TY - JOUR

T1 - Empagliflozin in heart failure patients with reduced ejection fraction

T2 - a randomized clinical trial (Empire HF)

AU - Jensen, Jesper

AU - Omar, Massar

AU - Kistorp, Caroline

AU - Poulsen, Mikael Kjær

AU - Tuxen, Christian

AU - Gustafsson, Ida

AU - Køber, Lars

AU - Gustafsson, Finn

AU - Fosbøl, Emil

AU - Bruun, Niels Eske

AU - Videbæk, Lars

AU - Frederiksen, Peter Hartmund

AU - Møller, Jacob Eifer

AU - Schou, Morten

PY - 2019

Y1 - 2019

N2 - 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.TRIAL REGISTRATION: Clinicaltrialsregister.eu, EudraCT Number 2017-001341-27 . Registered on 29 May 2017. ClinicalTrials.gov, NCT03198585 . Registered on 26 June 2017.

AB - 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.TRIAL REGISTRATION: Clinicaltrialsregister.eu, EudraCT Number 2017-001341-27 . Registered on 29 May 2017. ClinicalTrials.gov, NCT03198585 . Registered on 26 June 2017.

KW - Benzhydryl Compounds/adverse effects

KW - Diabetes Mellitus, Type 2/complications

KW - Double-Blind Method

KW - Glucosides/adverse effects

KW - Heart Failure/drug therapy

KW - Humans

KW - Natriuretic Peptide, Brain/blood

KW - Peptide Fragments/blood

KW - Quality of Life

KW - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use

KW - Stroke Volume/drug effects

U2 - 10.1186/s13063-019-3474-5

DO - 10.1186/s13063-019-3474-5

M3 - Journal article

C2 - 31227014

VL - 20

JO - Trials

JF - Trials

SN - 1745-6215

M1 - 374

ER -