The EMPEROR-Reduced (NCT03057977) and EMPEROR-Preserved (NCT03057951) trials demonstrated that empagliflozin could reduce the risk of hospitalization for heart failure (HF) both in patients with HF and reduced left ventricular ejection fraction (LVEF) and patients with HF and preserved LVEF. However, the effect of empagliflozin on renal function is unknown.
Investigators planned a prospective pooled analysis of results from the EMPEROR-Reduced and EMPEROR-Preserved trials, to compare major adverse renal events experienced by participants receiving empagliflozin1. A total of 9718 patients across the two trials were randomized to receive either empagliflozin (n=4860) or a placebo (n=4858). The primary outcome of the pooled analysis was a composite of major adverse renal outcomes, defined as a decrease in estimated glomerular filtration rate (eGFR) or the need for renal replacement therapy.
After a median follow-up period of 21 months, 138 (2.8%) of patients in the empagliflozin group, and 170 (3.5%) of patients in the placebo group had experienced a major adverse renal event. In the EMPEROR-Reduced trial, the hazard ratio (HR) for serious renal outcomes was 0.51 (95% confidence interval [CI] 0.33-0.79), while in the EMPEROR-Preserved trial, the HR was 0.95 (95% CI 0.73-1.24).
Researchers noted that ejection fraction plays a role in renal outcomes experienced with the use of empagliflozin; major adverse renal events were reduced in the EMPEROR-Reduced trial, while in the EMPEROR-Preserved trial, they were not. The adjusted mean difference in annualized decline in eGFR in the EMPEROR-Reduced trial was nearly double that in the EMPEROR-Preserved trial (HR 1.77, 95% CI 0.80-2.74 vs. HR 0.94, 95% CI 0.60-1.27 mL/minute per 1.73m2).
This finding contrasts with the observation that the rate of decline of eGFR was slower in patients taking empagliflozin than in patients taking placebo in the EMPEROR-Preserved trial, as reported by Anker et. al2. Packer et al. concluded that eGFR slope analysis may not be a valid surrogate marker to predict the renal effect of drugs used in patients with HF.
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Author: Kelly Schoonderwoerd