Endocrine Abstracts

Background: Elevated low-density lipoprotein cholesterol (LDL-C), which arises due to genetic and environmental factors, has a causal role in the pathogenesis of cardiovascular disease (CVD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are approved for patients with familial hypercholesterolaemia (FH) and patients at high risk of CVD due to non-familial hypercholesterolaemia (non-FH). In clinical trials, PCSK9 inhibitors are well-tolerated and lead to reductions in LDL-C of up to 67%. However, evidence regarding the efficacy and tolerability of the drug in real-world clinical practice remains scarce.

Aims: This study aimed to evaluate the tolerability and efficacy of PCSK9 inhibitor therapy at a tertiary centre lipid clinic. Subanalyses were performed to determine whether outcomes differ between patient subpopulations.

Methods: This was a retrospective study involving patients who commenced PCSK9 inhibitor therapy at Imperial College Healthcare Trust lipid clinic, between 1^st January 2017 and 31^st December 2019. Demographics, clinical characteristics and laboratory results were collected at the time of PCSK9 initiation, and after 3, 6, 12 and 24 months, where applicable. Outcome measures included mean and percentage change in LDL-C over time.

Results: 37 patients were analysed after exclusions, of which 30 patients had FH, and 7 patients had non-FH. Within the whole cohort, there was a significant reduction in mean LDL-C of 34% within 3 months (P < 0.001), which was sustained for at least 2 years. There was a non-significant difference in responsiveness to therapy between FH and non-FH groups, and at 12 months, there was regression of LDL-C to above baseline in the non-FH group.

Conclusion: PCSK9 inhibitor therapy was well-tolerated and produced significant reductions in LDL-C within 3 months in this patient cohort. Reasons for divergent responses between FH and non-FH groups require further exploration.