Pérez de Isla, Leopoldo Díaz-Díaz, José Luis Romero, Manuel J. Muñiz-Grijalvo, Ovidio Mediavilla, Juan D. Argüeso, Rosa Sánchez Muñoz-Torrero, Juan Rubio, Patricia Álvarez-Baños, Pilar Ponte, Paola Mañas, María Dolores Suárez Gutierrez, Lorena Cepeda, José María Casañas, Marta Fuentes, Francisco Guijarro, Carlos Barba, Miguel A. Saltijeral Cerezo, Adriana Padró, Teresa Mata, Pedro 2025-03-07T10:58:51Z 2025-03-07T10:58:51Z 2023 http://hdl.handle.net/10396/32579 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. application/pdf eng American Heart Association https://creativecommons.org/licenses/by-nc-nd/4.0/ Pérez De Isla, L., Díaz-Díaz, J. L., Romero, M. J., Muñiz-Grijalvo, O., Mediavilla, J. D., Argüeso, R., Muñoz-Torrero, J. F. S., Rubio, P., Álvarez-Baños, P., Ponte, P., Mañas, D., Gutierrez, L. S., Cepeda, J. M., Casañas, M., Fuentes, F., Guijarro, C., Barba, M. Á., Cerezo, A. S., Padró, T., & Mata, P. (2023). Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study. Circulation, 147(19), 1436-1443. https://doi.org/10.1161/circulationaha.122.062557 Alirocumab Computed tomography angiography Coronary artery disease Hypercholesterolemia Plaque Atherosclerotic Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study info:eu-repo/semantics/article https://doi.org/10.1161/CIRCULATIONAHA.122.062557 info:eu-repo/semantics/openAccess