Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study

Background: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment wi...

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Autores: Perez De Isla, L., Díaz Díaz, José Luis, Romero, M.J., Muniz-Grijalvo, O., Mediavilla, J.D., Argueso, R., Sanchez Munoz-Torrero, J.F., Rubio, P., Alvarez-Banos, P., Ponte, P., Manas, D., Suarez Gutierrez, L., Cepeda, J.M., Casanas, M., Fuentes, F., Guijarro, C., Angel Barba, M., Saltijeral Cerezo, A., Padro, T., Mata, P.
Formato: artículo
Fecha de publicación:2023
País:España
Recursos:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21039
Acesso em linha:https://portalcientifico.sergas.gal//documentos/647346d1c0b3b1384998827f
http://hdl.handle.net/20.500.11940/21039
Access Level:acceso abierto
Palavra-chave:Humans
Female
Middle Aged
Male
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Proprotein Convertase 9
Coronary Artery Disease
Hypercholesterolemia
Plaque, Atherosclerotic
Hyperlipoproteinemia Type II
Atherosclerosis
Acute Coronary Syndrome
Treatment Outcome
AS A Coruña
CHUAC
id ES_7f1be90bdb3fee25b9e3d8ea258c8993
oai_identifier_str oai:runa.sergas.gal:20.500.11940/21039
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
title Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
spellingShingle Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
Perez De Isla, L.
Humans
Female
Middle Aged
Male
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Proprotein Convertase 9
Coronary Artery Disease
Hypercholesterolemia
Plaque, Atherosclerotic
Hyperlipoproteinemia Type II
Atherosclerosis
Acute Coronary Syndrome
Treatment Outcome
AS A Coruña
CHUAC
title_short Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
title_full Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
title_fullStr Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
title_full_unstemmed Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
title_sort Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
dc.creator.none.fl_str_mv Perez De Isla, L.
Díaz Díaz, José Luis
Romero, M.J.
Muniz-Grijalvo, O.
Mediavilla, J.D.
Argueso, R.
Sanchez Munoz-Torrero, J.F.
Rubio, P.
Alvarez-Banos, P.
Ponte, P.
Manas, D.
Suarez Gutierrez, L.
Cepeda, J.M.
Casanas, M.
Fuentes, F.
Guijarro, C.
Angel Barba, M.
Saltijeral Cerezo, A.
Padro, T.
Mata, P.
author Perez De Isla, L.
author_facet Perez De Isla, L.
Díaz Díaz, José Luis
Romero, M.J.
Muniz-Grijalvo, O.
Mediavilla, J.D.
Argueso, R.
Sanchez Munoz-Torrero, J.F.
Rubio, P.
Alvarez-Banos, P.
Ponte, P.
Manas, D.
Suarez Gutierrez, L.
Cepeda, J.M.
Casanas, M.
Fuentes, F.
Guijarro, C.
Angel Barba, M.
Saltijeral Cerezo, A.
Padro, T.
Mata, P.
author_role author
author2 Díaz Díaz, José Luis
Romero, M.J.
Muniz-Grijalvo, O.
Mediavilla, J.D.
Argueso, R.
Sanchez Munoz-Torrero, J.F.
Rubio, P.
Alvarez-Banos, P.
Ponte, P.
Manas, D.
Suarez Gutierrez, L.
Cepeda, J.M.
Casanas, M.
Fuentes, F.
Guijarro, C.
Angel Barba, M.
Saltijeral Cerezo, A.
Padro, T.
Mata, P.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Humans
Female
Middle Aged
Male
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Proprotein Convertase 9
Coronary Artery Disease
Hypercholesterolemia
Plaque, Atherosclerotic
Hyperlipoproteinemia Type II
Atherosclerosis
Acute Coronary Syndrome
Treatment Outcome
AS A Coruña
CHUAC
topic Humans
Female
Middle Aged
Male
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Proprotein Convertase 9
Coronary Artery Disease
Hypercholesterolemia
Plaque, Atherosclerotic
Hyperlipoproteinemia Type II
Atherosclerosis
Acute Coronary Syndrome
Treatment Outcome
AS A Coruña
CHUAC
description Background: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. Methods: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. Results: The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (P<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). Conclusions: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://portalcientifico.sergas.gal//documentos/647346d1c0b3b1384998827f
http://hdl.handle.net/20.500.11940/21039
url https://portalcientifico.sergas.gal//documentos/647346d1c0b3b1384998827f
http://hdl.handle.net/20.500.11940/21039
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas
instname:Servizo Galego de Saúde (SERGAS)
instname_str Servizo Galego de Saúde (SERGAS)
reponame_str RUNA. Repositorio da Consellería de Sanidade e Sergas
collection RUNA. Repositorio da Consellería de Sanidade e Sergas
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT StudyPerez De Isla, L.Díaz Díaz, José LuisRomero, M.J.Muniz-Grijalvo, O.Mediavilla, J.D.Argueso, R.Sanchez Munoz-Torrero, J.F.Rubio, P.Alvarez-Banos, P.Ponte, P.Manas, D.Suarez Gutierrez, L.Cepeda, J.M.Casanas, M.Fuentes, F.Guijarro, C.Angel Barba, M.Saltijeral Cerezo, A.Padro, T.Mata, P.HumansFemaleMiddle AgedMaleHydroxymethylglutaryl-CoA Reductase InhibitorsProprotein Convertase 9Coronary Artery DiseaseHypercholesterolemiaPlaque, AtheroscleroticHyperlipoproteinemia Type IIAtherosclerosisAcute Coronary SyndromeTreatment OutcomeAS A CoruñaCHUACBackground: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. Methods: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. Results: The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (P<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). Conclusions: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.This study was supported by Fundacion Hipercolesterolemia Familiar; grant G03/181, FIS PI12/01289 and ISCIII PI17/01320 from Instituto de Salud Carlos III (ISCIII), grant 08-2008 Centro Nacional de Investigacion Cardiovascular (CNIC), and an unrestricted grant from Sanofi.2023info:eu-repo/semantics/articlehttps://portalcientifico.sergas.gal//documentos/647346d1c0b3b1384998827fhttp://hdl.handle.net/20.500.11940/21039reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttps://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/210392026-06-12T08:40:47Z
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