A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide.

Methods

In this multinational, double-blind, randomized, placebo-controlledtrial, we enrolled adults with a history of a major atherosclerotic cardiovascular disease event with an LDL cholesterol level of 55 mg per deciliter or higher and those who were at risk for a first atherosclerotic cardiovascular disease event with an LDL cholesterol level of 70 mg per deciliter or higher.

在这项多国、双盲、随机、安慰剂对照试验中，我们招募了有重大动脉粥样硬化心血管疾病事件史且低密度脂蛋白（LDL）胆固醇水平≥55 mg/dL的成年人，以及有首次动脉粥样硬化心血管疾病事件风险且LDL胆固醇水平≥70 mg/dL的成年人。

Participants were assigned in a 2:1 ratio to receive enlicitide at a dose of 20 mg or placebo daily for 52 weeks.

参与者以2:1的比例被分配接受每日20毫克的enlicitide或安慰剂，为期52周。

The primary end point was the mean percent change in LDL cholesterol level from baseline to week 24.

主要终点是基线至第24周LDL胆固醇水平的平均百分比变化。

Key secondary end points were the mean percent change in LDL cholesterol level at week 52 and the mean percent change in levels of non-high-density lipoprotein (non-HDL) cholesterol and apolipoprotein B and the percent change in lipoprotein(a) level at week 24.

关键次要终点是第52周时LDL胆固醇水平的平均百分比变化，以及第24周时非高密度脂蛋白(non-HDL)胆固醇、载脂蛋白B水平的平均百分比变化和脂蛋白(a)水平的百分比变化。

Results

Of the 2909 participants in the intention-to-treatpopulation, 1935 received enlicitide and 969 received placebo (5 did not receive enlicitide or placebo).

在意向治疗人群中，共有2909名参与者，其中1935人接受了enlicitide治疗，969人接受了安慰剂（5人未接受enlicitide或安慰剂）。

The mean age of the participants was 63 years, and 39.3% were women.

参与者的平均年龄为63岁，其中39.3%为女性。

The mean (±SD) LDL cholesterol level at baseline was 96.1±38.9 mg per deciliter.

基线时的平均（±标准差）低密度脂蛋白胆固醇水平为96.1±38.9毫克/分升。

The mean percent change in LDL cholesterol levels at week 24 was -57.1% (95% confidence interval[CI], -61.8 to -52.5) with enlicitide and 3.0% (95% CI, 0.9 to 5.1) with placebo, representing an adjusted between-group difference of -55.8 percentage points (95% CI, -60.9 to -50.7; P<0.001).

在第24周，使用enlicitide的LDL胆固醇水平平均变化百分比为-57.1%（95%置信区间[CI]，-61.8至-52.5），而使用安慰剂的为3.0%（95% CI，0.9至5.1），调整后的组间差异为-55.8个百分点（95% CI，-60.9至-50.7；P<0.001）。

The mean percent change in LDL cholesterol level at week 52, the mean percent changes in non-HDL cholesterol and apolipoprotein B levels at week 24, and the percent change in lipoprotein(a) levels at week 24 were significantly greater with enlicitide than with placebo (P<0.001 for all comparisons).

在第52周，使用enlicitide的LDL胆固醇水平平均变化百分比，以及在第24周非HDL胆固醇和载脂蛋白B水平的平均变化百分比，以及脂蛋白(a)水平的变化百分比均显著高于使用安慰剂的（所有比较的P<0.001）。

The incidenceof adverse events did not appear to differ between the groups.

两组之间不良事件的发生率似乎没有差异。

Conclusions

Among participants who had a history of or were at risk for a first atherosclerotic cardiovascular disease event, treatment with the oral PCSK9 inhibitor enlicitide resulted in significantly lower LDL cholesterol levels than placebo at 24 weeks.

在有动脉粥样硬化心血管疾病事件史或风险的参与者中，口服PCSK9抑制剂enlicitide治疗在24周时的LDL胆固醇水平显著低于安慰剂。

(Funded by MSD [Rahway, NJ]; CORALreef Lipids ClinicalTrials.gov number, NCT05952856.).

(由默沙东公司[新泽西州拉霍瓦]资助; CORALreef Lipids ClinicalTrials.gov编号, NCT05952856.)。