Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
Por:
de Isla, LP, Diaz-Diaz, JL, Romero, MJ, Muniz-Grijalvo, O, Mediavilla, JD, Argueso, R, Munoz-Torrero, JS, Rubio, P, Alvarez-Banos, P, Ponte, P, Manas, D, Gutierrez, LS, Cepeda, JM, Casanas, M, Fuentes, F, Guijarro, C, Barba, MA, Cerezo, AS, Padro, T, Mata, P, SAFEHEART Study Grp
Publicada:
9 may 2023
Ahead of Print:
3 abr 2023
Resumen:
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.
Filiaciones:
de Isla, LP:
Clin San Carlos Univ Hosp, Cardiol Dept, Madrid, Spain
Hosp Clin San Carlos, Serv Cardiol, C Prof Martin Lagos S-N, Madrid 28040, Spain
Diaz-Diaz, JL:
Hosp Abente y Lago, Internal Med Dept, La Coruna, Spain
Hosp Comarcal Vega Baja, Internal Med Dept, Orihuela, Alicante, Spain
Romero, MJ:
Hosp Infanta Elena, Internal Med Dept, Huelva, Spain
Muniz-Grijalvo, O:
Hosp Virgen del Rocio, Internal Med Dept, Seville, Spain
Mediavilla, JD:
Hosp Univ Virgen de las Nieves, Internal Med Dept, Granada, Spain
Argueso, R:
Hosp Univ Lucus Augusti, Endocrinol Dept, Lugo, Spain
Munoz-Torrero, JS:
Hosp San Pedro de Alcantara, Internal Med Dept, Caceres, Spain
Rubio, P:
Hosp Univ Jerez de la Frontera, Internal Med Dept, Cadiz, Spain
Alvarez-Banos, P:
Hosp Univ Burgos, Endocrinol Dept, Burgos, Spain
Ponte, P:
Hosp Santa Creu i St Pau, Internal Med Dept, Barcelona, Spain
Manas, D:
Hosp Gen Univ Ciudad Real, Internal Med Dept, Ciudad Real, Spain
Gutierrez, LS:
Hosp Cent Asturias, Endocrinol Dept, Oviedo, Spain
Casanas, M:
Hosp San Pedro, Internal Med Dept, Logrono, Spain
Fuentes, F:
Hosp Univ Reina Sofia, Lipid & Atherosclerosis Unit, CIBERObn, IMBIC, Cordoba, Argentina
Guijarro, C:
Univ Rey Juan Carlos, Hosp Univ Fdn Alcorcon, Internal Med Dept, Madrid, Spain
Barba, MA:
Complejo Hosp Univ, Internal Med Dept, Albacete, Spain
Cerezo, AS:
Hosp Vithas Aravaca, Cardiol Dept, Madrid, Spain
Padro, T:
IIB St Pau, Inst Recerca Hosp Santa Creu & St Pau, Programa ICCC Cardiovasc, CIBERCV, Barcelona, Spain
Mata, P:
Fdn Hipercolesterolemia Familiar, C Gen Alvarez de Castro 14,Primero E, Madrid E-28010, Spain
Green Published, hybrid, All Open Access, Hybrid Gold, Green
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