Endocrine Abstracts

Purpose: Inclisiran is the first small interfering RNA (siRNA)-based treatment approved to reduce pro-atherogenic lipoproteins in patients with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of low-density lipoprotein cholesterol (LDL-C). We report, to the best of our knowledge, the first evaluation of its effects in a Middle Eastern population.

Methods: Retrospective review of patients initiating inclisiran treatment at an outpatient Diabetology/Endocrinology and Cardiology Centre between May 2021 and December 2022. All individuals followed up for ≥90 days or with at least one lipid determination post-initiation were included. Participants were categorized into primary (n=57) and secondary prevention (n=89) groups according to previous ASCVD.

Results: Inclisiran was initiated in 146 individuals, mean±S.D. age 54.8±12.12 years, 82 (56.2%) males, 28 (19.2%) with FH diagnosis, 89 (61%) with Diabetes Mellitus (DM) and 35 (23.9%) with statin intolerance. Median follow-up was 137 (90–193) days. At 90 days, median (IQR) reductions in serum LDL-cholesterol (LDL-C), and triglycerides were respectively −37.9% (−9.5%; −51.2%), −12.0% (−9.8%; −40.5%) in primary prevention, and −54.1% (−17.1%; −71.4%), and −15.3% (−14%; −38.8%) in secondary prevention (all P-values < 0.001). LDL-C goals were attained in 110 (75.3%) patients. Non-attainment of LDL-C goal was attributed to system effect in 26 (72.2%), biological effect in 5 (13.9%), and discontinuation of treatment in 5 (13.9%) patients. Therapy was well tolerated.

Conclusion: To the best of our knowledge, this current study is the first from the Middle East and North Africa (MENA) region that reports the real-world efficacy and safety of inclisiran in a mixed-risk population of individuals with HeFH and other non-FH indications. Clinically meaningful and sustained reductions in pro-atherogenic lipids with good tolerability were observed after inclisiran initiation.

Keywords: Inclisiran, small interfering RNA (siRNA), Familial hypercholesterolemia, Atherosclerotic cardiovascular disease, Low-density lipoprotein cholesterol, Diabetes Mellitus, PCSK9-inhibitor.