Effect of APOC3 Inhibition With Olezarsen on Coronary Atherosclerosis: Essence-TIMI 73b Imaging Study.

Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III, reduces triglycerides by ~60% and remnant cholesterol by ~70%, has a neutral effect on LDL (low-density lipoprotein) cholesterol (LDL-C), and reduces apoB (apolipoprotein B) by ~15% in moderate hypertriglyceridemia.

Olezarsen是一种针对载脂蛋白C-III的反义寡核苷酸，可以将甘油三酯降低约60%，将残余胆固醇降低约70%，对低密度脂蛋白胆固醇（LDL-C）有中性影响，并且在中度高甘油三酯血症中将载脂蛋白B（apoB）降低约15%。

We investigated the effect of olezarsen on coronary plaque in adults with largely moderate hypertriglyceridemia.

我们研究了olezarsen对成人大部分中度高甘油三酯血症患者冠状动脉斑块的影响。

Methods

We conducted a coronary computed tomography angiography study within Essence-TIMI 73b, a randomized, placebo-controlledtrial of olezarsen versus placebo that enrolled patients between November 2022 and February 2024.

我们在Essence-TIMI 73b研究中进行了冠状动脉计算机断层扫描血管造影研究，该研究是一项随机、安慰剂对照试验，比较olezarsen与安慰剂的效果，研究招募患者的时间为2022年11月至2024年2月。

Inclusion criteria were triglycerides ≥150 mg/dL (2.26 mmol/L), presence of or high risk for cardiovascular disease, and, for this imaging study, noncalcified plaque on baseline coronary computed tomography angiography.

纳入标准包括甘油三酯水平≥150 mg/dL (2.26 mmol/L)，存在或高风险的心血管疾病，以及对于这项影像学研究，基线冠状动脉计算机断层扫描血管造影显示非钙化斑块。

The primary end point was percent change from baseline to 12 months in noncalcified plaque volume.

主要终点是基线至12个月非钙化斑块体积的百分比变化。

Results

Of 468 participants (349 olezarsen, 119 placebo), the median age was 63 years (interquartile range, 56-70); 31% were women, and 97% received lipid-lowering therapy.

在468名参与者中（349名为olezarsen，119名为安慰剂），中位年龄为63岁（四分位数范围，56-70）；31%为女性，97%接受了降脂治疗。

Median baseline triglycerides were 249 mg/dL (interquartile range, 197-331), and remnant cholesterol was 53 mg/dL (interquartile range, 38-76).

基线甘油三酯的中位数为249 mg/dL（四分位数范围，197-331），残余胆固醇为53 mg/dL（四分位数范围，38-76）。

Median baseline noncalcified plaque volume was 125.3 mm³ (interquartile range, 63.2-213.3).

基线非钙化斑块体积的中位数为125.3 mm³（四分位数间距，63.2-213.3）。

At 6 months, olezarsen reduced triglycerides by 63.9%, remnant cholesterol by 71.9%, and apoB by 16.0% over placebo, with no difference in LDL-C.

在6个月时，olezarsen与安慰剂相比，使甘油三酯降低了63.9%，残余胆固醇降低了71.9%，载脂蛋白B降低了16.0%，但低密度脂蛋白胆固醇（LDL-C）没有差异。

The percent change in noncalcified plaque volume 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).

从基线到第12个月，非钙化斑块体积的百分比变化在olezarsen组和安慰剂组之间没有差异（安慰剂校正的最小二乘平均差异为2.98% [95% 置信区间，-3.4至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.

在12个月时，olezarsen组和安慰剂组之间在低衰减、钙化或总斑块体积的变化上没有观察到显著差异。

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.

尽管显著降低了甘油三酯和残余胆固醇，但在标准护理降脂治疗基础上，对中度高甘油三酯血症患者使用olezarsen治疗12个月，并未影响非钙化冠状动脉斑块体积。

registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT05610280.

网址: https://www.clinicaltrials.gov; 唯一标识符: NCT05610280.