Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Aug;25(8):1337-1348.
doi: 10.1002/ejhf.2857. Epub 2023 May 4.

Cardiac and kidney benefits of empagliflozin in heart failure across the spectrum of kidney function: Insights from the EMPEROR-Preserved trial

Abhinav Sharma  1 , João Pedro Ferreira  2   3 , Faiez Zannad  3 , Stuart J Pocock  4 , Gerasimos Filippatos  5 , Egon Pfarr  6 , Michaela Petrini  7 , Bettina J Kraus  8 , Christoph Wanner  9 , Milton Packer  10   11 , Javed Butler  12   13 , Stefan D Anker  14   15   16   17
Affiliations
Free article
Randomized Controlled Trial

Cardiac and kidney benefits of empagliflozin in heart failure across the spectrum of kidney function: Insights from the EMPEROR-Preserved trial

Abhinav Sharma et al. Eur J Heart Fail. 2023 Aug.
Free article

Abstract

Aim: In the EMPEROR-Preserved trial, empagliflozin improved clinical outcomes of patients with heart failure (HF) with preserved ejection fraction. In this pre-specified analysis, we aim to study the effect of empagliflozin on cardiovascular and kidney outcomes across the spectrum of kidney function.

Methods and results: Patients were categorized by the presence or absence of chronic kidney disease (CKD) at baseline (CKD defined by an estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 or urine albumin to creatinine ratio >300 mg/g). The primary and key secondary outcomes were (i) a composite of cardiovascular death or first HF hospitalization (primary outcome); (ii) total number of HF hospitalization, (iii) eGFR slope; and a pre-specified exploratory composite kidney outcome including a sustained ≥40% decline in eGFR, chronic dialysis or renal transplant. The median follow-up was 26.2 months. A total of 5988 patients were randomized to empagliflozin or placebo, of whom 3198 (53.5%) had CKD. Irrespective of CKD status, empagliflozin reduced the primary outcome (with CKD: hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69-0.94; without CKD: HR 0.75, 95% CI 0.60-0.95; interaction p = 0.67) and total (first and recurrent) hospitalizations for HF (with CKD: HR 0.68, 95% CI 0.54-0.86; without CKD: HR 0.89, 95% CI 0.66-1.21; interaction p = 0.17). Empagliflozin slowed the slope of eGFR decline by 1.43 (1.01-1.85) ml/min/1.73 m2 /year in patients with CKD and 1.31 (0.88-1.74) ml/min/1.73 m2 /year in patients without CKD (interaction p = 0.70). Empagliflozin did not reduce the pre-specified kidney outcome in patients with or without CKD (with CKD: HR 0.97, 95% CI 0.71-1.34; without CKD: HR 0.92, 95% CI 0.58-1.48; interaction p = 0.86) but slowed progression to macroalbuminuria and reduced the risk of acute kidney injury. The effect of empagliflozin on the primary composite outcome and the key secondary outcomes was consistent across five baseline eGFR categories (all interaction p >0.05). Empagliflozin was well tolerated independent of CKD status.

Conclusions: In EMPEROR-Preserved, empagliflozin had a beneficial effect on the key efficacy outcomes in patients with and without CKD. Overall, the benefit and safety of empagliflozin was consistent across a wide range of kidney function spectrum, down to a baseline eGFR of 20 ml/min/1.73 m2 .

Keywords: Chronic disease; Empagliflozin; Glomerular filtration rate; Heart failure; Renal insufficiency.

PubMed Disclaimer

Comment in

References

    1. Sharma A, Butler J, Zieroth S, Giannetti N, Verma S. Treatment of heart failure with sodium glucose co-transporter-2 inhibitors in people with type 2 diabetes mellitus: current evidence and future directions. Diabet Med. 2019;36:1550-61.
    1. Neuen BL, Young T, Heerspink HJL, Neal B, Perkovic V, Billot L, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7:845-54.
    1. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al.; EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323-34.
    1. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al.; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-28.
    1. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al.; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644-57.

Publication types

MeSH terms