Physicians' Academy for Cardiovascular Education

ApoC-III inhibition reduces triglycerides in patients at high risk for or with established ASCVD

Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk

Literature - Tardif JC, Karwatowska-Prokopczuk E, St Amour E et al. - Eur Heart J. 2022 Jan 13;ehab820. doi: 10.1093/eurheartj/ehab820.

Introduction and methods


Apolipoprotein C-III (apoC-III) is an important regulator of plasma triglyceride levels [1,2]. A study suggested that ApoC-III may exert proatherogenic effects, both directly by enhancing inflammation in the vessel wall or indirectly by fostering hypertriglyceridemia [3]. In addition, epidemiological studies have shown that apoC-III levels are associated with ASCVD risk and CV mortality [4-6].

Olezarsen is an N-acetyl-galactosamine (GalNAc)-conjugated, antisense oligonucleotide targeted to hepatic APOC3 mRNA. Olezarsen can thereby inhibit apoC-III production.

Aim of the study

This study evaluated the effect of apoC-III inhibition by olezarsen on triglyceride levels and triglyceride-rich lipoprotein (TRL) levels in patients with elevated fasting triglyceride levels (200-500 mg/dl or 2.26-5.65 mmol/L) who are at high risk for ASCVD or with established ASCVD.


This phase 2, dose-ranging, multi-center, randomized, double-blind, placebo-controlled trial randomized 141 patients to one of four treatment groups (olezarsen 10 mg or placebo subcutaneously every 4 weeks; olezarsen 15mg or placebo subcutaneously every 2 weeks, olezarsen 10mg or placebo subcutaneously every week, and olezarsen 50mg or placebo subcutaneously every 4 weeks). In each treatment group, patients were randomized in a 4:1 ratio to receive olezarsen or placebo. Patients received treatment for at least 6 months and up to 12 months. Post-treatment follow-up period was 13 weeks.


The primary efficacy endpoint was the percent change in fasting triglyceride levels from baseline to 6 months of treatment. Secondary endpoints included the percent change from baseline to 6 months of treatment in apoC-III, total cholesterol, LDL-c, HDL-c, non-HDL-c, VLDL-c, apoB, and apoA-I, and the proportion of patients who achieved serum triglyceride levels < 150 mg/dL (<1.7mmol/L) or triglyceride levels <100 mg/dL (<1.13 mmol/L).

Main results

Changes in triglyceride levels

Changes in atherogenic lipids and apolipoproteins levels

Proportion of patients achieving triglyceride levels<150 mg/dL or <100 mg/dL



This phase 2 study shows that targeting hepatic APOC3 mRNA with olezarsen in patients at risk of or with established ASCVD results in substantial reductions in fasting triglyceride levels, compared with placebo.


Show references

Find this article online at Eur Heart J.

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