Background: The 3-month period after hospitalization for acute cardiac failure is a vulnerable phase with the highest risk of mortality and rehospitalization. Safety and efficacy of early initiation of sacubitril/valsartan during the index hospitalization for acute decompensated heart failure (ADHF) is unclear. Therefore, we tested whether sacubitril/valsartan could result in a lower rate of a composite outcome of first hospitalization for heart failure and death from cardiovascular causes compared to inhibition of the renin-angiotensin system alone. Methods: We enrolled patients hospitalized for ADHF and reduced ejection fraction at 4 sites; patients were divided into a sacubitril/valsartan group or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) group. All patients were followed up for 3 months after discharge. The primary endpoint was outcomes as a composite of death from cardiovascular causes and rehospitalization for heart failure. Results: In total, 251 patients who received sacubitril/valsartan and 251 patients who received ACEIs/ARBs had similar propensity scores and were included and compared. The primary endpoint was reached in 40 patients (15.9%) treated with sacubitril/valsartan and in 59 patients (23.5%) managed by ACEI/ARB (HR, 0.650; 95% CI: 0.435–0.971; p = 0.035). The NYHA class improved in 72.1% of patients in the sacubitril/valsartan group and in 59.8% of patients in the ACEI/ARB group (HR, 1.303; 95% CI: 1.097–1.548, p = 0.004). The key safety outcomes endpoints did not significantly differ. Conclusions: Among patients hospitalized with ADHF and reduced left ventricular ejection fraction, we observed that sacubitril/valsartan therapy led to reduction in death from cardiovascular causes and rehospitalizations for heart failure when compared to ACEI/ARB therapy alone during the vulnerable phase. Our results support that sacubitril/valsartan may be administered early in the vulnerable phase after ADHF and improves NYHA class.

1.
Ambrosy
AP
,
Fonarow
GC
,
Butler
J
,
Chioncel
O
,
Greene
SJ
,
Vaduganathan
M
, et al.
The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries
.
J Am Coll Cardiol
.
2014
;
63
(
12
):
1123
33
.
2.
Braunwald
E
.
The war against heart failure: the Lancet lecture
.
Lancet
.
2015
;
385
(
9970
):
812
24
.
3.
Kjekshus
J
,
Swedberg
K
,
Snapinn
S
.
Effects of enalapril on long-term mortality in severe congestive heart failure. CONSENSUS trial group
.
Am J Cardiol
.
1992
;
69
(
1
):
103
7
.
4.
CONSENSUS Trial Study Group
.
Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS)
.
N Engl J Med
.
1987
;
316
(
23
):
1429
35
.
5.
Yusuf
S
,
Yusuf
S
,
Pitt
B
,
Davis
CE
,
Hood
WB
,
Cohn
JN
.
Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions
.
N Engl J Med
.
1992
;
327
(
10
):
685
91
.
6.
Garg
R
,
Yusuf
S
.
Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials
.
JAMA
.
1995
;
273
(
18
):
1450
6
.
7.
Packer
M
,
Poole-Wilson
PA
,
Armstrong
PW
,
Cleland
JG
,
Horowitz
JD
,
Massie
BM
, et al.
Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group
.
Circulation
.
1999
;
100
(
23
):
2312
8
.
8.
Yusuf
S
,
Yusuf
S
,
Pitt
B
,
Davis
CE
,
Hood
WB
,
Cohn
JN
.
Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure
.
N Engl J Med
.
1991
;
325
(
5
):
293
302
.
9.
Granger
CB
,
McMurray
JJ
,
Yusuf
S
,
Held
P
,
Michelson
EL
,
Olofsson
B
, et al.
Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial
.
Lancet
.
2003
;
362
(
9386
):
772
6
.
10.
Hjalmarson
A
,
Goldstein
S
,
Fagerberg
B
,
Wedel
H
,
Waagstein
F
,
Kjekshus
J
, et al.
Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group
.
JAMA
.
2000
;
283
(
10
):
1295
302
.
11.
Packer
M
,
Coats
AJ
,
Fowler
MB
,
Katus
HA
,
Krum
H
,
Mohacsi
P
, et al.
Effect of carvedilol on survival in severe chronic heart failure
.
N Engl J Med
.
2001
;
344
(
22
):
1651
8
.
12.
MERIT-HF Study Group
.
Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)
.
Lancet
.
1999
;
353
(
9169
):
2001
7
.
13.
Flather
MD
,
Shibata
MC
,
Coats
AJ
,
Van Veldhuisen
DJ
,
Parkhomenko
A
,
Borbola
J
, et al.
Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS)
.
Eur Heart J
.
2005
;
26
(
3
):
215
25
.
14.
Pitt
B
,
Zannad
F
,
Remme
WJ
,
Cody
R
,
Castaigne
A
,
Perez
A
, et al.
The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators
.
N Engl J Med
.
1999
;
341
(
10
):
709
17
.
15.
Zannad
F
,
McMurray
JJ
,
Krum
H
,
van Veldhuisen
DJ
,
Swedberg
K
,
Shi
H
, et al.
Eplerenone in patients with systolic heart failure and mild symptoms
.
N Engl J Med
.
2011
;
364
:
11
21
.
16.
CIBIS-II Investigators and Committees
.
The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial
.
Lancet
.
1999
;
353
(
9146
):
9
13
.
