Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure
Authors: J O&#x27;Neill
J McGinty
G Lancaster
C Kunavarapu
Carol I Duffy
A Kabour
Abby Cange
R Schofield
P Heydorn
M Danyaal
F Jadbabaie
M Finkel
A Mahmood
D O&#x27;Rourke
S Rizvi
H Kashou
K Ramasubbu
A Sauer
C Lang
T Kanaan
N Jaffrani
D Weinstein
K Tong
A Valika
F Ghazi
Laura Grip
V Fernandes
M Krantz
L Grazette
B Muneer
A Deramo
J Tauras
B Jaski
Kevin McCague
B Schietinger
Gary S Francis
J Tallaj
T Gong
S Hankins
J Welker
M Leonen
Polly Fish
Yared Gurmu
R Long
A Garan
C DuBois
Andrew P Ambrosy
J Canto
D Hinchman
F Franchi
P Deedwania
J Finet
Marc Sabatine
S Vallurupalli
A Shehadeh
B Pisani
S Hall
V Kumar
J Muldowney 3rd
S Kindsvater
I Dumitru
H Cha
C Cosgrove
T Ward
D Vaz
T Chinnadurai
H Alhosaini
H Ooi
Kent R Bailey
M Rummel
J Balacko
R Dhingra
K Adams
Bruce L Zuraw
L Forgosh
J Thibodeau
D Angiolillo
R Ray
W Nelson
Shannon Doerfler
G Blair
K Vakil
E Gharib
C Lambert
R Palac
E Crebo
Adrian F Hernandez
Z Mirza
J Joseph
Allen P Kaplan
T Zynda
PIONEER-HF Investigators
J Vilaro
Nancy J Brown
G Conrad
C Schmalfuss
S Hafer
B Bozkurt
G Mullen
David A Morrow
C Rogell
L Musto
S Dani
S Motiwala
M Hoffmann
N Haglund
R Prasad
S Enoru
V Rao
J Larned
D Talreja
S Rennyson
P Stockwell
A Adler
S Rao
S Gips
J Izzo
Hrishikesh Chakraborty
K Axsom
J Radojevic
S Lamba
K Laventure
F Rajput
J Go
D Levine
D Banerjee
D Lombardo
S Lin
D Bloomfield
M Gelernt
J Wight
A Misra
F Mody
M Koren
D Haithcock
V Nadar
Julie Samia
K Browne
V Srinivasan
G Larrain
C Wolford
P Carson
A Adjei
Gregg C Fonarow
M Sabe
B Howard
R Perlman
S Pinney
Eric J Velazquez
Heather Wood
S Sharma
Patty Darragh
C Bhardwaj
S Skaluba
R Jermyn
B Tunney
J Lyons
P Gandhi
D Lenihan
A Abbate
D Haas
L Brookfield
J Ullman
Mary Ann Sellers
D Karia
K Shemisa
G Wohlford
Eugene Braunwald
K Reedy
K Pandya
M Pham
W Zhou
R Zolty
K Chandrasekhar
K Heilman
B Uretsky
W Leimbach
N Buljubasic
M Saltzberg
J Heitner
D Moraes
J Harris
H Morsli
M Costanzo
Ricardo Rocha
F Sogade
D Pauly
M Montpetit
J Kennedy
A Van Bakel
R Gelzer-Bell
T To
S Patel
W Wickemeyer
G Stevens
R Kode
D Westerhausen
D Henderson
W Gray
T O&#x27;Brien
S Feitell
Adam D DeVore
M Moscucci
K Masri
I Dauber
R Yaryura
M Bernstein
J Anderson
S Khosla
J Wilburn
J Smith
Journal: New England Journal of Medicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: acute decompensated heart failure; sacubitril-valsartan therapy; hospitalized patients; reduced ejection fraction; NT-proBNP concentration
Affiliations: From the Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT (E.J.V.); the Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston (D.A.M., E.B.); Duke Clinical Research Institute, Duke University, Durham, NC (A.D.D.); Novartis Pharmaceuticals, East Hanover, NJ (C.I.D., K.M., R.R.); and the Division of Cardiology, Permanente Medical...

Abstract:  Background: Acute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril-valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown. Methods: We enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily). The primary efficacy outcome was the time-averaged proportional change in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline through weeks 4 and 8. Key safety outcomes were the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema. Results: Of the 881 patients who underwent randomization, 440 were assigned to receive sacubitril-valsartan and 441 to receive enalapril. The time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril-valsartan group than in the enalapril group; the ratio of the geometric mean of values obtained at weeks 4 and 8 to the baseline value was 0.53 in the sacubitril-valsartan group as compared with 0.75 in the enalapril group (percent change, -46.7% vs. -25.3%; ratio of change with sacubitril-valsartan vs. enalapril, 0.71; 95% confidence interval [CI], 0.63 to 0.81; P&lt;0.001). The greater reduction in the NT-proBNP concentration with sacubitril-valsartan than with enalapril was evident as early as week 1 (ratio of change, 0.76; 95% CI, 0.69 to 0.85). The rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. Conclusions: Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril-valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy. Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. (Funded by Novartis; PIONEER-HF ClinicalTrials.gov number, NCT02554890 .). 

Retracted: No

PubPeer comments:
 In the published PIONEER-HF study there is an impressive difference in NT-proBNP between the two studied groups of patients with acute heart failure. Notably the greatest difference was achieved in their first week of treatment. The studied groups seem to be well balanced in terms of patients characteristics, however it is not clear why only patients in the Sacubitril Valsartan and not also the Enalapril group had a u201cwashout periodu201d of a minimum of 36 hours. This could potentially confound the results u2013 are we possibly comparing patients that tolerated higher doses of intravenous diuretics and intravenous vasodilators (Sacubitril Valsartan group) with patients that would not tolerate higher doses due to the blood-pressure lowering effects of a  immediate HF-therapyu201c (Enalapril group)? Disclosing the mean diuretic dose or the average weight loss in the first week would help to clarify this question. ,