Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial.
Diabetes
Heart failure
SGLT2 inhibitors
Trial design
Journal
European journal of heart failure
ISSN: 1879-0844
Titre abrégé: Eur J Heart Fail
Pays: England
ID NLM: 100887595
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
17
04
2019
revised:
27
07
2019
accepted:
30
07
2019
pubmed:
17
9
2019
medline:
6
10
2020
entrez:
17
9
2019
Statut:
ppublish
Résumé
The principal biological processes that characterize heart failure with a preserved ejection fraction (HFpEF) are systemic inflammation, epicardial adipose tissue accumulation, coronary microcirculatory rarefaction, myocardial fibrosis and vascular stiffness; the resulting impairment of left ventricular and aortic distensibility (especially when accompanied by impaired glomerular function and sodium retention) causes increases in cardiac filling pressures and exertional dyspnoea despite the relative preservation of left ventricular ejection fraction. Independently of their actions on blood glucose, sodium-glucose co-transporter 2 (SGLT2) inhibitors exert a broad range of biological effects (including actions to inhibit cardiac inflammation and fibrosis, antagonize sodium retention and improve glomerular function) that can ameliorate the pathophysiological derangements in HFpEF. Such SGLT2 inhibitors exert favourable effects in experimental models of HFpEF and have been found in large-scale trials to reduce the risk for serious heart failure events in patients with type 2 diabetes, many of whom were retrospectively identified as having HFpEF. The EMPEROR-Preserved Trial is enrolling ≈5750 patients with HFpEF (ejection fraction >40%), with and without type 2 diabetes, who are randomized to receive placebo or empagliflozin 10 mg/day, which is added to all appropriate treatments for HFpEF and co-morbidities. The primary endpoint is the time-to-first-event analysis of the combined risk for cardiovascular death or hospitalization for heart failure. The trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality and recurrent hospitalization events, and will assess a wide range of biomarkers that reflect important pathophysiological mechanisms that may drive the evolution of HFpEF. The EMPEROR-Preserved Trial is well positioned to determine if empagliflozin can have a meaningful impact on the course of HFpEF, a disorder for which there are currently few therapeutic options.
Sections du résumé
BACKGROUND
The principal biological processes that characterize heart failure with a preserved ejection fraction (HFpEF) are systemic inflammation, epicardial adipose tissue accumulation, coronary microcirculatory rarefaction, myocardial fibrosis and vascular stiffness; the resulting impairment of left ventricular and aortic distensibility (especially when accompanied by impaired glomerular function and sodium retention) causes increases in cardiac filling pressures and exertional dyspnoea despite the relative preservation of left ventricular ejection fraction. Independently of their actions on blood glucose, sodium-glucose co-transporter 2 (SGLT2) inhibitors exert a broad range of biological effects (including actions to inhibit cardiac inflammation and fibrosis, antagonize sodium retention and improve glomerular function) that can ameliorate the pathophysiological derangements in HFpEF. Such SGLT2 inhibitors exert favourable effects in experimental models of HFpEF and have been found in large-scale trials to reduce the risk for serious heart failure events in patients with type 2 diabetes, many of whom were retrospectively identified as having HFpEF.
STUDY DESIGN
The EMPEROR-Preserved Trial is enrolling ≈5750 patients with HFpEF (ejection fraction >40%), with and without type 2 diabetes, who are randomized to receive placebo or empagliflozin 10 mg/day, which is added to all appropriate treatments for HFpEF and co-morbidities.
STUDY AIMS
The primary endpoint is the time-to-first-event analysis of the combined risk for cardiovascular death or hospitalization for heart failure. The trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality and recurrent hospitalization events, and will assess a wide range of biomarkers that reflect important pathophysiological mechanisms that may drive the evolution of HFpEF. The EMPEROR-Preserved Trial is well positioned to determine if empagliflozin can have a meaningful impact on the course of HFpEF, a disorder for which there are currently few therapeutic options.
Substances chimiques
Benzhydryl Compounds
0
Glucosides
0
Sodium-Glucose Transporter 2 Inhibitors
0
empagliflozin
HDC1R2M35U
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1279-1287Investigateurs
Milton Packer
(M)
Stefan D Anker
(SD)
Javed Butler
(J)
Gerasimos S Filippatos
(GS)
Faiez Zannad
(F)
Jyothis George
(J)
Martina Brueckmann
(M)
Sergio Perrone
(S)
Stephen Nicholls
(S)
Stefan Janssens
(S)
Edmar Bocchi
(E)
Nadia Giannetti
(N)
Subodh Verma
(S)
Zhang Jian
(Z)
Juan Esteban Gomez Mesa
(JE)
Jindrich Spinar
(J)
Michael Böhm
(M)
Bela Merkely
(B)
Vijay Chopra
(V)
Michele Senni
(M)
Stefano Taddi
(S)
Hiroyuki Tsutsui
(H)
Eduardo Chuquiure
(E)
Hans Pieter Brunner La Rocca
(HPB)
Piotr Ponikowski
(P)
Dragos Vinereanu
(D)
David Sim
(D)
Dong-Ju Choi
(DJ)
Jose Ramon Gonzalez Juanatey
(JRG)
Iain Squire
(I)
Javed Butler
(J)
James Januzzi
(J)
Ileana Pina
(I)
Stuart J Pocock
(SJ)
Peter Carson
(P)
Wolfram Doehner
(W)
Alan Miller
(A)
Markus Haas
(M)
Steen Pehrson
(S)
Michel Komajda
(M)
Inder Anand
(I)
John Teerlink
(J)
Alejandro Rabinstein
(A)
Thorsten Steiner
(T)
Hooman Kamel
(H)
Georgios Tsivgoulis
(G)
James Lewis
(J)
James Freston
(J)
Neil Kaplowitz
(N)
Johannes Mann
(J)
Mark Petrie
(M)
Richard Bernstein
(R)
Alfred Cheung
(A)
Jennifer Green
(J)
James Januzzi
(J)
Sanjay Kaul
(S)
Carolyn Lam Su Ping
(CLS)
Gregory Lip
(G)
Nikolaus Marx
(N)
Peter McCullough
(P)
Cyrus Mehta
(C)
Piotr Ponikowski
(P)
Julio Rosenstock
(J)
Naveed Sattar
(N)
Benjamin Scirica
(B)
Hiroyuki Tsutsui
(H)
Subodh Verma
(S)
Christoph Wanner
(C)
Francine K Welty
(FK)
Klaus G Parhofer
(KG)
Tim Clayton
(T)
Terje R Pedersen
(TR)
Kennedy R Lees
(KR)
Marvin A Konstam
(MA)
Barry Greenberg
(B)
Mike Palmer
(M)
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.
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