Does olezarsen reduce plaque volume in adults with moderate hypertriglyceridemia?

Olezarsen is a medication that lowers triglycerides by targeting apolipoprotein C-III. In adults with moderate hypertriglyceridemia (triglycerides 150-499 mg/dL), a 12-month imaging study found that olezarsen did not significantly reduce noncalcified plaque volume compared to placebo, even though it lowered triglycerides by about 60% and remnant cholesterol by about 70% ²⁶. This suggests that lowering triglycerides alone may not be enough to shrink coronary plaque in the short term.

What the research says

The Essence-TIMI 73b trial included a coronary computed tomography angiography (CTA) substudy that measured changes in noncalcified plaque volume over 12 months ²⁶. Among 468 participants (349 on olezarsen, 119 on placebo), the primary endpoint—percent change in noncalcified plaque volume—showed no significant difference between the olezarsen and placebo groups ²⁶. This result occurred despite olezarsen reducing triglycerides by ~60% and remnant cholesterol by ~70%, with a neutral effect on LDL cholesterol and a ~15% reduction in apolipoprotein B ²⁶. The study enrolled adults with moderate hypertriglyceridemia (median baseline triglycerides 249 mg/dL) and high cardiovascular risk; 97% were already on lipid-lowering therapy ²⁶. The findings indicate that while olezarsen effectively lowers triglyceride-rich lipoproteins, this did not translate into measurable plaque regression over one year ²⁶. Other sources confirm that olezarsen can lower triglycerides by 40-70% in various settings ³, but the plaque imaging data specifically address the question of coronary atherosclerosis. A separate trial of a similar drug, plozasiran, showed reduced pancreatitis risk in severe hypertriglyceridemia ⁴, but that does not directly address plaque volume in moderate hypertriglyceridemia.

What to ask your doctor

• What does the lack of plaque reduction with olezarsen mean for my heart disease risk?
• Are there other treatments that have been shown to reduce plaque volume?
• Should I consider lifestyle changes, like a Mediterranean diet and physical activity, which have been shown to lower post-meal triglycerides?
• How do my current triglyceride levels and other risk factors guide my treatment plan?
• Are there ongoing studies or newer medications that might offer additional benefits for plaque reduction?