Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.
Journal
Circulation
Journal Volume
150
Journal Issue
22
ISSN
1524-4539
Date Issued
2024-11-26
Author(s)
Shaddy, Robert
Burch, Michael
Kantor, Paul F
Solar-Yohay, Susan
Garito, Tania
Zhang, Sijia
Kocun, Michele
Mao, Chad
Cilliers, Antoinette
Wang, Xu
Canter, Charles
Rossano, Joseph
Wallis, Gonzalo
Menteer, Jondavid
Daou, Linda
Kusa, Jacek
Tokel, Kursat
Dilber, Daniel
Xu, Zhuoming
Xiao, Tingting
Halnon, Nancy
Daly, Kevin P
Bock, Matthew J
Zuckerman, Warren
Singh, Tajinder P
Chakrabarti, Manisha
Levitas, Aviva
Senni, Michele
Grutter, Giorgia
Kim, Gi Beom
Song, Jinyoung
Lee, Hyoung Doo
Chen, Ching Kit
Sanchez-de-Toledo, Joan
Law, Yuk
Wanitkun, Suthep
Cui, Yanqin
Anjos, Rui
Mese, Timur
Abstract
BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (N=187) or enalapril (N=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. © 2024 The Authors.
Subjects
enalapril
heart failure
valsartan
ventricular dysfunction, left
Type
journal article