Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved
Stefan D Anker
(1, 2)
,
Javed Butler
(3, 4)
,
Muhammad Shariq Usman
(5)
,
Gerasimos Filippatos
(6)
,
João Pedro Ferreira
(7, 8, 9, 10)
,
Edimar Bocchi
(11)
,
Michael Böhm
(12)
,
Hans Pieter Brunner-La Rocca
(13, 14)
,
Dong-Ju Choi
(15)
,
Vijay Chopra
(16)
,
Eduardo Chuquiure
(17)
,
Nadia Giannetti
(18)
,
Juan Esteban Gomez-Mesa
(19)
,
Stefan Janssens
(20)
,
James L Januzzi
(21, 22)
,
José R González-Juanatey
(23)
,
Bela Merkely
(24)
,
Stephen J Nicholls
(25)
,
Sergio V Perrone
(26, 27)
,
Ileana L Piña
(28)
,
Piotr Ponikowski
(1)
,
Michele Senni
(29)
,
David Sim
(30)
,
Jindrich Spinar
(31, 32)
,
Iain Squire
(33)
,
Stefano Taddei
(34)
,
Hiroyuki Tsutsui
(35)
,
Subodh Verma
(36, 37)
,
Dragos Vinereanu
(38, 39)
,
Jian Zhang
(40)
,
Tomoko Iwata
(41)
,
Janet M Schnee
(42)
,
Martina Brueckmann
(42, 43)
,
Stuart J Pocock
(44)
,
Faiez Zannad
(7, 8, 9)
1
Wrocław Medical University
2 Charité - UniversitätsMedizin = Berlin University Medicine
3 Baylor Scott and White Research Institute [Dallas, TX, USA]
4 Mississippi State University [Mississippi]
5 UMMC - University of Mississippi Medical Center
6 University of Athens Medical School [Athens]
7 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]
8 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
9 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
10 Universidade do Porto = University of Porto
11 USP - Universidade de São Paulo = University of São Paulo
12 UKS - Saarland University Hospital
13 CARIM - Cardiovascular Research Institute Maastricht
14 MUMC - Maastricht University Medical Centre
15 SNUBH - Seoul National University Bundang Hospital
16 MSH - MAX Superspecialty Hospital [Saket, New Delhi, India]
17 National Institute of Cardiology, Mexico City
18 MUHC - McGill University Health Center [Montreal]
19 ICESI - Universidad Icesi
20 University Hospitals Leuven [Leuven]
21 Massachusetts General Hospital [Boston]
22 Baim Institute for Clinical Research Boston MA
23 CIBERCV - Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares [Spain]
24 Semmelweis University [Budapest]
25 Monash University [Melbourne]
26 UCA - Pontifical Catholic University of Argentina
27 FLENI - Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires]
28 CMU - Central Michigan University
29 Hosp P Giovanni XXIII - Hospital Papa Giovanni XXIII
30 NHCS - National Heart Centre Singapore
31 MUNI - Masaryk University [Brno]
32 St. Anne’s University Hospital [Brno]
33 University of Leicester
34 UniPi - University of Pisa [Italy] = Università di Pisa [Italia] = Université de Pise [Italie]
35 Kyushu University
36 St. Michael's Hospital
37 University of Toronto
38 SUUB - Spitalul Universitar de Urgență București = University Emergency Hospital [Bucharest, Romania]
39 UMPCD - University of Medicine and Pharmacy “Carol Davila”
40 PUMCH - Peking Union Medical College Hospital [Beijing]
41 Boehringer Ingelheim Pharma GmbH & Co. KG
42 Boehringer Ingelheim International GmbH
43 Universität Heidelberg [Heidelberg] = Heidelberg University
44 LSHTM - London School of Hygiene and Tropical Medicine
2 Charité - UniversitätsMedizin = Berlin University Medicine
3 Baylor Scott and White Research Institute [Dallas, TX, USA]
4 Mississippi State University [Mississippi]
5 UMMC - University of Mississippi Medical Center
6 University of Athens Medical School [Athens]
7 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]
8 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
