J Am Coll Cardiol

Inclisiran monotherapy yields robust LDL-C reduction in primary prevention

July 8, 2025

Inclisiran monotherapy is superior to both ezetimibe and placebo for LDL-C lowering in a primary prevention population not receiving other lipid-lowering therapy, with a favorable safety profile.

Study details: The randomized, double-blind, multicenter phase 3 VICTORION-Mono trial (NCT05763875) evaluated inclisiran monotherapy vs. ezetimibe and placebo in 350 adults aged 18 to 75 years without ASCVD, diabetes, or familial hypercholesterolemia. Participants had a baseline LDL-C of 100–190 mg/dL and 10-year ASCVD risk <7.5% and were not on any lipid-lowering therapy. Randomization was 2:1:1 to inclisiran (initial and 3-month doses), ezetimibe, or placebo. Primary endpoint was percent change in LDL-C at day 150; safety was also assessed.

Results: Inclisiran reduced LDL-C by 46.5% from baseline at day 150, vs. -11.2% with ezetimibe and +1.4% with placebo. The placebo-corrected difference was -47.9% (p<0.0001), and vs. ezetimibe was -35.4% (p<0.0001). Improvements were also seen in other lipid parameters, including lipoprotein(a). Inclisiran was well tolerated, with no new safety signals.

Source:

Taub PR, et al. (2025, May 5). J Am Coll Cardiol. Safety and Lipid-Lowering Efficacy of Inclisiran Monotherapy in Patients Without ASCVD: The VICTORION-Mono Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40392667/