Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia : The ARCHITECT Study
Pérez de Isla, Leopoldo (Hospital Universitario Clínico San Carlos (Madrid))
Diaz-Diaz, Jose Luis (Hospital Abente y Lago (A Coruña, Galícia))
Romero-Jiménez, Manuel Jesús (Hospital Infanta Elena (Huelva, Andalusia))
Muniz Grijalvo, Ovidio (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Mediavilla, Juan D. (Hospital Universitario Virgen de las Nieves (Granada))
Argueso, Rosa (Hospital Universitario Lucus Augusti (Lugo))
Sanchez Munoz-Torrero, Juan F. (Hospital San Pedro de Alcántara (Càceres))
Rubio Marín, Patricia (Hospital Universitario Jerez de la Frontera)
Alvarez-Banos, Pilar (Hospital Universitario de Burgos)
Ponte Márquez, Paola H (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Manas, Dolores (Hospital General Universitario de Ciudad Real)
Suarez Gutierrez, Lorena (Hospital Universitario Central de Asturias)
Cepeda, José María (Hospital Comarcal Vega Baja (Alacant))
Casanas, Marta (Hospital Universitario San Pedro (La Rioja))
Fuentes Jiménez, Francisco (Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición)
Guijarro, Carlos (Hospital Universitario Fundación Alcorcón)
Barba Romero, Miguel Ángel (Complejo Hospitalario Universitario (Albacete))
Saltijeral Cerezo, Adriana (Hospital Vithas Aravaca (Madrid))
Padró, Teresa (Institut d'Investigació Biomèdica Sant Pau)
Mata, Pedro (Fundacion Hipercolesterolemia Familiar (Madrid))
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	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. 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. 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). 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. URL: https://www. clinicaltrials. gov; Unique identifier: NCT05465278.
Grants:	Ministerio de Economía y Competitividad PI12/01289 Instituto de Salud Carlos III PI17/01320
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alirocumab ; Atherosclerotic ; Computed tomography angiography ; Coronary artery disease ; Hypercholesterolemia ; Plaque
Published in:	Circulation, Vol. 147 Núm. 19 (september 2023) , p. 1436-1443, ISSN 1524-4539

DOI: 10.1161/CIRCULATIONAHA.122.062557
PMID: 37009731

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