Endocrine Abstracts

Background: Inclisiran is the first clinically available small interfering RNA (siRNA)-based treatment, has been shown to reduce pro-atherogenic lipoproteins in patients with or without familial hypercholesterolemia (FH), diabetes mellitus (DM), or atherosclerotic cardiovascular disease (ASCVD), but has not been evaluated in Middle Eastern populations.

Methods: Retrospective review of patients initiating inclisiran treatment for any indication at our centre between 2021 and 2022. All individuals followed up for at least 90 days or with at least one lipid panel post-initiation were included. Participants subclassified into DLCN-diagnosed FH (n = 36) and non-FH (n = 56) groups.

Results: Inclisiran was initiated in 92 individuals, mean ± sd age 54.7 ± 11.6 years, 48 (52.2%) males, 70 (76.1%) with secondary prevention (prior history of ASCVD event), 66.7% with DM and 25 (27.2%) with statin intolerance. At 90 days, substantial reductions in serum Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and total cholesterol:HDL-C (TC:HDL-C) were observed in both primary and secondary prevention, and FH and non-FH individuals: FH; median (IQR) reduction in LDL-C was 61.4% (51.2%; 84.8%), TG 25% (7.5%; 45%), TC:HDL-C 42.2% (30.7%; 60.7%), non-FH; LDL-C 33.1% (3.2%; 59.4%), TG 13.5% (-14%; 32.1%), TC:HDL-C 22.9% (0.4%; 40.5%), all P-values < 0.0001. American College of Cardiology / American Heart Association (ACCA/AHA) LDL-C targets were consistently achieved in 68 (73.9%) patients during a follow-up of 107 (27-237) days. Non-attainment of LDL-C target was attributed to non-adherence in 13 (54.2%), and discontinuation of treatment in 5 (20.8%) patients. New ASCVD hazard adjusted for age, sex, smoking status, diabetes, and FH was 0.66, P<0.05 in ACC/AHA LDL-C target achievers against non-achievers.

Conclusions: Clinically meaningful and sustained reductions in LDL-C, TG, and cholesterol ratios were observed after inclisiran initiation. Inclisiran is safe and effective in the management of hyperlipidemia and ASCVD in a predominantly Arabic population.