Antibody-mediated LOX-1 inhibition in patients with residual inflammation after myocardial infarction: a randomized phase 2 trial.

Here we evaluated MEDI6570, an antibody that acts as a LOX-1 antagonist, in a randomized, double-blind, dose-finding study in patients with myocardial infarction (MI) and residual inflammation (high-sensitivity C-reactive protein ≥ 1 mg l-1).

在这里，我们评估了MEDI6570，一种作为LOX-1拮抗剂的抗体，在一项随机、双盲、剂量探索研究中，研究对象为心肌梗死（MI）患者且存在残余炎症（高敏C反应蛋白≥1 mg l-1）。

At 30-365 days after MI, 423 patients (75 women, 348 men) were randomly allocated to 50 mg, 150 mg or 400 mg MEDI6570 or placebo treatment subcutaneously every 4 weeks for 32 weeks.

在心肌梗死（MI）后30-365天，423名患者（75名女性，348名男性）被随机分配接受50 mg、150 mg或400 mg MEDI6570或安慰剂皮下注射治疗，每4周一次，持续32周。

The primary endpoint, the change in the noncalcified plaque volume in the most diseased coronary segment (NCPVMD) by computed tomography angiography, was not significantly different between placebo and MEDI6570 at any dose.

主要终点，即通过计算机断层扫描血管造影测量的最严重冠状动脉段非钙化斑块体积（NCPVMD）的变化，在任何剂量的安慰剂和MEDI6570之间没有显著差异。

The secondary endpoints, global NCPV and low-attenuation plaque volume, were also not different between placebo and MEDI6570 at any dose (all placebo-adjusted comparisons, P > 0.05).

次要终点，包括总体非钙化斑块体积（global NCPV）和低密度斑块体积，在安慰剂组和任何剂量的MEDI6570之间也没有差异（所有安慰剂调整后的比较，P > 0.05）。

With regard to exploratory endpoints, there were reductions in free soluble LOX-1 (sLOX-1) from baseline by 44.8%, 85.8%, 94.0% and 96.4% in the placebo, 50 mg, 150 mg and 400 mg dose arms, respectively (all placebo-adjusted comparisons P < 0.001).

关于探索性终点，从基线开始，安慰剂组、50毫克、150毫克和400毫克剂量组的自由可溶性LOX-1（sLOX-1）分别降低了44.8%、85.8%、94.0%和96.4%（所有安慰剂调整后的比较P < 0.001）。

Interleukin-6 (IL-6) levels decreased by 2.9%, -3.0%, 18.9% and 21.5% in the placebo, 50 mg, 150 mg and 400 mg arms, respectively, with substantial placebo-adjusted reductions observed only at 150 mg and 400 mg (P < 0.05).

在安慰剂组、50 mg组、150 mg组和400 mg组中，白细胞介素-6（IL-6）水平分别下降了2.9%、-3.0%、18.9%和21.5%，仅在150 mg和400 mg组观察到与安慰剂相比显著的降低（P < 0.05）。

MEDI6570 was well tolerated and rates of serious adverse events were similar in the MEDI6570 and placebo groups.

MEDI6570耐受性良好，严重不良事件的发生率在MEDI6570组和安慰剂组中相似。

In summary, despite favorable effects on sLOX-1 and IL-6, a LOX-1 inhibitor did not reduce noncalcified coronary plaque volume in patients with residual inflammation after acute MI.

总结来说，尽管对sLOX-1和IL-6有积极影响，但在急性心肌梗死（MI）后仍有残余炎症的患者中，LOX-1抑制剂并未减少非钙化冠状动脉斑块体积。

EudraCT registration: 2020-000840-75 .

EudraCT注册号：2020-000840-75。