本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2402309

摘要内容如下：

背景

降低甘油三酯和富含甘油三酯的脂蛋白的水平仍然是尚未满足的临床需求。Olezarsen是一种针对载脂蛋白C-III（APOC3）的信使RNA的反义寡核苷酸，APOC3是一种经遗传验证的降低甘油三酯的靶标。

方法

在这项2B期随机对照试验中，我们将中度高甘油三酯血症（甘油三酯水平为150-499 mg/DL）和心血管风险升高或重度高甘油三酯血症（甘油三酯水平≥500 mg/DL）的成人按1:1的比例分配到50 mg或80 mg队列中。然后以3:1的比例分配患者，在每个队列中接受每月皮下注射Olezarsen或匹配的安慰剂。主要转归是甘油三酯水平从基线到6个月的百分比变化，报告为每个Olezarsen组和安慰剂组之间的差异。关键的次要转归是APOC3、载脂蛋白B、非高密度脂蛋白（HDL）胆固醇和低密度脂蛋白（LDL）胆固醇水平的变化。

结果

共有154名患者在北美的24个地点接受了随机分组。患者的中位年龄为62岁，中位甘油三酯水平为241.5 mg/DL。与安慰剂相比，50 mg和80 mg剂量的Olezarsen分别降低了49.3个百分点和53.1个百分点的甘油三酯水平（两项比较P<0.001）。与安慰剂相比，每个剂量的Olezarsen还显著降低了ApoC3、载脂蛋白B和非HDL胆固醇的水平，而LDL胆固醇水平没有显著变化。三组患者发生不良事件和严重不良事件的风险相似。有临床意义的肝、肾或血小板异常并不常见，三组风险相似。

结论

在心血管风险升高的中度高甘油三酯血症患者中，Olezarsen显著降低了甘油三酯、载脂蛋白B和非高密度脂蛋白胆固醇的水平，未发现重大安全问题。（由Ionis Pharmaceuticals资助；Bridge-TIMI 73A ClinicalTrials.gov编号，NCT05355402。）

英文原文如下：

Abstracts

BACKGROUND  Reducing the levels of triglycerides and triglyceride-rich lipoproteins remains an unmet clinical need. Olezarsen is an antisense oligonucleotide targeting messenger RNA for apolipoprotein C-III (APOC3), a genetically validated target for triglyceride lowering.

METHODS  In this phase 2b, randomized, controlled trial, we assigned adults either with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) in a 1:1 ratio to either a 50-mg or 80-mg cohort. Patients were then assigned in a 3:1 ratio to receive monthly subcutaneous olezarsen or matching placebo within each cohort. The primary outcome was the percent change in the triglyceride level from baseline to 6 months, reported as the difference between each olezarsen group and placebo. Key secondary outcomes were changes in levels of APOC3, apolipoprotein B, non-high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol.

RESULTS  A total of 154 patients underwent randomization at 24 sites in North America. The median age of the patients was 62 years, and the median triglyceride level was 241.5 mg per deciliter. The 50-mg and 80-mg doses of olezarsen reduced triglyceride levels by 49.3 percentage points and 53.1 percentage points, respectively, as compared with placebo (P<0.001 for both comparisons). As compared with placebo, each dose of olezarsen also significantly reduced the levels of APOC3, apolipoprotein B, and non-HDL cholesterol, with no significant change in the LDL cholesterol level. The risks of adverse events and serious adverse events were similar in the three groups. Clinically meaningful hepatic, renal, or platelet abnormalities were uncommon, with similar risks in the three groups.

CONCLUSIONS  In patients with predominantly moderate hypertriglyceridemia at elevated cardiovascular risk, olezarsen significantly reduced levels of triglycerides, apolipoprotein B, and non-HDL cholesterol, with no major safety concerns identified. (Funded by Ionis Pharmaceuticals; Bridge-TIMI 73a ClinicalTrials.gov number, NCT05355402.).

-----------分割线---------

点击链接：https://www.mediecogroup.com/community/user/vip/categories/ ，成为医咖会员，获取12项专属权益。