Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study
Abstract
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.
Conflict of interest statement
Disclosures Dr Pérez de Isla received research grants, speaker fees, and consultant fees from Sanofi and Amgen. Dr Díaz-Díaz received research grants, speaker fees, and consultant fees from Sanofi, Amgen, and Daichii-Sankyo. Dr Romero received research grants, speaker fees, and consultant fees from Sanofi and Amgen. Dr Muñiz-Grijalvo received speaker fees from Sanofi and Amgen. Dr Argüeso received research grants, speaker fees, and consultant fees from Sanofi and Amgen. Dr Muñóz-Torrero received research grants, speaker fees, and consultant fees from Sanofi and Amgen. Dr Suárez received speaker fees from Sanofi and Amgen. Dr Casañas received speaker fees from Sanofi. Dr Fuentes received research grants, speaker fees, and consultant fees from Sanofi and Amgen. Dr Guijarro received personal fees from Amgen and Sanofi. Dr Saltijeral Cerezo received research grants, speaker fees, and consultant fees from Sanofi and Amgen. Dr Mata received research grants from Sanofi and Amgen. Drs Mediavilla, Rubio, Álvarez-Baños, Ponte, Mañas, Cepeda, Barba, and Padró report no conflicts of interest.
Link: https://pubmed.ncbi.nlm.nih.gov/37009731/
Date: 2023 May 9
Sources: Circulation.
- PMID: 37009731
- PMCID: PMC10158600
- DOI: 10.1161/CIRCULATIONAHA.122.062557
Authors: Leopoldo Pérez de Isla 1, Jose L Díaz-Díaz 2, Manuel J Romero 3, Ovidio Muñiz-Grijalvo 4, Juan D Mediavilla 5, Rosa Argüeso 6, Juan F Sánchez Muñoz-Torrero 7, Patricia Rubio 8, Pilar Álvarez-Baños 9, Paola Ponte 10, Dolores Mañas 11, Lorena Suárez Gutierrez 12, José María Cepeda 13, Marta Casañas 14, Francisco Fuentes 15, Carlos Guijarro 16, Miguel Ángel Barba 17, Adriana Saltijeral Cerezo 18, Teresa Padró 19, Pedro Mata 20; SAFEHEART Study Group
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