Olpasiran, Oxidized Phospholipids, and Systemic Inflammatory Biomarkers: Results From the OCEAN(a)-DOSE Trial.

OxPL are believed to be a potent driver of inflammation and atherosclerosis.

OxPL被认为是炎症和动脉粥样硬化的强效驱动因素。

Olpasiran, a small interfering RNA, blocks Lp(a) production by inducing degradation of apolipoprotein(a) messenger RNA.

Olpasiran是一种小干扰RNA，通过诱导载脂蛋白(a)信使RNA的降解来阻断Lp(a)的产生。

Olpasiran's effects on OxPL and systemic markers of inflammation are not well described.

Olpasiran对氧化磷脂(OxPL)和全身炎症标志物的影响尚未得到充分描述。

Background

To assess the effects of olpasiran on OxPL, high-sensitivity interleukin 6 (hs-IL-6), and hs-C-reactive protein (hs-CRP) in the OCEAN(a)-DOSE randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: OCEAN(a)-DOSE was an international, multicenter, placebo-controlled, phase 2, dose-finding randomized clinical trial conducted between July 2020 and November 2022.

评估olpasiran对OCEAN(a)-DOSE随机临床试验中氧化磷脂(OxPL)、高灵敏度白细胞介素6（hs-IL-6）和高灵敏度C反应蛋白（hs-CRP）的影响。

A total of 281 patients with atherosclerotic cardiovascular disease and Lp(a) levels greater than 150 nmol/L were included.

共有281名动脉粥样硬化心血管疾病患者和Lp(a)水平超过150 nmol/L的患者被纳入研究。

intervention

Participants were randomized to receive 1 of 4 active subcutaneous doses of olpasiran vs placebo: (1) 10 mg, administered every 12 weeks (Q12W); (2) 75 mg, Q12W; (3) 225 mg, Q12W; or (4) 225 mg, administered every 24 weeks (Q24W).

参与者被随机分配接受奥帕萨兰的4种活性皮下剂量之一与安慰剂：(1) 每12周（Q12W）给予10毫克；(2) 每12周（Q12W）给予75毫克；(3) 每12周（Q12W）给予225毫克；或(4) 每24周（Q24W）给予225毫克。

OxPL on apolipoprotein B (OxPL-apoB), hs-CRP, and hs-IL-6 were assessed at baseline, week 36, and week 48 in 272 patients.

在272名患者中，于基线、第36周和第48周评估了氧化磷脂酰胆碱与载脂蛋白B（OxPL-apoB）、高敏C反应蛋白（hs-CRP）和高敏白细胞介素6（hs-IL-6）。

main_outcomes_and_measures

The primary outcome was placebo-adjusted change in OxPL-apoB from baseline to week 36.

主要结果是基线至第36周时，与安慰剂相比，OxPL-apoB的变化。

Results

Among 272 participants, median (IQR) age was 62 years (56-69), and 86 participants (31.6%) were female.

在272名参与者中，中位年龄为62岁（四分位数间距为56-69岁），86名参与者（31.6%）为女性。

Baseline median (IQR) Lp(a) concentration was 260.3 nmol/L (198.1-352.4) and median (IQR) OxPL-apoB concentration was 26.5 nmol/L (19.7-33.9).

基线中位数（四分位数间距）Lp(a)浓度为260.3 nmol/L（198.1-352.4），中位数（四分位数间距）OxPL-apoB浓度为26.5 nmol/L（19.7-33.9）。

The placebo-adjusted mean percentage change in OxPL-apoB from baseline to week 36 was -51.6% (95% CI, -64.9% to -38.2%) for the 10-mg Q12W dose, -89.7% (95% CI, -103.0% to -76.4%) for the 75-mg Q12W dose, -92.3% (95% CI, -105.6% to -78.9%) for the 225-mg Q12W dose, and -93.7% (95% CI, -107.1% to -80.3%) for the Q24W dose (P < .001 for all).

与安慰剂相比，从基线到第36周，10毫克每12周剂量的OxPL-apoB平均百分比变化为-51.6%（95% 置信区间, -64.9%至-38.2%），75毫克每12周剂量的为-89.7%（95% 置信区间, -103.0%至-76.4%），225毫克每12周剂量的为-92.3%（95% 置信区间, -105.6%至-78.9%），以及每24周剂量的为-93.7%（95% 置信区间, -107.1%至-80.3%）（所有P < .001）。

These effects were maintained to week 48 (-50.8%, -100.2%, -104.7%, and -85.8%, respectively; P < .001 for all).

这些效果在第48周时仍然维持（分别为-50.8%，-100.2%，-104.7%和-85.8%；所有P < .001）。

There was a strong correlation between percentage reduction in Lp(a) and OxPL-apoB for patients treated with olpasiran (r = 0.79; P < .001).

在接受奥帕萨利单抗治疗的患者中，Lp(a)的百分比降低与OxPL-apoB之间存在强烈的相关性（r = 0.79；P < .001）。

Olpasiran did not significantly impact hs-CRP or hs-IL-6 compared with placebo to weeks 36 or 48 (P > .05).

在OCEAN(a)-DOSE多中心随机临床试验中，Olpasiran导致OxPL-apoB显著且持续降低，但对hs-CRP或hs-IL-6没有显著影响。

conclusion_and_relevance

In the OCEAN(a)-DOSE multicenter randomized clinical trial, olpasiran led to a significant and sustained reduction in OxPL-apoB but no significant effects on hs-CRP or hs-IL-6.

在OCEAN(a)-DOSE多中心随机临床试验中，olpasiran导致OxPL-apoB显著且持续降低，但对hs-CRP或hs-IL-6没有显著影响。