFR as low as 20 mL/min/1.73m2.

Empagliflozin was well tolerated in CKD patients. The researchers concluded that in the EMPEROR-Reduced trial, empagliflozin had a favorable effect on the main efficacy outcomes and decelerated the rate of kidney function decline in patients with and without CKD, regardless of the severity of kidney impairment at baseline.

In a recent presentation, Dr. Zannad, MD, PhD, EMPEROR Program clinical investigator and emeritus professor of Therapeutics at the University of Lorraine, France, stated, “In EMPEROR-Reduced, empagliflozin demonstrated a consistent reduction in the risk of the composite primary endpoint of cardiovascular death and heart failure hospitalizations, while slowing kidney function decline, in adults with heart failure with reduced ejection fraction, with and without chronic kidney disease. This is promising news for the growing population of adults suffering from both heart failure and chronic kidney disease.”
 
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