P306 - HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA IN CANADA: 2025 REGISTRY UPDATE

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare autosomal recessive disorder of lipid metabolism, marked by elevated LDL-C levels and an increased risk of premature cardiovascular disease. The Canadian HoFH Registry was established in 2008 as part of the Familial Hypercholesterolemia (FH) Canada network by clinicians to better understand the disease burden, treatment approaches, and clinical outcomes in this population. The registry identifies and follows patients with available individual-level data across five provinces: Quebec, Ontario, British Columbia, Alberta, and Nova Scotia.
This study aimed to provide an updated overview of the Canadian HoFH Registry, highlighting its expansion as well as current clinical characteristics, new lipid lowering therapies (LLTs), and longitudinal cardiovascular outcomes in this cohort.

METHODS AND RESULTS: The study used an observational study design. A standardized questionnaire was sent to FH Canada network sites to collect updated information on recent lipid profiles, lipid lowering therapies and recent cardiovascular profiles as well as to enrol new participants. Patients were eligible for inclusion in the Canadian HoFH registry if they had received a clinical or genetic diagnosis of HoFH by the treating physician. Data collection occurred between January 2024 – March 2025. Participant demographic, clinical and lipid characteristics, LLTs and cardiovascular events will be presented using standard descriptive statistics, including median and interquartile range (IQR), and frequency with percentage. Data were available on a total of 63 patients. At last follow-up visit, median age was 45 years (IQR: 30-61 years). The median age at diagnosis was 14 years (IQR: 6-31) and the median highest recorded LDL-C levels was 13 mmol/L (IQR: 10.6-16.3 mmol/L). Lowest treated LDL-C levels were 3.0 (IQR: 2.1 – 4.9 mmol/L) with 82.5% of patients on statins, 81% on ezetimibe, 42.9% on proprotein convertase subtilisin/kexin type 9 inhibitors, 19% on lomitapide, 36.5% on evinacumab, and 41.3% treated with low-density lipoprotein apheresis or plasmapheresis. Major adverse cardiovascular events were observed in 22% of patients with the average onset at 41 years (IQR: 23-50 years).

Conclusion: This updated analysis of the Canadian HoFH Registry offers insights into the evolving lipid-lowering strategies, and cardiovascular outcomes of patients with HoFH in Canada. One notable finding is the rapid uptake of new therapies, such as inhibitors of ANGPTL3. Despite advances in treatment, a significant proportion of patients continue to experience major cardiovascular events, underscoring the need for earlier diagnosis, aggressive lipid management, and continued access to novel therapies to optimize long-term outcomes in this population.