Evolocumab in Patients without a Previous Myocardial Infarction or Stroke.

The effect of evolocumab on the risk of MACE among patients without a previous myocardial infarction or stroke is unknown.

依洛尤单抗对既往无心肌梗死或中风患者发生MACE风险的影响尚不明确。

Methods

We conducted an international, double-blind, randomized, placebo-controlledtrial of evolocumab in patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke who had a low-density lipoprotein cholesterol level of at least 90 mg per deciliter.

我们开展了一项国际、双盲、随机、安慰剂对照的 evolocumab 试验，对象为动脉粥样硬化或糖尿病患者，且之前未发生过心肌梗死或中风，这些患者的低密度脂蛋白胆固醇水平至少为每分升 90 毫克。

Patients were randomly assigned in a 1:1 ratio to receive evolocumab at a dose of 140 mg every 2 weeks or placebo.

患者按 1:1 的比例随机分配，接受每两周 140 毫克的 evolocumab 或安慰剂治疗。

The two primary end points were a composite of death from coronary heart disease, myocardial infarction, or ischemic stroke (3-point MACE) and a composite of 3-point MACE or ischemia-driven arterial revascularization (4-point MACE).

两个主要终点是冠心病、心肌梗死或缺血性中风死亡的复合终点（3点MACE）以及3点MACE或缺血驱动的动脉血运重建的复合终点（4点MACE）。

Results

A total of 12,257 patients were randomly assigned to receive evolocumab (6129 patients) or placebo (6128) and were included in the efficacy analyses.

共有12,257名患者被随机分配接受evolocumab治疗（6129名患者）或安慰剂（6128名），并纳入了疗效分析。

The median age of the patients was 66 years, 43% were women, and 93% were White.

患者的中位年龄为66岁，43%为女性，93%为白人。

The median follow-up was 4.6 years.

中位随访时间为4.6年。

A 3-point MACE event occurred in 336 patients (5-year Kaplan-Meier estimate, 6.2%) in the evolocumab group, as compared with 443 (8.0%) in the placebo group (hazard ratio, 0.75; 95% confidence interval[CI], 0.65 to 0.86; P<0.001).

在 evolocumab 组中，336名患者发生了3点主要不良心血管事件（MACE），5年Kaplan-Meier估计发生率为6.2%，相比之下，安慰剂组为443例（发生率为8.0%）（风险比，0.75；95%置信区间[CI]，0.65至0.86；P<0.001）。

A 4-point MACE event occurred in 747 patients (5-year Kaplan-Meier estimate, 13.4%) in the evolocumab group, as compared with 907 (16.2%) in the placebo group (hazard ratio, 0.81; 95% CI, 0.73 to 0.89; P<0.001).

在 evolocumab 组中，747名患者发生了4点主要不良心血管事件（MACE），5年Kaplan-Meier估计发生率为13.4%，相比之下，安慰剂组为907例（发生率为16.2%）（风险比，0.81；95%置信区间[CI]，0.73至0.89；P<0.001）。

No evidence of a between-group difference was seen in the incidenceof safety events.

未观察到两组间安全事件发生率的差异。

Conclusions

PCSK9 inhibition with evolocumab led to a lower risk of first cardiovascular events than placebo among patients with atherosclerosis or diabetes and without a previous myocardial infarction or stroke.

在动脉粥样硬化或糖尿病患者中，与安慰剂相比，使用依洛尤单抗（evolocumab）抑制PCSK9可降低首次心血管事件的风险，前提是这些患者之前没有心肌梗死或中风。

(Funded by Amgen; VESALIUS-CV ClinicalTrials.gov number, NCT03872401.).

(由安进公司资助; VESALIUS-CV 临床试验注册号, NCT03872401.)