Safety and Lipid-Lowering Efficacy of Inclisiran Monotherapy in Patients Without ASCVD

Abstract

Background Inclisiran administration twice-yearly (after initial and 3-month doses) effectively reduces low-density lipoprotein cholesterol (LDL-C) in patients on maximally tolerated statins with atherosclerotic cardiovascular disease (ASCVD), risk equivalents, or heterozygous familial hypercholesterolemia. Objectives In this study, the authors sought to evaluate whether inclisiran is superior as monotherapy over placebo and ezetimibe in reducing LDL-C in a primary prevention population without ASCVD. Methods VICTORION-Mono (V-Mono), a 6-month, randomized, double-blind, multicenter, placebo- and active-comparator controlled phase 3 trial, assessed inclisiran monotherapy in adult participants (aged 18-75 years) without prior ASCVD, diabetes, or familial hypercholesterolemia, with a fasting LDL-C of 100-190 mg/dL and 10-year predicted ASCVD risk of Results Overall, 350 participants were randomized (n = 174, 89, and 87 to inclisiran, ezetimibe, or placebo, respectively) and received the assigned treatments. The study included a diverse population: 62.6% of participants were female, 10.6% were Black or African American, and 39.7% were Hispanic/Latino. Mean participant age was 46.1 years, mean baseline LDL-C level was 135.4 mg/dL, mean body mass index was 29.8 kg/m 2 , and median 10-year predicted ASCVD risk score was 2.2%. The mean percentage change in LDL-C from baseline at day 150 for placebo was 1.4%, for ezetimibe -11.2%, and inclisiran -46.5%. The difference in the change fr…