Bempedoic Acid and First and Recurrent Limb Outcomes in Statin-Intolerant Patients With Peripheral Artery Disease: Insights From the CLEAR Outcomes Trial.

Recently, bempedoic acid was shown to reduce MACE in primary and secondary prevention patients.

最近的研究显示，贝美多酸可以降低一级和二级预防患者的MACE风险。

Whether bempedoic acid reduces the risk of MALE in patients with PAD is unknown.

贝美多酸是否能降低PAD患者的MALE风险尚不清楚。

Methods

CLEAR Outcomes (Cholesterol Lowering via Bempedoic Acid [ETC1002], an ACL-Inhibiting Regimen) randomized 13 970 patients to bempedoic acid 180 mg or placebo from December 22, 2016, to August 14, 2019.

CLEAR Outcomes（通过贝美多酸[ETC1002]降低胆固醇，一种ACAT抑制剂方案）从2016年12月22日至2019年8月14日，随机分配了13970名患者接受180毫克的贝美多酸或安慰剂。

The trial primary end point was MACE-4, defined as death resulting from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.

试验的主要终点是MACE-4，定义为心血管原因导致的死亡、非致命性心肌梗死、非致命性中风或冠状动脉血运重建。

A clinical history of PAD was reported by investigators at baseline.

基线时，调查员报告了PAD的临床病史。

Two blinded vascular medicine specialists independently adjudicated MALE, including adverse events indicating worsening PAD symptoms leading to revascularization, chronic limb-threatening ischemia, and acute limb ischemia.

两名盲法血管医学专家独立判定MALE，包括导致血运重建的恶化PAD症状、慢性肢体威胁性缺血和急性肢体缺血的不良事件。

Outcomes were assessed as time to first event and total (including recurrent) events with a negative binomial approach.

结果以首次事件的时间和总事件（包括复发）进行评估，采用负二项式方法。

Results

A total of 1624 of the enrolled patients (mean±SD age, 63.9±9.9 years; 915 [56.3%] female) had PAD at baseline.

共有1624名入组患者（平均年龄63.9±9.9岁；915名[56.3%]为女性）在基线时患有周围动脉疾病（PAD）

In patients with PAD in the placebo group, 69 (8.3%) had MALE over a median of 40.6 months, with rate of recurrent events of 4.0%/y.

在安慰剂组的PAD患者中，69名（8.3%）在中位40.6个月的时间里发生了重大动脉事件（MALE），复发事件率为每年4.0%。

Bempedoic acid reduced the risk of MALE by 36% (hazard ratio, 0.64 [95% CI, 0.44-0.93]; P=0.018).

贝美多酸降低了MALE风险36%（风险比，0.64 [95% CI, 0.44-0.93]；P=0.018）。

Bempedoic acid reduced total MALE by 45% (relative risk, 0.55 [95% CI, 0.35-0.85]; P=0.007).

贝美多酸总共降低了MALE 45%（相对风险，0.55 [95% CI, 0.35-0.85]；P=0.007）。

First MACE-4 or MALE was reduced overall by 13% (hazard ratio, 0.87 [95% CI, 0.80-0.95]) with consistent effects with PAD (hazard ratio, 0.82 [95% CI, 0.64-1.04]) and without PAD (hazard ratio, 0.87 [95% CI, 0.79-0.86]; Pinteraction=NS) but not statistically significant within the PAD subgroup alone.

首次主要不良心血管事件（MACE-4）或MALE总体降低了13%（风险比，0.87 [95% CI, 0.80-0.95]），对PAD（风险比，0.82 [95% CI, 0.64-1.04]）和非PAD（风险比，0.87 [95% CI, 0.79-0.86]；Pinteraction=NS）均有持续效果，但在PAD亚组内单独统计学上并不显著。

Total MACE-4 or MALE was reduced (relative risk, 0.81 [95% CI, 0.73-0.90]) overall with consistent effects in PAD (relative risk, 0.71 [95% CI, 0.54-0.95]) and without PAD (relative risk, 0.82 [95% CI, 0.73-0.92]; Pinteraction=NS).

总体上，MACE-4或MALE的总风险降低了（相对风险，0.81 [95% CI, 0.73-0.90]），在PAD（相对风险，0.71 [95% CI, 0.54-0.95]）和非PAD（相对风险，0.82 [95% CI, 0.73-0.92]；Pinteraction=NS）中均有持续效果。

Conclusions

Patients with PAD are at high risk of MALE and MACE.

PAD患者有很高的MALE和MACE风险。

Bempedoic acid reduces both MACE and MALE in patients with atherosclerotic vascular disease, with notable absolute benefits in patients with PAD.

贝美多酸在动脉粥样硬化性血管疾病患者中降低了MACE和MALE，对PAD患者的绝对益处显著。

These findings support (1) the importance of lowering low-density lipoprotein cholesterol in patients with PAD to reduce overall vascular risk and (2) the benefits of bempedoic acid in this population.

这些发现支持以下两点：(1)降低外周动脉疾病患者的低密度脂蛋白胆固醇对于降低总体血管风险的重要性；(2)在这一人群中，苯普酸的益处。