Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients with Homozygous Familial Hypercholesterolemia: Study Protocol of the LILITH Study

Abstract

Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, leading to premature and severe cardiovascular disease. Lomitapide, an inhibitor of microsomal triglyceride transfer protein (MTP), effectively lowers LDL-C in HoFH patients. However, data on its impact on major adverse cardiovascular events (MACE) remain limited, and randomized controlled trials are not feasible due to the rarity of the condition and ethical constraints. This article presents the protocol of the LILITH study (Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events in Patients with Homozygous Familial Hypercholesterolemia), a multicenter, observational, retrospective–prospective cohort study. The study aims to compare the incidence of MACE during the first three years of lomitapide treatment with that observed in the three years preceding treatment, within the same cohort of adult HoFH patients (target N=72). Clinical data, including MACE, lipid levels, liver function, safety outcomes, and concomitant lipid-lowering therapies, will be collected. The primary analysis will apply McNemar’s test to assess changes in MACE incidence pre- and post-treatment. This methodological approach enables the evaluation of long-term cardiovascular outcomes in a real-world setting for a rare disease population.