Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2023 May 9;147(19):1436-1443.
doi: 10.1161/CIRCULATIONAHA.122.062557. Epub 2023 Apr 3.

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

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
Affiliations
Multicenter Study

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

Leopoldo Pérez de Isla et al. Circulation. .

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.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT05465278.

Keywords: alirocumab; computed tomography angiography; coronary artery disease; hypercholesterolemia; plaque, atherosclerotic.

PubMed Disclaimer

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.

Figures

Figure.
Figure.
Violin-plot chart showing coronary plaque burden changes (baseline and follow-up) by means of semiautomatic plaque characterization (QAngio CT) in patients with familial hypercholesterolemia treated with alirocumab. Results are shown as median value (interquartile range).
See this image and copyright information in PMC

Comment in

References

    1. Watts GF, Gidding SS, Mata P, Pang J, Sullivan DR, Yamashita S, Raal FJ, Santos RD, Ray KK. Familial hypercholesterolaemia: evolving knowledge for designing adaptive models of care. Nat Rev Cardiol. 2020;17:360–377. doi: 10.1038/s41569-019-0325-8 - PubMed
    1. Kastelein JJP, Ginsberg HN, Langslet G, Kees Hovingh G, Ceska R, Dufour R, Blom D, Civeira F, Krempf M, Lorenzato C, et al. . ODYSSEY FH i and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015;36:2996–3003. doi: 10.1093/eurheartj/ehv370 - PMC - PubMed
    1. Alonso R, Muñiz-Grijalvo O, Díaz-Díaz JL, Zambón D, de Andrés R, Arroyo-Olivares R, Fuentes-Jimenez F, Muñoz-Torrero JS, Cepeda J, Aguado R, et al. ; SAFEHEART investigators. Efficacy of PCSK9 inhibitors in the treatment of heterozygous familial hypercholesterolemia: A clinical practice experience. J Clin Lipidol. 2021;15:584–592. doi: 10.1016/j.jacl.2021.04.011 - PubMed
    1. Räber L, Ueki Y, Otsuka T, Losdat S, Häner JD, Lonborg J, Fahrni G, Iglesias JF, van Geuns R-J, Ondracek AS, et al. ; PACMAN-AMI collaborators. Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infarction. JAMA. 2022;327:1771–1781. doi: 10.1001/jama.2022.5218 - PMC - PubMed
    1. Pérez de Isla L, Alonso R, Muñiz-Grijalvo O, Díaz-Díaz JL, Zambón D, Miramontes JP, Fuentes F, Gómez de Diego JJ, González-Estrada A, Mata N, et al. . Coronary computed tomographic angiography findings and their therapeutic implications in asymptomatic patients with familial hypercholesterolemia. Lessons from the SAFEHEART study. J Clin Lipidol. 2018;12:948–957. doi: 10.1016/j.jacl.2018.04.003 - PubMed

Publication types

MeSH terms

Substances

Associated data