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ESSENCE-TIMI 73bLipid / PreventionCirculation
Effect of Olezarsen on Coronary Atherosclerosis in the Essence–TIMI 73b Imaging Study
Effect of APOC3 Inhibition with Olezarsen on Coronary Atherosclerosis: Essence–TIMI 73b Imaging Study
View Full PaperWhy the trial?
The trial was conducted to evaluate whether olezarsen treatment, in addition to standard lipid-lowering therapy, could reduce noncalcified coronary plaque volume in patients with moderate hypertriglyceridemia.
Does olezarsen improve noncalcified coronary plaque volume in patients with largely moderate hypertriglyceridemia?
Key result
Olezarsen did not affect noncalcified coronary plaque volume in patients with moderate hypertriglyceridemia, despite substantial triglyceride and remnant cholesterol lowering.
Authors
Discussion
Key questions
Member takes
Where experts stand
Despite dramatic triglyceride lowering, olezarsen failed to reduce coronary plaque on imaging, and experts agree that a cardiovascular outcomes trial is needed to determine whether this lipid pathway translates to clinical benefit.
Olezarsen produced large triglyceride and remnant cholesterol reductions but no measurable effect on coronary plaque volume at 12 months, leaving experts cautious about its cardiovascular promise beyond rare genetic conditions. The trial investigators emphasize the robust lipid changes while acknowledging the neutral imaging finding. The central open question is whether a dedicated outcomes trial can demonstrate that long-term inhibition of this pathway actually prevents cardiovascular events.
Agreement
Multiple experts converge on the disconnect between olezarsen's substantial triglyceride lowering and the absence of a plaque effect, framing a cardiovascular outcomes trial as the necessary next step.
2 clinicians say this directly
Still unclear
Whether long-term ApoC3 inhibition translates into cardiovascular event reduction remains unanswered, as the plaque imaging results were neutral. It is also unclear whether combining olezarsen with another lipid-lowering therapy might yield a different outcome, a possibility raised by the presenting investigator.
Key expert perspectives
BNBørge NordestgaardProfessor, Copenhagen University HospitalPractice takeMar 31
Nordestgaard called the trial results very, very important
Nordestgaard described the findings as "very, very important," signaling the significance of the data for the field, though he did not elaborate on clinical implications.
Distilled from their postOriginal post
NMNicholas MarstonCardiologist, Brigham and Women's HospitalResults readoutMar 31
Olezarsen lowers triglycerides and remnant cholesterol but did not move coronary plaque
Marston presented the findings showing that olezarsen on top of standard lipid-lowering therapy substantially lowered triglycerides and remnant cholesterol and modestly lowered ApoB, but did not affect non-calcified coronary plaque volume at 12 months. He emphasized that a cardiovascular outcomes trial is needed to determine the benefit of long-term ApoC3 inhibition, whether tested as monotherapy or in combination.
BBBrian BergmarkInterventional cardiologist, Brigham and Women's HospitalContextMar 31
Trial provides good lipid data but olezarsen's broader efficacy and safety are not yet established
Bergmark highlighted that olezarsen produced substantial triglyceride lowering beyond what current therapies achieve, with over 80% of treated patients reaching normal levels. He noted the drug is approved only for familial chylomicronemia syndrome and that its efficacy and safety in the broader hypertriglyceridemia population remain unproven.
Overview
Clinicians should not anticipate plaque benefit from olezarsen; challenges the triglyceride hypothesis for atherosclerosis progression.
Key Points
- This research aimed to determine if olezarsen could reduce coronary plaque volume in patients with moderate hypertriglyceridemia.
- Conducted a randomized, placebo-controlled trial within Essence-TIMI 73b.
- Enrolled adults with triglycerides ≥150 mg/dL and documented coronary artery disease.
- Measured changes in non-calcified plaque volume at baseline and 12 months using coronary computed tomography angiography.
- Olezarsen reduced triglycerides by 63.9% and remnant cholesterol by 71.9% but did not change non-calcified plaque volume (p=0.36).
- No significant differences in plaque volume types (low-attenuation, calcified, total) were observed between olezarsen and placebo.
- Results indicate that despite lipid lowering, olezarsen had no beneficial effect on coronary atherosclerosis.
Structured PICO
Does olezarsen improve noncalcified coronary plaque volume in patients with largely moderate hypertriglyceridemia?
P
Population
patients with largely moderate hypertriglyceridemia
I
Intervention
olezarsen for 12 months on top of standard-of-care lipid-lowering therapy
O
Outcome
noncalcified coronary plaque volumesurrogate
Olezarsen effectively lowers triglycerides and remnant cholesterol but does not reduce noncalcified coronary plaque volume over 12 months in patients with moderate hypertriglyceridemia.
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Marston et al. (2026) studied this question. Olezarsen did not affect noncalcified coronary plaque volume in patients with moderate hypertriglyceridemia, despite substantial triglyceride and remnant cholesterol lowering.