In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.
Did you know that your browser is out of date? To get the best experience using our website we recommend that you upgrade to a newer version. Learn more.

Empagliflozin benefits heart failure patients with reduced and preserved ejection fraction

EMPEROR-Pooled analysis presented in a Hot Line Session today at ESC Congress 2021

Heart Failure

Sophia Antipolis, France – 27 Aug 2021:  A pooled analysis of two randomised trials has demonstrated the beneficial effects of empagliflozin in patients with heart failure with a reduced and preserved ejection fraction. The late breaking study is presented in a Hot Line session today at ESC Congress 20211 and published in the New England Journal of Medicine.2

The EMPEROR-Reduced trial previously showed that the sodium–glucose co-transporter 2 (SGLT2) inhibitor empagliflozin reduced the risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure and a reduced ejection fraction.3 Results of the EMPEROR-Preserved trial, presented at ESC Congress 2021, demonstrated that the drug also reduced this composite cardiovascular endpoint in patients with heart failure and a preserved ejection fraction.

The current analysis pooled the results of these two trials on an individual patient level. This was possible because of the similarities between both studies. The trials were carried out in parallel with nearly identical protocols, case report forms, investigative sites, and administrative committees. Both trials evaluated the effects of empagliflozin versus placebo in a randomised and double-blind fashion in patients with established heart failure receiving all appropriate treatments. Empagliflozin or placebo was given for an average of 24 months. The major difference was the enrolment of patients with heart failure and an ejection fraction of 40% or less in EMPEROR-Reduced and patients with heart failure and an ejection fraction of more than 40% in EMPEROR-Preserved.

Principal investigator Dr. Milton Packer of Baylor University Medical Center, Dallas, US said: “This analysis was prospectively designed and we developed a statistical plan before any patient was recruited in either trial. The evaluation was alpha-protected, meaning that the endpoints were statistically powerful and unbiased because by specifying the pooled analysis in the individual trials it was protected from an inflated false positive error rate.”

A total of 9,718 patients were included in the analysis. The evaluation demonstrated that empagliflozin reduced the risk of heart failure hospitalisation to a similar degree (about 30% risk reduction) in EMPEROR-Preserved and in EMPEROR-Reduced.

The magnitude of the effect on heart failure hospitalisations was similar across a broad range of ejection fractions below 65%, with attenuation of the drug effect at higher ejection fractions (65% or greater). At ejection fractions of 40–60%, the effect size appeared to be greater with empagliflozin than in the PARAGON-HF trial where sacubitril/valsartan was compared to valsartan.4

The analysis also found that empagliflozin reduced the risk of major renal outcomes in EMPEROR-Reduced, but not in EMPEROR-Preserved. However, in EMPEROR-Preserved, when renal outcomes were defined using more stringent criteria, pretreatment ejection fraction influenced the effect of empagliflozin on renal outcomes in a manner that paralleled the drug’s effect on heart failure hospitalisations.

Dr. Packer said: “Taken together, these findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure with a reduced and preserved ejection fraction, including many not effectively treated with currently available agents.”


Notes to editor

ESC Press Office
Tel: +33 (0) 7 8531 2036

Follow us on Twitter @ESCardioNews 

The hashtag for ESC Congress 2021 is #ESCCongress.

This press release accompanies both a presentation and an ESC press conference at ESC Congress 2021. It does not necessarily reflect the opinion of the European Society of Cardiology.

Funding: Boehringer Ingelheim and Eli Lilly and Company funded EMPEROR-Reduced and EMPEROR-Preserved.

Disclosures: MP was the Chair of the Executive Committee for the EMPEROR Trials Programme and has served and continued to serve as a consultant to Boehringer Ingelheim in matters related to the EMPEROR-Reduced and EMPEROR-Preserved trials. MP is a consultant to Eli Lilly & Company on matters unrelated to the EMPEROR Programme.

References and notes

1EMPEROR-Pooled: effect of empagliflozin on serious adverse renal outcomes in chronic heart failure – a prospective alpha-protected, Individual patient-level pooled analysis.

2Anker S et al. Empagliflozin in Heart Failure With a Preserved Ejection Fraction (EMPEROR-Preserved). N Engl J Med. 10.1056/NEJMoa2107038

3Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413–1424.

4Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin–neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381:1609–1620.

About the European Society of Cardiology

The ESC brings together health care professionals from more than 150 countries, working to advance cardiovascular medicine and help people to live longer, healthier lives.

About ESC Congress 2021 - The Digital Experience

It is the world’s largest gathering of cardiovascular professionals, disseminating ground-breaking science in a new digital format. Online each day – from 27 to 30 August. Explore the scientific programme. More information is available from the ESC Press Office at