Ezetimibe in the management of homozygous familial hypercholesterolaemia.

Background: Homozygous familial hypercholesterolaemia (HoFH) is a severe lipid disorder leading to accelerated atherosclerotic cardiovascular disease (ASCVD). This study aimed to evaluate the efficacy of ezetimibe, a cholesterol absorption inhibitor, in reducing low-density lipoprotein cholesterol (LDL-C) levels in patients with genetically confirmed HoFH.

Methods: This retrospective review included 48 individuals with genetically confirmed HoFH attending the Lipid Clinic at an Academic Hospital in Johannesburg, South Africa. All patients were on stable high-intensity statin therapy for at least 6 months before starting ezetimibe 10 mg orally daily. Lipid profiles at baseline and after 3 and 6 months of ezetimibe therapy were documented. Responders (LDL-C reduction ≥20%) were compared to nonresponders (LDL-C reduction <20%).

Results: Ezetimibe led to a 19.1% further reduction in LDL-C at 6 months. Among the participants, 23 were considered responders and 25 were nonresponders. Responders showed a 26.4% LDL-C reduction at 3 months and 31.6% at 6 months, compared to nonresponders with 8.5% and 5.9% reductions in LDL-C respectively. Individuals with the null LDL receptor variant c.1285G>A (p.Val429Met) were less likely to respond. However, response to ezetimibe was highly variable across all pathogenic variants.

Conclusion: Ezetimibe, in combination with high-intensity statin therapy, significantly reduces LDL-C levels in patients with genotypically confirmed HoFH. However, the response to ezetimibe is highly variable and unpredictable across genotypes. This study supports the inclusion of ezetimibe in the treatment regimen for all HoFH patients to reduce the risk of ASCVD. Further studies are needed to understand the variable responses to ezetimibe among different genotypes and in HoFH individuals with the same genotype.