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Data from the ARCHITECT trial detail the effects of alirocumab use on coronary plaque burden and characteristics in a cohort of patients with familial hypercholesterolemia but without atherosclerotic cardiovascular disease.
New data from the ARCHITECT study provides an overview of the effects of alirocumab on coronary plaque burden in patients with familial hypercholesterolemia.
Results of the study, which was a phase 4, open-label, single-arm trial, indicate use of alirocumab significantly reduced both LDL-C and coronary plaque burden, with additional analyses shedding light on the specific effects on different markers of atherosclerosis.
“This study shows how treatment with PCSK9 inhibitor alirocumab, in addition to high-intensity statin therapy, resulted in significant regression of coronary PB and plaque stabilization on coronary CTA over 78 weeks in patients with FH without clinical [atherosclerotic cardiovascular disease],” wrote investigators.
Published less than a month after results of the YELLOW III study provided insight into the effects of evolocumab on clinical plaque morphology2, results of the ARCHITECT trial offer a more in-depth understanding of the effects of PSCK9 inhibitor use on plaque characteristics. Unlike YELLOW III, which enrolled patients with stable coronary artery disease, the ARCHITECT study enrolled a population of asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe and was designed with the intent of exploring changes in coronary plaque burden over a 78-week period.1
A phase 4, single-arm trial, the study was completed by 104 individuals. Of note, all individuals included in the study were enrolled within the SAFEHEART registry. This cohort had a median age of 53.3 (IQR, 46.2-59.4) years, 51.9% were women, the median LDL-C at baseline was 138.9 (117.5-175.3) mg/dL, and the median coronary plaque burden was 34.6% (32.5-37.8).1
Per study protocol, every patient received 150 mg of alirocumab subcutaneously every 14 days in addition to high-intensity statin therapy. The primary outcome of interest for the study was the change in coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree via coronary computed tomographic angiography.1
Upon analysis, results suggested the median LDL-C level decreased from 138.9 (117.5-175.3) mg/dL at entry to 45.0 (36-65.0) mg/dL at follow-up (P <.001), which investigators pointed out a 67.6% median relative percentage reduction. Further analysis indicated the coronary plaque burden changed from 34.6% (32.5-36.8) at entry to 30.4% (27.4-33.4) at follow-up (P <.001).1
In regard to plaque characteristics, investigators found significant change during the study. Specifically, investigators observed an increase in the proportion of calcified (+0.3%; P <.001) and mainly fibrous (+6.2%; P <.001) plaque. In contrast, a decrease was observed for the percentage of fibro-fatty (-3.9%; P <.001) and necrotic plaque (-0.6%; P <.001). According to the SAFEHEART risk equation, the median 10-year cardiovascular risk score decreased from 0.68% (0.35-1.02) at enrollment to 0.22% (0.09-0.35) after follow-up.1
When assessing safety profile of alirocumab, investigators identified adverse events among 14% of the cohort. Although none of these events were severe, 6 patients reported mild and transient myalgia, 5 patients reported mild and transient allergic reactions, 2 patients reported injection site reaction, and 2 patients reported flu-like syndrome. Investigators pointed out none of these events were a reason for discontinuation of the study or medication.1
“ARCHITECT provides crucial mechanistic clues on coronary plaque behavior under the use of alirocumab, and its results could link and explain ODYSSEY OUTCOMES results. Further studies in this high-risk population are needed to demonstrate the hypothesis raised by our results,” investigators added.1