In patients with moderate hypertriglyceridemia, significant reductions in triglyceride and remnant cholesterol levels with olezarsen, on top of standard-of-care lipid-lowering therapy, did not translate into a significant change from baseline in noncalcified coronary plaque volume (NCPV), according to results from Essence-CTA, a substudy of the Essence-TIMI 73b trial, presented during a Late-Breaking Clinical Trial session at ACC.26 in New Orleans and simultaneously published in Circulation.

The main results of Essence-TIMI 73b showed that olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III (ApoC3), compared with placebo, significantly reduced triglycerides in patients with triglyceride levels ≥150 mg/dL, measurable plaque on baseline coronary computer tomographic angiography (CCTA) and either a high risk or known presence of atherosclerosis.

At 12 months, 468 patients had a follow-up CCTA and comprise the imaging substudy population. Of these patients, 349 were treated with olezarsen and 119 with placebo. Their median age was 63 years and a third were women; 97% were on baseline lipid-lowering therapy, 43% had known coronary artery disease and 57% had diabetes.

The effect of olezarsen compared with placebo was similar with the main results, with a 64% reduction in triglycerides at six months, remnant cholesterol by 72% and apolipoprotein B by 16%, while there was no difference in LDL-C.

In this imaging cohort, the median baseline NCPV was 130.7 mm³ in the treatment arm and 122.7 mm³ in the placebo arm.

At 12 months, for the primary endpoint of percent change in NCPV from baseline, there was no between-group difference, with a placebo-adjusted least-squares mean difference of 2.98% (p=0.36). The median percent change in NCPV was –3.91% with placebo and –5.35% with olezarsen.

Additionally, there were no differences between groups for the secondary endpoints of low-attenuation, calcified or total plaque volumes. The researchers note that the neutral effect of olezarsen was consistent across subgroups.

Investigators call for additional research into the possible effects of olezarsen. “Ultimately, a cardiovascular outcomes trial would need to be performed to determine the cardiovascular benefit of long-term ApoC3 inhibition, tested either as a monotherapy or in combination with another lipid-lowering therapy,” said Nicholas Marston, MD, the study’s lead author.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Atherosclerotic Disease (CAD/PAD), Hypertriglyceridemia, Lipid Metabolism

Keywords: ACC Annual Scientific Session, ACC26, New Orleans, Coronary Artery Disease, Triglycerides, Hypertriglyceridemia, Lipid Lowering