Essence‑CTA: Does Olezarsen Reduce Noncalcified Coronary Plaque Volume?

In patients with moderate hypertriglyceridemia, the antisense oligonucleotide olezarsen—given on top of standard‑of‑care lipid‑lowering therapy—produced substantial drops in triglycerides and remnant cholesterol, but did not significantly change noncalcified coronary plaque volume (NCPV), according to the Essence‑CTA imaging substudy of Essence‑TIMI 73b, presented at ACC.26 and published in Circulation.

The substudy analyzed 468 patients (median age 63, one‑third women) with serial coronary CT angiography (CCTA) over 12 months, of whom 349 received olezarsen and 119 received placebo; nearly all were on guideline‑directed lipid‑lowering therapy, with about 43% having known coronary artery disease and 57% diabetes. 

Olezarsen cut triglycerides by 64%, remnant cholesterol by 72%, and apolipoprotein B by 16% at 6 months, with no effect on LDL‑C.

Despite these profound lipid‑profile changes, there was no significant difference in the percent change in NCPV: the placebo‑adjusted least‑squares mean difference was +2.98% (p = 0.36), with median reductions of −3.91% (placebo) versus −5.35% (olezarsen). 

There were no differences in low‑attenuation plaque, calcified plaque, or total plaque volume, and the neutral effect of olezarsen was consistent across patient subgroups.

The lead investigator underscores that Essence‑CTA does not rule out clinical benefit; instead, it underscores the need for a large cardiovascular outcomes trial to test whether long‑term ApoC3 inhibition with olezarsen, alone or added to other lipid‑lowering regimens, reduces MI, stroke, or cardiovascular death, even if CCTA‑measured coronary plaque volume shifts only modestly.