Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial
Issued Date
2024-11-26
Resource Type
ISSN
00097322
eISSN
15244539
Scopus ID
2-s2.0-85205391068
Pubmed ID
39319469
Journal Title
Circulation
Volume
150
Issue
22
Start Page
1756
End Page
1766
Rights Holder(s)
SCOPUS
Bibliographic Citation
Circulation Vol.150 No.22 (2024) , 1756-1766
Suggested Citation
Shaddy R., Burch M., Kantor P.F., Solar-Yohay S., Garito T., Zhang S., Kocun M., Mao C., Cilliers A., Wang X., Canter C., Rossano J., Wallis G., Menteer J., Daou L., Kusa J., Tokel K., Dilber D., Xu Z., Xiao T., Halnon N., Daly K.P., Bock M.J., Zuckerman W., Singh T.P., Chakrabarti M., Levitas A., Senni M., Grutter G., Kim G.B., Song J., Lee H.D., Chen C.K., Sanchez-De-Toledo J., Law Y., Wanitkun S., Cui Y., Anjos R., Mese T., Bonnet D., Ablonczy L., Aggarwal N., Agnoletti G., Alhabdan M., Amedro P., Ameduri R., Alberto Annoni G., Asante-Korang A., Audi N., Ballweg J., Berger F., Bosaleh M., Boyle G., Castaldi B., Chag M., Chaloupecky V., Chehab G., Conway J., Daehnert I., Di Bernardo S., Dittrich S., Dogan E., Donti A., Durongpisitkul K., Favilli S., Feingold B., Garcia-Guereta L., Gil-Villanueva N., Glass L., Gomez-Guzman E., Gorenflo M., Gran F., Hirata Y., Hirono K., Hoshino K., Hsieh K.S., Hussain M., Inuzuka R., Ishido M., Jeewa A., Johnson J., Jokinen E., Won Jung J., Kaneva-Nencheva A., Kaufman B., Kochilas L., Kumar S., Lal A., Viktorovna Leontyeva I., Lin I.C., Lytrivi I., Malcic I., Marinho Da Silva A., Medrano Lopez C., Milanesi O., Deanne Miyamoto S., Motomura H., Odri Komazec I., Ono H., Pacileo G. Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial. Circulation Vol.150 No.22 (2024) , 1756-1766. 1766. doi:10.1161/CIRCULATIONAHA.123.066605 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/102286
Title
Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial
Author(s)
Shaddy R.
Burch M.
Kantor P.F.
Solar-Yohay S.
Garito T.
Zhang S.
Kocun M.
Mao C.
Cilliers A.
Wang X.
Canter C.
Rossano J.
Wallis G.
Menteer J.
Daou L.
Kusa J.
Tokel K.
Dilber D.
Xu Z.
Xiao T.
Halnon N.
Daly K.P.
Bock M.J.
Zuckerman W.
Singh T.P.
Chakrabarti M.
Levitas A.
Senni M.
Grutter G.
Kim G.B.
Song J.
Lee H.D.
Chen C.K.
Sanchez-De-Toledo J.
Law Y.
Wanitkun S.
Cui Y.
Anjos R.
Mese T.
Bonnet D.
Ablonczy L.
Aggarwal N.
Agnoletti G.
Alhabdan M.
Amedro P.
Ameduri R.
Alberto Annoni G.
Asante-Korang A.
Audi N.
Ballweg J.
Berger F.
Bosaleh M.
Boyle G.
Castaldi B.
Chag M.
Chaloupecky V.
Chehab G.
Conway J.
Daehnert I.
Di Bernardo S.
Dittrich S.
Dogan E.
Donti A.
Durongpisitkul K.
Favilli S.
Feingold B.
Garcia-Guereta L.
Gil-Villanueva N.
Glass L.
Gomez-Guzman E.
Gorenflo M.
Gran F.
Hirata Y.
Hirono K.
Hoshino K.
Hsieh K.S.
Hussain M.
Inuzuka R.
Ishido M.
Jeewa A.
Johnson J.
Jokinen E.
Won Jung J.
Kaneva-Nencheva A.
Kaufman B.
Kochilas L.
Kumar S.
Lal A.
Viktorovna Leontyeva I.
Lin I.C.
Lytrivi I.
Malcic I.
Marinho Da Silva A.
Medrano Lopez C.
Milanesi O.
Deanne Miyamoto S.
Motomura H.
Odri Komazec I.
Ono H.
Pacileo G.
Burch M.
Kantor P.F.
Solar-Yohay S.
