Lipoprotein(a) Levels, Risk of Cardiovascular Events, and Benefit of Evolocumab: Findings From the VESALIUS-CV Trial.

Whether baseline Lp(a) identifies higher-risk patients who derive more benefit from evolocumab is not established in a population without previous myocardial infarction (MI) or stroke.

在没有既往心肌梗死（MI）或中风的患者中，基线Lp(a)是否能识别出从依洛尤单抗中获益更多的高风险患者尚未确定。

Methods

From June 2019 to November 2021, the VESALIUS-CV trial (Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarctions or Stroke) enrolled patients with qualifying atherosclerosis or high-risk diabetes without previous MI or stroke and randomized them to evolocumab or placebo (median follow-up 4.6 years).

从2019年6月到2021年11月，VESALIUS-CV试验（在无先前心肌梗死或中风的高心血管风险患者中使用依洛尤单抗的效果）招募了符合条件的动脉粥样硬化或高风险糖尿病患者，这些患者之前没有心肌梗死或中风，并将他们随机分配到依洛尤单抗组或安慰剂组（中位随访时间为4.6年）。

In a prespecified analysis, Lp(a) was assessed at baseline in 7557 patients.

在预先设定的分析中，对7557名患者在基线时进行了Lp(a)的评估。

Cox models were used to assess the adjusted risk of cardiovascular events by baseline Lp(a) in the placebo arm, and the efficacy of evolocumab by baseline Lp(a).

使用Cox模型评估了安慰剂组基线Lp(a)对心血管事件的调整风险，以及依洛尤单抗根据基线Lp(a)的疗效。

The primary outcome of interest was the composite of major coronary events (coronary heart disease death, MI, or urgent coronary revascularization).

主要关注的终点是重大冠状动脉事件（冠心病死亡、心肌梗死或紧急冠状动脉血运重建）的复合结果。

Results

Median age was 66 [interquartile range, 60-71] years, and 42.8% were women; median Lp(a) was 28 [interquartile range, 9-132] nmol/L.

中位年龄为66岁[四分位数范围，60-71岁]，女性占42.8%；中位Lp(a)为28[nmol/L，四分位数范围，9-132 nmol/L]。

Higher baseline Lp(a) was associated with an increased risk of major coronary events (adjusted hazard ratio[HRadjusted] per 100 nmol/L increase in Lp(a), 1.15 [95% CI, 1.05-1.26]; P=0.004), particularly for MI (HRadjusted, 1.23 [95% CI, 1.10-1.38]; P<0.001).

较高的基线Lp(a)水平与主要冠状动脉事件风险增加相关（每增加100 nmol/L的Lp(a)，调整后的风险比[HRadjusted]为1.15 [95% 置信区间, 1.05-1.26]；P=0.004），特别是心肌梗死（HRadjusted为1.23 [95% 置信区间, 1.10-1.38]；P<0.001）。

There was no association between Lp(a) and ischemic stroke (HRadjusted, 1.00 [95% CI, 0.84-1.19]; P=0.99).

Lp(a)与缺血性中风之间没有关联（调整后的HR，1.00 [95% 置信区间, 0.84-1.19]; P=0.99）。

After 48 weeks, evolocumab reduced LDL-C (low-density lipoprotein cholesterol) by 66.8 mg/dL and Lp(a) by 38.0 nmol/L in patients with baseline Lp(a) >105 nmol/L versus 61.1 mg/dL and 6.0 nmol/L in those with baseline Lp(a) ≤105 nmol/L.

48周后，依洛尤单抗在基线Lp(a) >105 nmol/L的患者中降低了LDL-C（低密度脂蛋白胆固醇）66.8 mg/dL和Lp(a) 38.0 nmol/L，而在基线Lp(a) ≤105 nmol/L的患者中分别降低了61.1 mg/dL和6.0 nmol/L。

The relative reductions in the rate of major coronary events were 41% (HR, 0.59 [95% CI, 0.41-0.83]) in those with Lp(a) >105 nmol/L compared with 35% (HR, 0.65 [95% CI, 0.51-0.82]) in those below (P-interaction=0.45 for Lp[a] modeled as continuous variable).

在Lp(a) >105 nmol/L的人群中，主要冠状动脉事件的发生率相对降低了41%（HR，0.59 [95% 置信区间, 0.41-0.83]），而在Lp(a)较低的人群中降低了35%（HR，0.65 [95% 置信区间, 0.51-0.82]）（将Lp[a]作为连续变量建模时的P交互作用=0.45）。

The corresponding absolute reductions were 3.7% versus 2.5% (P-interaction=0.09), corresponding to a number needed to treat of 28 versus 40 to prevent 1 major coronary event at 5 years.

相应的绝对降低分别为3.7%与2.5%（P交互作用=0.09），相当于在5年内预防1例主要冠状动脉事件，需要治疗的人数分别为28与40。

Conclusions

In patients with atherosclerosis or high-risk diabetes but without previous MI or stroke, Lp(a) was independently associated with an increased risk of major coronary events but not ischemic stroke.

在动脉粥样硬化或高风险糖尿病患者中，如果没有既往心肌梗死或中风病史，Lp(a)与主要冠状动脉事件风险增加独立相关，但与缺血性中风无关。

Evolocumab reduced the relative risk of major coronary events to a similar degree irrespective of baseline Lp(a), with a numerically greater absolute risk reduction in patients with elevated Lp(a).

无论基线Lp(a)水平如何，依洛尤单抗均以相似程度降低了主要冠状动脉事件的相对风险，而在Lp(a)水平升高的患者中，绝对风险降低数值上更大。

registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03872401.

网址: https://www.clinicaltrials.gov; 唯一标识符: NCT03872401。