瑞士伯尔尼大学医院Lorenz Räber团队研究了阿莫罗布单抗联合高强度他汀类药物治疗对急性心肌梗死患者冠状动脉粥样硬化的影响。2022年4月3日出版的《美国医学会杂志》发表了这项成果。

易破裂并导致不良心脏事件的冠状动脉斑块具有斑块负荷大、脂质含量高和纤维帽薄的特点。他汀类药物可以阻止冠状动脉粥样硬化的进展；然而，在他汀类药物治疗中添加前蛋白转化酶枯草杆菌素kexin9型抑制剂阿莫罗布单抗对斑块负荷和成分的影响在很大程度上依然未知。

为了通过急性心肌梗死患者的连续多模态冠状动脉内成像，来确定阿莫罗布单抗对冠状动脉粥样硬化的影响，研究组进行了一项双盲、安慰剂对照、随机临床试验，2017年5月9日至2020年10月7日，在欧洲9家学术医院登记了300名接受急性心肌梗死经皮冠状动脉介入治疗的患者。

将患者随机分组，分别接受两周一次的阿莫罗布单抗皮下注射（148例）或安慰剂（152例），除高强度他汀类药物治疗（瑞舒伐他汀，20mg）外，在对罪犯病变进行紧急经皮冠状动脉介入治疗后不到24小时开始，连续治疗52周。

在基线检查时和52周后，研究组对2条非梗死相关冠状动脉连续进行血管内超声（IVUS）、近红外光谱和光学相干断层扫描。主要疗效终点是从基线检查到第52周IVUS衍生的动脉粥样硬化体积百分比的变化。

两个重要的次要终点是从基线检查到第52周，近红外光谱法得出的4mm以内最大脂质核心负荷指数（较高值表示脂质含量较高）和光学相干断层扫描得出的最小纤维帽厚度（较小值表示帽薄、易受损伤的斑块）的变化。

300名患者的平均年龄为58.5岁，56名（18.7%）为女性；平均低密度脂蛋白胆固醇水平为152.4 mg/dL，265名（88.3%）在537条动脉中进行了连续IVUS成像。52周时，阿莫罗布单抗组动脉粥样硬化体积百分比平均降低2.13%，安慰剂组平均增加0.92%，组间差异显著。

阿莫罗布单抗组4mm内的最大脂质核心负荷指数平均降低79.42，安慰剂组平均增加37.60，组间差异显著。阿莫罗布单抗组最小纤维帽厚度平均增加62.67μm，安慰剂组平均增加33.19μm，组间差异显著。阿莫罗布单抗组有70.7%的患者发生不良事件，安慰剂组有72.8%。

研究结果表明，在急性心肌梗死患者中，与安慰剂相比，在高强度他汀类药物治疗中加入两周一次的阿莫罗布单抗，52周后非梗死相关动脉的冠状动脉斑块消退显著增加。仍需进一步研究来了解阿莫罗布单抗是否能改善该人群的临床预后。

附：英文原文

Title: Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial

Author: Lorenz Rber, Yasushi Ueki, Tatsuhiko Otsuka, Sylvain Losdat, Jonas D. Hner, Jacob Lonborg, Gregor Fahrni, Juan F. Iglesias, Robert-Jan van Geuns, Anna S. Ondracek, Maria D. Radu Juul Jensen, Christian Zanchin, Stefan Stortecky, David Spirk, George C. M. Siontis, Lanja Saleh, Christian M. Matter, Joost Daemen, Franois Mach, Dik Heg, Stephan Windecker, Thomas Engstrm, Irene M. Lang, Konstantinos C. Koskinas, PACMAN-AMI collaborators, Maria Ambühl, Sarah Br, André Frenk, Laura U. Morf, Andrea Inderkum, Stefanie Leuthard, Raminta Kavaliauskaite, Emrush Rexhaj, Hiroki Shibutani, Vera R. Mitter, Christoph Kaiser, Manuel Mayr, Franz R. Eberli, Crochan J. OSullivan, Christian Templin, Arnold von Eckardstein, Art Ghandilyan, Ravindra Pawar, Hans Jonker, Thomas Hofbauer, Georg Goliasch, Lia Bang, Rikke Srensen, Maria N. Tovar Forero, Sophie Degrauwe, Tim Ten Cate

Issue&Volume: 2022-04-03

Abstract:

Importance  Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown.

Objective  To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction.

Design, Setting, and Participants  The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals.

Interventions  Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n=148) or placebo (n=152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg).

Main Outcomes and Measures  Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non–infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy–derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography–derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52.

Results  Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, mean change in percent atheroma volume was 2.13% with alirocumab vs 0.92% with placebo (difference, 1.21% [95% CI, 1.78% to 0.65%], P<.001). Mean change in maximum lipid core burden index within 4 mm was 79.42 with alirocumab vs 37.60 with placebo (difference, 41.24 [95% CI, 70.71 to 11.77]; P=.006). Mean change in minimal fibrous cap thickness was 62.67 μm with alirocumab vs 33.19 μm with placebo (difference, 29.65 μm [95% CI, 11.75-47.55]; P=.001). Adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving placebo.

Conclusions and Relevance  Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non–infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population.

DOI: 10.1001/jama.2022.5218

Source: https://jamanetwork.com/journals/jama/fullarticle/2790913