Inclisiran superior to ezetimibe in LDL-C reduction in patients without ASCVD

Treatment with inclisiran monotherapy demonstrates good tolerability and better reduction in low-density lipoprotein cholesterol (LDL-C) levels when compared with ezetimibe and placebo in patients without atherosclerotic cardiovascular disease (ASCVD), reports a study.

A total of 350 participants (mean age 46.1 years, mean baseline LDL-C level 135.4 mg/dL, mean BMI 29.8 kg/m²) were included in this study. Of these, 62.6 percent were female, 10.6 percent were Black, and 39.7 percent were Hispanic or Latino.

Participants were randomly allocated to treatment with inclisiran (n=174), ezetimibe (n=89), or placebo (n=87). The median predicted ASCVD risk score at 10 years was 2.2 percent.

At day 150, the mean percentage change in LDL-C from baseline was ‒46.5 percent for inclisiran, ‒11.2 percent for ezetimibe, and 1.4 percent for placebo. The differences were ‒47.9 percent with inclisiran vs placebo and ‒35.4 percent with inclisiran vs ezetimibe (p<0.0001 for both).

In addition, the use of inclisiran resulted in favourable improvement in other lipid and lipoprotein(a) levels. It also was well-tolerated and had no new safety concerns.

“Inclisiran as monotherapy is superior to both placebo and ezetimibe in reducing LDL-C levels over a 6-month follow-up period and was well-tolerated,” the investigators said. “These findings are consistent with prior observations in statin-treated patients.”

This randomized, double-blind, multicentre, placebo- and active-comparator controlled phase III trial involved adults (aged 18‒75 years) without prior ASCVD, diabetes, or familiar hypercholesterolemia, with a fasting LDL-C ≥100 to <190 mg/dL and 10-year predicted ASCVD risk of <7.5 percent by pooled cohort equation. Participants were also not receiving any lipid-lowering therapy.