This CCTA sub-study of Essence-TIMI 73b showed that olezarsen — an APOC3 antisense oligonucleotide — lowered triglycerides by ~60% and remnant cholesterol by ~70%, with neutral LDL-C and ~15% apoB reduction. Over 12 months in patients with moderate hypertriglyceridemia and non-calcified coronary plaque, olezarsen produced a placebo-adjusted reduction in non-calcified plaque volume. It provides some of the first imaging evidence that triglyceride-directed therapy favorably modifies coronary atherosclerosis.
Background: Whether lowering triglyceride-rich lipoproteins and remnant cholesterol favorably modifies coronary atherosclerosis is unclear. Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III, reduces triglycerides by ~60% and remnant cholesterol by ~70%, has a neutral effect on LDL cholesterol (LDL-C), and reduces apolipoprotein B (apoB) by ~15% in moderate hypertriglyceridemia. We investigated the effect of olezarsen on coronary plaque in adults with largely moderate hypertriglyceridemia.Methods: We conducted a coronary computed tomography angiography (CCTA) study within Essence-TIMI 73b, a randomized, placebo-controlled trial of olezarsen vs. placebo that enrolled patients between November 2022 and February 2024. Inclusion criteria were triglycerides ≥150 mg/dL (2.26 mmol/L), presence or high risk for cardiovascular disease, and non-calcified plaque on baseline CCTA. The primary endpoint was percent change from baseline to 12 months in non-calcified plaque volu
