Evaluation of the effect of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial.
Diabetes
Heart failure
Reduced ejection fraction
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:
20
05
2019
accepted:
23
05
2019
pubmed:
5
10
2019
medline:
6
10
2020
entrez:
5
10
2019
Statut:
ppublish
Résumé
Drugs that inhibit the sodium-glucose co-transporter 2 (SGLT2) have been shown to reduce the risk of hospitalizations for heart failure in patients with type 2 diabetes. In populations that largely did not have heart failure at the time of enrolment, empagliflozin, canagliflozin and dapagliflozin decreased the risk of serious new-onset heart failure events by ≈30%. In addition, in the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of both pump failure and sudden deaths, the two most common modes of death among patients with heart failure. In none of the three trials could the benefits of SGLT2 inhibitors on heart failure be explained by the actions of these drugs as diuretics or anti-hyperglycaemic agents. These observations raise the possibility that SGLT2 inhibitors could reduce morbidity and mortality in patients with established heart failure, including those without diabetes. The EMPEROR-Reduced trial is enrolling ≈3600 patients with heart failure and a reduced left ventricular ejection fraction (≤ 40%), half of whom are expected not to have diabetes. Patients are being randomized to placebo or empagliflozin 10 mg daily, which is added to all appropriate treatment with inhibitors of the renin-angiotensin system and neprilysin, beta-blockers and mineralocorticoid receptor antagonists. The primary endpoint is the time-to-first event analysis of the combined risk of cardiovascular death and hospitalization for heart failure, but the trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality, and recurrent hospitalization events. By adjusting eligibility based on natriuretic peptide levels to the baseline ejection fraction, the trial will preferentially enrol high-risk patients. A large proportion of the participants is expected to have an ejection fraction < 30%, and the estimated annual event rate is expected to be at least 15%. The EMPEROR-Reduced trial is well-positioned to determine if the addition of empagliflozin can add meaningfully to current approaches that have established benefits in the treatment of chronic heart failure with left ventricular systolic dysfunction.
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
1270-1278Investigateurs
Milton Packer
(M)
Stefan D Anker
(SD)
Javed Butler
(J)
Gerasimos Filippatos
(G)
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)
Jindrich Spinar
(J)
Marie-France Seronde
(MF)
Michael Böhm
(M)
Bela Merkely
(B)
Vijay Chopra
(V)
Michele Senni
(M)
Stefano Taddei
(S)
Hiroyuki Tsutsui
(H)
Dong-Ju Choi
(DJ)
Eduardo Chuquiure
(E)
Hans Pieter Brunner La Rocca
(HPB)
Piotr Ponikowski
(P)
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)
Informations de copyright
© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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