Clinical Trial Data Reveals Potent Triglyceride Lowering Drug Olezarsen Fails to Reduce Coronary Plaque Volume After One Year of Treatment

ACC.26 study shows olezarsen reduced triglycerides by 60% but failed to change non-calcified coronary plaque volume after one year of treatment.

By: AXL Media

Published: Mar 31, 2026, 4:10 AM EDT

Source: Information for this report was sourced from American College of Cardiology

A Disconnect Between Blood Chemistry and Arterial Health

The medical community has long recognized elevated triglycerides as a primary marker for cardiovascular risk, yet treating this specific factor has rarely produced the same clear benefits as lowering LDL cholesterol. New data from the Essence-TIMI 73b sub-study, presented at the American College of Cardiology’s Annual Scientific Session, reinforces this complexity. Researchers found that patients at high risk of atherosclerosis who took the drug olezarsen saw their triglyceride levels plummet, but the physical buildup of soft, non-calcified plaque in their coronary arteries remained unchanged. This suggests that while blood markers may improve rapidly, the reversal or stabilization of the plaques responsible for heart attacks and strokes is a far more resistant process.

Targeting Apolipoprotein C3 to Regulate Fat Metabolism

Olezarsen functions by inhibiting apolipoprotein C3, a protein that plays a vital role in how the body metabolizes triglycerides. By targeting this specific pathway, the drug serves as a unique test case for researchers attempting to isolate the role of triglycerides in heart disease, independent of LDL cholesterol. In the study, 468 participants with triglyceride levels over 150 mg/dL were monitored using coronary computed tomography angiography (CCTA), a high-resolution imaging technique. Despite a 60% reduction in triglycerides and a modest 15% lowering of apolipoprotein B, the imaging showed that the physical volume of arterial "gunk" did not decrease over the 12-month period.

The Resilience of Non-Calcified Coronary Plaque

The primary focus of the imaging sub-study was non-calcified plaque, the "soft" buildup that is particularly dangerous because it is prone to rupturing and causing sudden blockages. Researchers had hypothesized that a massive reduction in circulating fat particles would at least slow the progression of these soft deposits. However, the results revealed no significant difference between those receiving olezarsen and those on a placebo. Lead author Nicholas Marston, a cardiologist at Brigham and Women’s Hospital, noted that while the drug effectively altered blood components, these changes did not translate into an immediate structural benefit for the coronary arteries of patients with moderate hypertriglyceridemia.