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Alirocumab, Familial Hypercholesterolemia, and Atherosclerosis Regression
Quick Takes
- In patients with familial hypercholesterolemia (FH) without previous clinical ASCVD on statin treatment with or without ezetimibe, the PCSK9 inhibitor alirocumab resulted in a significant regression of the coronary atherosclerotic burden.
- The study findings show a mechanistic explanation that could link atherosclerotic plaques and clinical outcomes.
- Regression and stabilization of atherosclerotic plaque might reduce clinical events in patients with FH, but needs further prospective study.
Study Questions:
What are the changes in coronary plaque burden and its characteristics after treatment with alirocumab in asymptomatic subjects with familial hypercholesterolemia (FH) receiving treatment with maximum tolerated statin dose with or without ezetimibe?
Methods:
The ARCHITECT investigators conducted 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 FH without clinical atherosclerotic cardiovascular disease (ASCVD). Participants underwent an initial coronary computed tomographic angiography (CCTA) at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneously every 14 days in addition to high-intensity statin therapy. The main outcome was the change of coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree based on analysis of CCTA. A multivariate forward linear regression analysis was conducted to determine whether low-density lipoprotein cholesterol (LDL-C) decrease was associated with plaque burden regression.
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 LDL-C 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:
The authors report that treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on CCTA in patients with FH without clinical ASCVD.
Perspective:
This study reports that in patients with FH without previous clinical ASCVD on statin treatment with or without ezetimibe, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab resulted in a significant regression of the coronary atherosclerotic burden. Of note, the current study analyzed plaque burden in the complete coronary artery tree and not only in a segment, as in previous studies. Furthermore, the study findings show a mechanistic explanation that could link atherosclerotic plaques and clinical outcomes. Regression and stabilization of atherosclerotic plaque might reduce clinical events in patients with FH, but needs further prospective study.
Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Nuclear Imaging
Keywords: Angiography, Atherosclerosis, Cholesterol, LDL, Computed Tomography Angiography, Coronary Angiography, Coronary Artery Disease, Diagnostic Imaging, Dyslipidemias, Ezetimibe, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hyperlipoproteinemia Type II, PCSK9 protein, human, Plaque, Atherosclerotic, Primary Prevention, Proprotein Convertase 9, Vascular Diseases
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