Impact of Evinacumab on coronary plaques in patients with Homozygous Familial Hypercholesterolemia: Protocol of the "EVOLVE-HoFH" study (EValuation of atherOma pLaque Volume after Evinacumab in HOmozygous Familial Hypercholesterolemia)
Makaleler > Tam Makale · 2025
Yazarlar: Willemijn A.M. Schonck, Chiara Crosti, Aurora Marchesin, Antonio Gallo, Latife Meral KAYIKÇIOĞLU, Maciej Banach, Marina Cuchel, Richard Jones, Pinay Kainth, Alberico L. Catapano, Erik S.G. Stroes
European Atherosclerosis Journal, Uluslararası, 2025, cilt 4, ss 75-79
Özet
Background: Homozygous Familial Hypercholesterolemia (HoFH) is a rare and severe genetic disorder characterized by markedly elevated low-density lipoprotein-cholesterol (LDL-C) levels from birth onwards, leading to accelerated and premature atherosclerotic cardiovascular disease (ASCVD). Evinacumab, a monoclonal antibody targeting angiopoietin-like protein 3 (ANGPTL3), has been shown to effectively reduce LDL-C in this population. However, its direct impact on coronary atherosclerotic plaque burden remains to be established. Given the rarity of the condition, randomized placebo-controlled clinical trials on major adverse cardiovascular events (MACE) are unfeasible. Aim and Methods: This document describes the methodology of the EVOLVE-HoFH study, a real-world, observational, multicenter, international study (prospective and retrospective) designed to assess whether intensification of lipid-lowering therapy (LLT) with Evinacumab leads to regression or stabilization of the coronary atherosclerotic plaque burden as well as altered composition in patients with HoFH. The study will use Coronary Computed Tomography Angiography (CCTA), a validated surrogate risk marker, to compare changes in plaque volume in a group of patients initiating treatment with Evinacumab ("intensified treatment group") with a "conventional treatment comparator group." The primary endpoint is the difference in change in percent non-calcified plaque volume (%NCPV), a key indicator of plaque instability, between baseline and 18-24 months follow-up. Conclusion: This pragmatic methodological approach is designed to overcome the barriers of research in rare diseases, allowing for the evaluation of a clinically relevant and mechanistically informative surrogate efficacy endpoint. The results will provide the first evidence of the beneficial impact of Evinacumab on coronary atherosclerosis, filling an important knowledge gap.