17.
Desai
AS
,
Stevenson
LW
.
Rehospitalization for heart failure: predict or prevent
.
Circulation
.
2012
;
126
(
4
):
501
6
.
18.
Greene
SJ
,
Fonarow
GC
,
Vaduganathan
M
,
Khan
SS
,
Butler
J
,
Gheorghiade
M
.
The vulnerable phase after hospitalization for heart failure
.
Nat Rev Cardiol
.
2015
;
12
(
4
):
220
9
.
19.
Cleland
JG
,
Swedberg
K
,
Follath
F
,
Komajda
M
,
Cohen-Solal
A
,
Aguilar
JC
, et al.
The EuroHeart Failure Survey Programme – a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis
.
Eur Heart J
.
2003
;
24
(
5
):
442
63
.
20.
O'Connor
CM
,
Miller
AB
,
Blair
JE
,
Konstam
MA
,
Wedge
P
,
Bahit
MC
, et al.
Causes of death and rehospitalization in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction: results from Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) program
.
Am Heart J
.
2010
;
159
(
5
):
841
e1
.
21.
McMurray
JJ
,
Packer
M
,
Desai
AS
,
Gong
J
,
Lefkowitz
MP
,
Rizkala
AR
, et al.
Angiotensin-neprilysin inhibition versus enalapril in heart failure
.
N Engl J Med
.
2014
;
371
(
11
):
993
1004
.
22.
Ponikowski
P
,
Voors
AA
,
Anker
SD
,
Bueno
H
,
Cleland
JG
,
Coats
AJ
, et al.
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC
.
Eur Heart J
.
2016
;
37
(
27
):
2129
200
.
23.
Yancy
CW
,
Jessup
M
,
Bozkurt
B
,
Butler
J
,
Casey
DE
,
Colvin
MM
, et al.
2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Failure Society of America
.
J Card Fail
.
2017
;
23
(
8
):
628
51
.
24.
Ji
X
,
Cui
N
,
Liu
J
.
Using propensity score matching with doses in observational studies: An example from a child physical abuse and sleep quality study
.
Res Nurs Health
.
2019
;
42
(
6
):
436
45
. .
25.
Blin
P
,
Dureau-Pournin
C
,
Bénichou
J
,
Cottin
Y
,
Mismetti
P
,
Abouelfath
A
, et al.
Comparative real-life effectiveness and safety of dabigatran or rivaroxaban versus vitamin K antagonists: a high-dimensional propensity score matched new users cohort study in the French national healthcare data system SNDS
.
Am J Cardiovasc Drugs
.
2020 Feb
;
20
(
1
):
81
103
. .
26.
Ahmed
A
,
Husain
A
,
Love
TE
,
Gambassi
G
,
Dell'Italia
LJ
,
Francis
GS
, et al.
Heart failure, chronic diuretic use, and increase in mortality and hospitalization: an observational study using propensity score methods
.
Eur Heart J
.
2006
;
27
(
12
):
1431
9
.
27.
Normand
ST
,
Landrum
MB
,
Guadagnoli
E
,
Ayanian
JZ
,
Ryan
TJ
,
Cleary
PD
, et al.
Validating recommendations for coronary angiography following acute myocardial infarction in the elderly: a matched analysis using propensity scores
.
J Clin Epidemiol
.
2001
;
54
(
4
):
387
98
.
28.
Velazquez
EJ
,
Morrow
DA
,
DeVore
AD
,
Duffy
CI
,
Ambrosy
AP
,
McCague
K
, et al.
Angiotensin-neprilysin inhibition in acute decompensated heart failure
.
N Engl J Med
.
2019
;
380
(
6
):
539
48
.
29.
Desai
AS
,
Solomon
SD
,
Shah
AM
,
Claggett
BL
,
Fang
JC
,
Izzo
J
, et al.
Effect of sacubitril-valsartan versus enalapril on aortic stiffness in patients with heart failure and reduced ejection fraction: a randomized clinical trial
.
JAMA
.
2019
:
1
10
. .
30.
Wachter
R
,
Viriato
D
,
Klebs
S
,
Grunow
SS
,
Schindler
M
,
Engelhard
J
, et al.
Early insights into the characteristics and evolution of clinical parameters in a cohort of patients prescribed sacubitril/valsartan in Germany
.
Postgrad Med
.
2018
;
130
(
3
):
308
16
.
31.
De Vecchis
R
,
Paccone
A
,
Di Maio
M
.
Sacubitril/valsartan improves left ventricular longitudinal deformation in heart failure patients with reduced ejection fraction
.
Minerva Cardioangiol
.
2019
;
67
(
6
):
456
63
.
32.
Hollenberg
SM
,
Warner
SL
,
Ahmad
T
,
Amin
VJ
,
Bozkurt
B
,
Butler
J
, et al.
2019 ACC expert consensus decision pathway on risk assessment, management, and clinical trajectory of patients hospitalized with heart failure: a report of the American College of Cardiology Solution Set Oversight Committee
.
J Am Coll Cardiol
.
2019,15
;
74
(
15
):
1966
2011
.
33.
Martens
P
,
Beliën
H
,
Dupont
M
,
Mullens
W
.
Insights into implementation of sacubitril/valsartan into clinical practice
.
ESC Heart Fail
.
2018
;
5
(
3
):
275
83
.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.