LAUSR

Homozygous familial hypercholesterolaemia (HoFH) is characterised by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and results from multiple mutations in genes affecting the LDL receptor pathway. Patients are at risk of premature atherosclerotic cardiovascular disease (ASCVD) and premature death. Lomitapide is a microsomal triglyceride transfer protein inhibitor developed to treat HoFH, but cardiovascular outcome data are lacking. We evaluated detailed data from five HoFH patients and one patient with heterozygous FH (HeFH) and a very severe phenotype. We also analysed confirmatory data from a further 8 HoFH cases. In total, we analysed data from patients in seven global centres in six countries who were all treated with lomitapide with long-term follow-up. Carotid intima-media thickness (CIMT) imaging was recorded on an ad hoc basis to monitor ASCVD in HoFH. Lomitapide resulted in marked decreases in LDL-C of 56.8–93.9% [77.7–93.9% in the 6 initial cases (mean nadir 64.8 ± 30.1 mg/dL); 56.8–86.0% in the 8 confirmatory cases (mean nadir 131.4 ± 38.2 mg/dL)]. CIMT regressed in 50% of cases (mean follow-up 5.0 ± 3.1 years in initial six cases, and 4.4 ± 1.4 years in confirmatory cases). In the remaining patients, CIMT showed little further change. In patients where assessments of plaque area were available, regression or stabilisation in CIMT was accompanied by clinically significant regression of plaque area. Lomitapide reduces LDL-C levels in patients with HoFH and severe LDL-C phenotypes, and results in stabilisation and/or regression of CIMT, which is an established marker of ASCVD risk. Additional data are needed to determine if this confers a survival benefit in these very high-risk patients.