Empagliflozin in heart failure patients with reduced ejection fraction: a randomized clinical trial (Empire HF)

Jesper JensenEmail author View ORCID ID profile,
Massar Omar,
Caroline Kistorp,
Mikael Kjær Poulsen,
Christian Tuxen,
Ida Gustafsson,
Lars Køber,
Finn Gustafsson,
Emil Fosbøl,
Niels Eske Bruun,
Lars Videbæk,
Peter Hartmund Frederiksen,
Jacob Eifer Møller and
Morten Schou

Trials201920:374

https://doi.org/10.1186/s13063-019-3474-5

Received: 9 January 2019
Accepted: 27 May 2019
Published: 21 June 2019

Open Peer Review reports

Abstract

Background

Data from recent cardiovascular outcome trials in patients with type 2 diabetes (T2D) suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors can prevent development of heart failure (HF) and prolong life in patients without HF. Ongoing event-driven trials are investigating whether the same effect is present in patients with well-defined HF. The mechanism behind the effect of SGLT2 inhibitors in patients with T2D and the potential effect in patients with overt HF is presently unknown.

Methods

This is a randomized, double-blinded, placebo-controlled, parallel group, clinical trial including HF patients with reduced left ventricular ejection fraction (HFrEF) with an ejection fraction ≤ 40% on optimal therapy recruited from specialized HF clinics in Denmark. The primary aim is to investigate the effect of the SGLT2 inhibitor empagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP). Secondary endpoints include cardiac biomarkers, function and hemodynamics, metabolic and renal parameters, daily activity level, and quality of life. Patients are assigned 1:1 to 90 days treatment with empagliflozin 10 mg daily or placebo. Patients with T2D are required to be on recommended doses of anti-glycemic therapy with a hemoglobin A1c (HbA1c) of 6.5–10.0% (48–86 mmol/mol). To show a between-group difference in the change of NT-proBNP of 30%, a total of 189 patients will be included.

Discussion

The Empire HF trial will elucidate the effects and modes of action of empagliflozin in HFrEF patients with and without T2D and provide important mechanistic data which will complement ongoing event-driven trials.