Garito T.
Zhang S.
Kocun M.
Mao C.
Cilliers A.
Wang X.
Canter C.
Rossano J.
Wallis G.
Menteer J.
Daou L.
Kusa J.
Tokel K.
Dilber D.
Xu Z.
Xiao T.
Halnon N.
Daly K.P.
Bock M.J.
Zuckerman W.
Singh T.P.
Chakrabarti M.
Levitas A.
Senni M.
Grutter G.
Kim G.B.
Song J.
Lee H.D.
Chen C.K.
Sanchez-De-Toledo J.
Law Y.
Wanitkun S.
Cui Y.
Anjos R.
Mese T.
Bonnet D.
Ablonczy L.
Aggarwal N.
Agnoletti G.
Alhabdan M.
Amedro P.
Ameduri R.
Alberto Annoni G.
Asante-Korang A.
Audi N.
Ballweg J.
Berger F.
Bosaleh M.
Boyle G.
Castaldi B.
Chag M.
Chaloupecky V.
Chehab G.
Conway J.
Daehnert I.
Di Bernardo S.
Dittrich S.
Dogan E.
Donti A.
Durongpisitkul K.
Favilli S.
Feingold B.
Garcia-Guereta L.
Gil-Villanueva N.
Glass L.
Gomez-Guzman E.
Gorenflo M.
Gran F.
Hirata Y.
Hirono K.
Hoshino K.
Hsieh K.S.
Hussain M.
Inuzuka R.
Ishido M.
Jeewa A.
Johnson J.
Jokinen E.
Won Jung J.
Kaneva-Nencheva A.
Kaufman B.
Kochilas L.
Kumar S.
Lal A.
Viktorovna Leontyeva I.
Lin I.C.
Lytrivi I.
Malcic I.
Marinho Da Silva A.
Medrano Lopez C.
Milanesi O.
Deanne Miyamoto S.
Motomura H.
Odri Komazec I.
Ono H.
Pacileo G.
Author's Affiliation
Pusan National University Yangsan Hospital
Ramathibodi Hospital
University of Health Sciences
Seattle Children's Hospital
UCLA Mattel Children's Hospital
Université Paris Cité
Seoul National University Children's Hospital
Hospital Sant Joan de Déu Barcelona
Regional Specialist Hospital, Wroclaw
Shanghai Children's Medical Center
Hôtel-Dieu de France Hospital
KBC Zagreb
Soroka University Medical Center
The Children's Hospital of Philadelphia
Chris Hani Baragwanath Hospital
Loma Linda University Children's Hospital
Başkent Üniversitesi
Columbia University Irving Medical Center
Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
NUS Yong Loo Lin School of Medicine
Washington University School of Medicine in St. Louis
Samsung Medical Center, Sungkyunkwan university
Indraprastha Apollo Hospitals
Great Ormond Street Hospital for Children NHS Foundation Trust
IRCCS Ospedale Pediatrico Bambino Gesù
Hospital de Santa Cruz, Carnaxide
Keck School of Medicine of USC
Università degli Studi di Milano-Bicocca
Novartis International AG
Harvard Medical School
Emory University
Guangzhou Women and Children's Medical Center
Children’s Hospital of Shanghai
Novartis
Levine Children's Hospital
Ramathibodi Hospital
University of Health Sciences
Seattle Children's Hospital
UCLA Mattel Children's Hospital
Université Paris Cité
Seoul National University Children's Hospital
Hospital Sant Joan de Déu Barcelona
Regional Specialist Hospital, Wroclaw
Shanghai Children's Medical Center
Hôtel-Dieu de France Hospital
KBC Zagreb
Soroka University Medical Center
The Children's Hospital of Philadelphia
Chris Hani Baragwanath Hospital
Loma Linda University Children's Hospital
Başkent Üniversitesi
Columbia University Irving Medical Center
Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
NUS Yong Loo Lin School of Medicine
Washington University School of Medicine in St. Louis
Samsung Medical Center, Sungkyunkwan university
Indraprastha Apollo Hospitals
Great Ormond Street Hospital for Children NHS Foundation Trust
IRCCS Ospedale Pediatrico Bambino Gesù
Hospital de Santa Cruz, Carnaxide
Keck School of Medicine of USC
Università degli Studi di Milano-Bicocca
Novartis International AG
Harvard Medical School
Emory University
Guangzhou Women and Children's Medical Center
Children’s Hospital of Shanghai
Novartis
Levine Children's Hospital
Corresponding Author(s)
Other Contributor(s)
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.