Olezarsen did not affect noncalcified coronary plaque volume in patients with moderate hypertriglyceridemia, despite substantial triglyceride and remnant cholesterol lowering.
Does olezarsen improve noncalcified coronary plaque volume in patients with largely moderate hypertriglyceridemia?
Olezarsen effectively lowers triglycerides and remnant cholesterol but does not reduce noncalcified coronary plaque volume over 12 months in patients with moderate hypertriglyceridemia.
Absolute Event Rate: 0% vs 0%
BACKGROUND: Whether lowering triglyceride-rich lipoproteins and remnant cholesterol favorably modifies coronary atherosclerosis is unclear. Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III, reduces triglycerides by ~60% and remnant cholesterol by ~70%, has a neutral effect on LDL cholesterol (LDL-C), and reduces apolipoprotein B (apoB) by ~15% in moderate hypertriglyceridemia. We investigated the effect of olezarsen on coronary plaque in adults with largely moderate hypertriglyceridemia. METHODS: We conducted a coronary computed tomography angiography (CCTA) study within Essence-TIMI 73b, a randomized, placebo-controlled trial of olezarsen vs. placebo that enrolled patients between November 2022 and February 2024. Inclusion criteria were triglycerides ≥150 mg/dL (2.26 mmol/L), presence or high risk for cardiovascular disease, and non-calcified plaque on baseline CCTA. The primary endpoint was percent change from baseline to 12 months in non-calcified plaque volume (NCPV). RESULTS: Of 468 participants (349 olezarsen, 119 placebo), the median age was 63 years (IQR 56-70); 31% were women, and 97% received lipid-lowering therapy. Median baseline triglycerides were 249 mg/dL (IQR 197-331), and remnant cholesterol was 53 mg/dL (IQR 38-76). Median baseline NCPV was 125.3 mm³ (IQR 63.2-213.3). At 6 months, olezarsen reduced triglycerides by 63.9%, remnant cholesterol by 71.9%, and apolipoprotein B by 16.0% over placebo, with no difference in LDL-C. The percent change in NCPV with olezarsen from baseline to month 12 did not differ between olezarsen and placebo (placebo-adjusted least-squares mean difference 2.98%; 95% CI -3.4 to 9.3; p=0.36). No significant differences between olezarsen and placebo were observed for changes in low-attenuation, calcified, or total plaque volumes at 12 months. CONCLUSIONS: Despite substantial triglyceride and remnant cholesterol lowering, treatment with olezarsen for 12 months on top of standard-of-care lipid-lowering therapy in patients with largely moderate hypertriglyceridemia did not affect noncalcified coronary plaque volume.
“This is an important trial looking at a group that we see a lot in clinical practice. We know historically that this group has increased residual risk when they’re optimized on lifestyle, which is [where] we first start with triglyceride lowering.”
ACC.26 presentation and Circulation publication; part of aggressive lipid lowering narrative with 10+ news stories on cholesterol drugs; high interest in new lipid targets beyond LDL.
Marston et al. (Mon,) reported a other. Olezarsen did not affect noncalcified coronary plaque volume in patients with moderate hypertriglyceridemia, despite substantial triglyceride and remnant cholesterol lowering.