ESSENCE-TIMI 73b
Effect of Olezarsen on Noncalcified Coronary Plaque Volume: The ESSENCE-TIMI 73b Coronary CTA Substudy
Presented by Nicholas Marston — Brigham and Women's Hospital
Subspecialty: Lipid / Prevention
Published in Circulation
Key Result
Despite dramatic triglyceride reduction (60-64%), olezarsen did NOT reduce noncalcified coronary plaque volume vs placebo at 12 months (p=0.36). Neutral imaging results despite robust lipid changes.
What did this trial find?
The ESSENCE-TIMI 73b coronary CTA substudy found that despite 60-64% triglyceride reduction and 72% remnant cholesterol reduction with olezarsen, there was no significant change in noncalcified coronary plaque volume at 12 months (p=0.36). This neutral imaging result raises important questions about whether triglyceride lowering alone translates to atherosclerosis regression and whether cardiovascular outcomes trials are needed to determine the benefit of ApoC3 inhibition. The parent trial showed robust triglyceride lowering (58-61% placebo-adjusted at 6 months), generating meaningful debate about the disconnect between lipid changes and plaque effects.
Why does this trial matter?
Meaningful interpretation debate. The CTA substudy's neutral plaque result despite dramatic triglyceride lowering creates a genuine disconnect between biomarker efficacy and atherosclerosis imaging — raising real questions about whether triglyceride lowering alone benefits CV outcomes. However, external commentary is limited; most available quotes come from the study authors themselves, with the only named outside commentator being the ESC discussant Nordestgaard whose full quote was truncated in the source material.
Study Design
Randomized, double-blind, placebo-controlled imaging substudy (N=468)
Clinical Implications
Effective triglyceride lowering with olezarsen does not translate into measurable coronary plaque regression at 12 months. Raises questions about the plaque-modifying potential of triglyceride-lowering strategies alone.
Abstract
The ESSENCE-CTA substudy of the ESSENCE-TIMI 73b trial included 468 patients with triglycerides >=150 mg/dL and measurable coronary plaque who underwent repeat coronary CTA at 12 months. Patients were randomized to olezarsen (targeting apolipoprotein C-III) at 50 or 80 mg or placebo. Despite 60-64% triglyceride reduction, 72% remnant cholesterol reduction, and 15-16% apoB reduction, olezarsen did not significantly reduce noncalcified coronary plaque volume vs placebo (least-squares mean difference 2.98%, p=0.36). No differences in low-attenuation, calcified, or total plaque volumes were observed.