Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments

Detalhes bibliográficos
Autor(a) principal: Agarwal, Anupam
Data de Publicação: 2022
Outros Autores: Farfel, Gail M., Gammaitoni, Arnold R., Wong, Pierre C., Pinto, Fausto J., Galer, Bradley S.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/53463
Resumo: © 2022 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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spelling Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessmentsDravet syndromeEchocardiographyFenfluramineLong-termSafety© 2022 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Objective: To assess the cardiovascular safety of fenfluramine when used to treat children and young adults with Dravet syndrome. Methods: Patients with Dravet syndrome who completed one of three phase 3 clinical trials of fenfluramine could enroll in the open-label extension (OLE) study (NCT02823145). All patients started fenfluramine treatment at an oral dose of 0.2 mg/kg/day. The dose was titrated based on efficacy and tolerability to a maximum of 0.7 mg/kg/day (absolute maximum 26 mg/day) or 0.4 mg/kg/day (absolute maximum 17 mg/day) in patients concomitantly receiving stiripentol. Serial transthoracic echocardiography was performed using standardized methods and blinded readings at OLE entry, after 4-6 weeks, and every 3 months thereafter. Valvular heart disease (VHD) was defined as ≥ moderate mitral regurgitation or ≥ mild aortic regurgitation combined with physical signs or symptoms attributable to valve dysfunction. Pulmonary artery hypertension (PAH) was defined as systolic pulmonary artery pressure >35 mmHg. Results: A total of 327 patients (median age, 9.0 years; range, 2-19 years) have enrolled in the OLE and received ≥1 dose of fenfluramine. The median duration of treatment was 23.9 months (range, 0.2-42.6 months) and the median dose of fenfluramine was 0.44 mg/kg/day. No patient demonstrated VHD or PAH at any time during the OLE. Significance/interpretation: This study, which represents the largest, longest, and most rigorous examination of cardiovascular safety of fenfluramine yet reported, found no cases of VHD or PAH. These results, combined with fenfluramine's substantial antiseizure efficacy, support a strong positive benefit-risk profile for fenfluramine in the treatment of Dravet syndrome.ElsevierRepositório da Universidade de LisboaAgarwal, AnupamFarfel, Gail M.Gammaitoni, Arnold R.Wong, Pierre C.Pinto, Fausto J.Galer, Bradley S.2022-06-23T16:39:52Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53463engEur J Paediatr Neurol. 2022 May 24;39:35-391090-379810.1016/j.ejpn.2022.05.0061532-2130info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:59:14Zoai:repositorio.ul.pt:10451/53463Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:24.285098Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments
title Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments
spellingShingle Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments
Agarwal, Anupam
Dravet syndrome
Echocardiography
Fenfluramine
Long-term
Safety
title_short Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments
title_full Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments
title_fullStr Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments
title_full_unstemmed Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments
title_sort Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments
author Agarwal, Anupam
author_facet Agarwal, Anupam
Farfel, Gail M.
Gammaitoni, Arnold R.
Wong, Pierre C.
Pinto, Fausto J.
Galer, Bradley S.
author_role author
author2 Farfel, Gail M.
Gammaitoni, Arnold R.
Wong, Pierre C.
Pinto, Fausto J.
Galer, Bradley S.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Agarwal, Anupam
Farfel, Gail M.
Gammaitoni, Arnold R.
Wong, Pierre C.
Pinto, Fausto J.
Galer, Bradley S.
dc.subject.por.fl_str_mv Dravet syndrome
Echocardiography
Fenfluramine
Long-term
Safety
topic Dravet syndrome
Echocardiography
Fenfluramine
Long-term
Safety
description © 2022 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
publishDate 2022
dc.date.none.fl_str_mv 2022-06-23T16:39:52Z
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/53463
url http://hdl.handle.net/10451/53463
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Eur J Paediatr Neurol. 2022 May 24;39:35-39
1090-3798
10.1016/j.ejpn.2022.05.006
1532-2130
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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