Data from single-arm clinical trials show that the combination of high-intensity statin therapy and alirocumab was effective in patients with familial hypercholesterolemia (FH) with high baseline plaque burden or with larger unstable cores. This suggests that it may result in a greater regression of plaque burden in patients with blood clots. These findings show that Circulation: Cardiovascular Imaging.

Results from the ARCHITECT (Effect of alirocumab on atherosclerotic plaque volume, structure and composition, ClinicalTrials.gov ID: NCT05465278) study show that alirocumab treatment reduces plaque burden and improves coronary atherosclerotic characteristics in patients with FH. It was shown that

This analysis evaluated atherosclerotic plaque characteristics associated with greater outcomes with alirocumab. The ARCHITECT study was a Phase IV, open-label, multicenter study in FH patients (N=104) without clinical atherosclerotic cardiovascular disease between 2018 and 2019. received alirocumab 150 mg subcutaneously every 14 days for 78 weeks. Maximum tolerated stable dose of statin with or without ezetimibe. Changes in plaque burden were assessed using computed tomography angiography at baseline and at his 78th week.

The study population consisted of 51.9% women, median age 53.3 years (IQR, 46.2-59.4), BMI 27.8 (IQR, 24.3-31.2), and 92.3% receiving high-potency, high-dose statins. was receiving. They had taken statins for 18.6 (IQR, 9.6 to 26.6) years, 85.6% had taken ezetimibe, and had been taking ezetimibe for 8.6 (IQR, 1.8 to 13.6) years.

Overall coronary plaque burden decreased from 34.6% at baseline to 30.4% at follow-up, 4.6% (95% CI, -7.7% to -1.9%; P <.001) decreases. At the patient level, 87.5% showed regression of coronary plaque burden.

When stratified by plaque component, a significant improvement was observed in total plaque volume from baseline to follow-up (mean difference) [MD]-133.4 mm³; P <.001), fibrotic plaque (MD, -67.0 mm)³; P <.001), fibrofatty plaque (MD, -28.1 mm)³; P <.001), necrotic plaque (MD, -18.5 mm)³; P <.001), unstable core (MD, -47.6 mm)³; P <.001) volume. However, a non-significant increase in calcified plaque was observed (MD, 0.03 mm)³; P =.95).

In univariate analysis, regression of plaque burden was associated with total plaque burden, necrotic plaque, fibrofatty plaque, unstable core, and BMI, whereas progression of plaque burden was associated with fibrotic plaque.

In multivariate linear regression analysis, regression of plaque burden was associated with unstable core (b, 0.15%; 95% CI, 0.08%-0.22%; P <.001) and total plaque burden (b, 0.36%; 95% CI, 0.13%-0.59%; P =.002 at baseline) and tended to be associated with BMI (b, 0.03; 95% CI, -0.004 to 0.06; P =.09).

Limitations of this study include its nonrandomized, open-label design and lack of a comparison group.

“These findings demonstrate how treatment with alirocumab in addition to high-intensity statin therapy may produce greater PB.” [plaque burden] “Regression is seen in FH patients with high baseline PB and in patients with high fibrofatty and necrotic components (unstable core),” the study authors wrote.

Disclosure: Some study authors declared affiliations with biotechnology, pharmaceutical, and/or device companies. Please refer to the original reference material for a complete list of disclosures.