Obesity-Associated Cardiovascular Risk and Benefit From PCSK9 Inhibition: A Prespecified Analysis From FOURIER.

The relationship between body mass index (BMI) and benefit of evolocumab remains unknown.

身体质量指数（BMI）与依洛尤单抗的益处之间的关系尚不明确。

This study sought to investigate the association between BMI, risk of MACE, and the clinical benefit of evolocumab.

本研究旨在调查体质指数（BMI）、主要不良心血管事件（MACE）风险以及依洛尤单抗的临床益处之间的关联。

Methods

The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial randomized 27,564 stable atherosclerotic cardiovascular disease patients to evolocumab or placebo (median follow-up 2.2 years).

FOURIER（进一步研究PCSK9抑制对高危患者心血管结果的影响）试验随机将27,564名稳定动脉粥样硬化心血管疾病患者分配到依洛尤单抗组或安慰剂组（中位随访时间为2.2年）。

The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.

主要终点是心血管死亡、心肌梗死、中风、不稳定型心绞痛住院或冠状动脉血运重建。

The association between BMI and cardiovascular risk was examined in the placebo arm adjusting for clinical predictors.

在安慰剂组中，调整了临床预测因素后，检查了体质指数（BMI）与心血管风险之间的关联。

Effect modification by treatment arm was assessed using an interaction term in the Cox model.

使用Cox模型中的交互项评估了治疗组的效果修饰作用。

Kaplan-Meier rates are at 3 years.

Kaplan-Meier生存率在3年时的数据。

Results

A total of 10,942 (40%) participants had a BMI ≥30 kg/m2; 3,446 (13%) had a BMI ≥35 kg/m2.

共有10,942名（40%）参与者BMI ≥30 kg/m2；3,446名（13%）BMI ≥35 kg/m2。

In the placebo arm, for every 5-unit-higher BMI above 30 kg/m2, there was an 11% higher risk of the primary endpoint (adjusted HR: 1.11; 95% CI: 1.02-1.21).

在安慰剂组中，BMI每高出30 kg/m2 5个单位，主要终点事件的风险就增加11%（调整后的HR: 1.11; 95% CI: 1.02-1.21）。

The relative risk reduction for the primary endpoint with evolocumab was progressively greater in those with BMI ≥30 kg/m2 modeled on a continuous basis (P for interaction = 0.025).

在BMI ≥30 kg/m2的人群中，使用依洛珠单抗对主要终点的相对风险降低效果在连续性模型中逐渐增大（交互作用P值=0.025）。

Evolocumab reduced the risk of the primary endpoint by 11% in those with a BMI <30 kg/m2 (HR: 0.89; 95% CI: 0.81-0.98), by 14% in those with BMI of 30 to <35 kg/m2 (HR: 0.86; 95% CI: 0.75-0.98), and by 29% in those with BMI ≥35 kg/m2 (HR: 0.71; 95% CI: 0.59-0.86).

依洛珠单抗在BMI <30 kg/m2的人群中将主要终点风险降低了11%（HR: 0.89; 95% 置信区间: 0.81-0.98），在BMI为30至<35 kg/m2的人群中降低了14%（HR: 0.86; 95% 置信区间: 0.75-0.98），而在BMI ≥35 kg/m2的人群中降低了29%（HR: 0.71; 95% 置信区间: 0.59-0.86）。

The corresponding absolute risk reductions were 1.4%, 1.8%, and 5.7%, respectively.

相应的绝对风险降低分别为1.4%，1.8%和5.7%。

Conclusions

Individuals with obesity and atherosclerotic cardiovascular disease face an elevated risk of MACE compared with those without obesity, and evolocumab helps to attenuate this risk.

肥胖和动脉粥样硬化性心血管疾病的个体与没有肥胖的个体相比，面临主要不良心血管事件（MACE）的增加风险，而依洛尤单抗有助于减轻这一风险。