9 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
10 Universidade do Porto = University of Porto
11 USP - Universidade de São Paulo = University of São Paulo
12 UKS - Saarland University Hospital
13 CARIM - Cardiovascular Research Institute Maastricht
14 MUMC - Maastricht University Medical Centre
15 SNUBH - Seoul National University Bundang Hospital
16 MSH - MAX Superspecialty Hospital [Saket, New Delhi, India]
17 National Institute of Cardiology, Mexico City
18 MUHC - McGill University Health Center [Montreal]
19 ICESI - Universidad Icesi
20 University Hospitals Leuven [Leuven]
21 Massachusetts General Hospital [Boston]
22 Baim Institute for Clinical Research Boston MA
23 CIBERCV - Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares [Spain]
24 Semmelweis University [Budapest]
25 Monash University [Melbourne]
26 UCA - Pontifical Catholic University of Argentina
27 FLENI - Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires]
28 CMU - Central Michigan University
29 Hosp P Giovanni XXIII - Hospital Papa Giovanni XXIII
30 NHCS - National Heart Centre Singapore
31 MUNI - Masaryk University [Brno]
32 St. Anne’s University Hospital [Brno]
33 University of Leicester
34 UniPi - University of Pisa [Italy] = Università di Pisa [Italia] = Université de Pise [Italie]
35 Kyushu University
36 St. Michael's Hospital
37 University of Toronto
38 SUUB - Spitalul Universitar de Urgență București = University Emergency Hospital [Bucharest, Romania]
39 UMPCD - University of Medicine and Pharmacy “Carol Davila”
40 PUMCH - Peking Union Medical College Hospital [Beijing]
41 Boehringer Ingelheim Pharma GmbH & Co. KG
42 Boehringer Ingelheim International GmbH
43 Universität Heidelberg [Heidelberg] = Heidelberg University
44 LSHTM - London School of Hygiene and Tropical Medicine
Stefan D Anker
- Function : Author
- PersonId : 1157761
João Pedro Ferreira
- Function : Author
- PersonId : 800586
- ORCID : 0000-0002-2304-6138
James L Januzzi
- Function : Author
- PersonId : 809149
- ORCID : 0000-0002-8338-1798
Bela Merkely
- Function : Author
- PersonId : 1198619
- ORCID : 0000-0001-6514-0723
Ileana L Piña
- Function : Author
- PersonId : 817603
- ORCID : 0000-0002-4986-7129
Dragos Vinereanu
- Function : Author
- PersonId : 1198620
- ORCID : 0000-0002-9054-8779
Martina Brueckmann
- Function : Author
- PersonId : 795328
- ORCID : 0000-0003-1215-0746
Abstract
The EMPEROR-Preserved trial showed that the sodium–glucose co-transporter 2 inhibitor empagliflozin significantly reduces the risk of cardiovascular death or hospitalization for heart failure (HHF) in heart failure patients with left ventricular ejection fraction (LVEF) > 40%. Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (≥ 50%) ( n = 4,005; 66.9%) or mid-range (41–49%). In patients with LVEF ≥ 50%, empagliflozin reduced the risk of cardiovascular death or HHF (the primary endpoint) by 17% versus placebo (hazard ratio (HR) 0.83; 95% confidence interval (CI): 0.71–0.98, P = 0.024). For the key secondary endpoint, the HR for total HHF was 0.83 (95%CI: 0.66–1.04, P = 0.11). For patients with an LVEF of 41–49%, the HR for empagliflozin versus placebo was 0.71 (95%CI: 0.57–0.88, P = 0.002) for the primary outcome ( P interaction = 0.27), and 0.57 (95%CI: 0.42–0.79, P < 0.001) for total HHF ( P interaction = 0.06). These results, together with those from the EMPEROR-Reduced trial in patients with LVEF < 40%, support the use of empagliflozin across the full spectrum of LVEF in heart failure.
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