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依洛尤单抗对心肌梗死后他汀类药物治疗患者的冠状动脉斑块表型和负担的影响。

Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction.

机构信息

Victorian Heart Institute, Monash University, Clayton, Australia.

Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Suita, Japan.

出版信息

JACC Cardiovasc Imaging. 2022 Jul;15(7):1308-1321. doi: 10.1016/j.jcmg.2022.03.002. Epub 2022 Mar 16.

Abstract

BACKGROUND

The proprotein convertase subtilisin kexin type-9 inhibitor evolocumab produced coronary atheroma regression in statin-treated patients.

OBJECTIVES

The purpose of this study was to determine the effect of evolocumab on optical coherence tomography (OCT) measures of plaque composition.

METHODS

Patients with a non-ST-segment elevation myocardial infarction were treated with monthly evolocumab 420 mg (n = 80) or placebo (n = 81) for 52 weeks. Patients underwent serial OCT and intravascular ultrasound imaging within a matched arterial segment of a nonculprit vessel. The primary analysis determined the change in the minimum fibrous cap thickness and maximum lipid arc throughout the imaged arterial segment. Additional analyses determined changes in OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were evaluated.

RESULTS

Among treated patients (age 60.5 ± 9.6 years; 28.6% women; low-density lipoprotein cholesterol [LDL-C], 141.3 ± 33.1 mg/dL), 135 had evaluable imaging at follow-up. The evolocumab group achieved lower LDL-C levels (28.1 vs 87.2 mg/dL; P < 0.001). The evolocumab group demonstrated a greater increase in minimum fibrous cap thickness (+42.7 vs +21.5 μm; P = 0.015) and decrease in maximum lipid arc (-57.5 vs. -31.4; P = 0.04) and macrophage index (-3.17 vs -1.45 mm; P = 0.04) throughout the arterial segment. Similar benefits of evolocumab were observed in lipid-rich plaque regions. Greater regression of percent atheroma volume was observed with evolocumab compared with placebo (-2.29% ± 0.47% vs -0.61% ± 0.46%; P = 0.009). The groups did not differ regarding changes in microchannels or calcium.

CONCLUSIONS

The combination of statin and evolocumab after a non-ST-segment elevation myocardial infarction produces favorable changes in coronary atherosclerosis consistent with stabilization and regression. This demonstrates a potential mechanism for the improved clinical outcomes observed achieving very low LDL-C levels following an acute coronary syndrome. (Imaging of Coronary Plaques in Participants Treated With Evolocumab; NCT03570697).

摘要

背景

前蛋白转化酶枯草溶菌素 9 抑制剂依洛尤单抗可使他汀类药物治疗的患者冠状动脉粥样硬化消退。

目的

本研究旨在确定依洛尤单抗对斑块成分的光学相干断层扫描(OCT)测量的影响。

方法

非 ST 段抬高型心肌梗死患者接受每月依洛尤单抗 420mg(n=80)或安慰剂(n=81)治疗 52 周。患者在非罪犯血管的匹配动脉段内进行连续 OCT 和血管内超声成像。主要分析确定整个成像动脉段中最小纤维帽厚度和最大脂质弧的变化。额外的分析确定富含脂质斑块区域和斑块负担的 OCT 特征变化。评估安全性和耐受性。

结果

在接受治疗的患者(年龄 60.5±9.6 岁;28.6%为女性;低密度脂蛋白胆固醇 [LDL-C],141.3±33.1mg/dL)中,有 135 人在随访时有可评估的成像。依洛尤单抗组 LDL-C 水平更低(28.1 与 87.2mg/dL;P<0.001)。依洛尤单抗组最小纤维帽厚度增加更明显(+42.7 与+21.5μm;P=0.015),最大脂质弧减少(-57.5 与-31.4;P=0.04)和巨噬细胞指数降低(-3.17 与-1.45mm;P=0.04),整个动脉段。依洛尤单抗在富含脂质的斑块区域也观察到类似的益处。与安慰剂相比,依洛尤单抗组动脉粥样瘤体积百分比的消退更大(-2.29%±0.47%与-0.61%±0.46%;P=0.009)。两组间微通道或钙的变化无差异。

结论

非 ST 段抬高型心肌梗死后他汀类药物联合依洛尤单抗治疗可使冠状动脉粥样硬化发生有利变化,稳定并消退。这表明在急性冠脉综合征后,实现非常低的 LDL-C 水平时,观察到改善的临床结果可能有一个潜在的机制。(依洛尤单抗治疗患者的冠状动脉斑块成像;NCT03570697)。

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