Endocrine Abstracts

Background: PCSK9 inhibitors offer potent LDL-cholesterol (LDL-C) reduction in patients with severe or familial hypercholesterolaemia (FH), yet long-term real-world data on lipid outcomes and treatment persistence remain limited in UK secondary care, where pathway variation and resource constraints often influence adherence.

Methods: This single-centre evaluation in a secondary care lipid clinic included adults initiated on PCSK9i therapy between 2017 and 2024, retrospectively evaluated using Cerner prescribing and laboratory records. Patients with ≥12 months of follow-up were included; lipid parameters were assessed at baseline and annually for up to seven years. Primary outcomes were changes in LDL-C and non-HDL-C; the secondary outcome was treatment persistence.

Results: Fifty-three patients (mean age 53 ± 12 years) were included: 44 received alirocumab and 9 evolocumab. Twenty-one patients had genetically or clinically confirmed heterozygous FH, and 21 patients were treated for primary prevention. Baseline mean LDL-C was 5.0 ± 1.2 mmol/l, declining to 3.0 ± 0.8 mmol/l at year 1 (−39 %) and remaining stable between 2.2–2.8 mmol/l (−43 to −56 %) over seven years. Non-HDL-C decreased from 6.4 ± 1.5 to 3.4–4.1 mmol/l (−36 to −46 %). Treatment persistence declined progressively: for alirocumab, 59 % remained on therapy at year 3, 37 % at year 5, and 27 % at year 7. For evolocumab, persistence was higher initially (100 % at year 5) but 11 % discontinued by year 7. Reasons for discontinuation in both groups were not documented and should be investigated further.

Conclusion: In this seven-year real-world evaluation, PCSK9i therapy achieved durable lipid reductions consistent with clinical-trial efficacy. However, long-term persistence was suboptimal, particularly for alirocumab. These findings highlight that, beyond efficacy, adherence represents the key challenge in delivering sustained lipid optimisation within NHS practice.