Department of Cardiology, Bern University Hospital Inselspital, Freiburgstrasse 18, 3010, Bern, Switzerland.
Institute of Pharmacology, Bern University Hospital and University of Bern, Freiburgstrasse 18, 3010, Bern, Switzerland; Sanofi, Suurstofi 2, 6343, Risch-Rotkreuz, Switzerland.
Atherosclerosis. 2024 May;392:117504. doi: 10.1016/j.atherosclerosis.2024.117504. Epub 2024 Mar 6.
The effects of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on endothelial function as assessed by flow-mediated dilation (FMD) in patients with acute myocardial infarction (AMI) are unknown. Therefore, we aimed to investigate the effects of the PCSK9 inhibitor alirocumab added to high-intensity statin on FMD, and its association with coronary atherosclerosis in non-infarct related arteries using intracoronary intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT).
This was a pre-specified substudy among patients recruited at Bern University Hospital, Switzerland, for the randomized-controlled, double-blind, PACMAN-AMI trial, which compared the effects of biweekly alirocumab 150 mg vs. placebo added to rosuvastatin. Brachial artery FMD was measured at 4 and 52 weeks, and intracoronary imaging at baseline and 52 weeks.
139/173 patients completed the substudy. There was no difference in FMD at 52 weeks in the alirocumab (n = 68, 5.44 ± 2.24%) versus placebo (n = 71, 5.45 ± 2.19%) group (difference = -0.21%, 95% CI -0.77 to 0.35, p = 0.47). FMD improved throughout 52 weeks in both groups similarly (p < 0.001). There was a significant association between 4 weeks FMD and baseline plaque burden (IVUS) (n = 139, slope = -1.00, p = 0.006), but not with lipid pool (NIRS) (n = 139, slope = -7.36, p = 0.32), or fibrous cap thickness (OCT) (n = 81, slope = -1.57, p = 0.62).
Among patients with AMI, the addition of alirocumab did not result in further improvement of FMD as compared to 52 weeks secondary preventative medical therapy including high-intensity statin therapy. FMD was significantly associated with coronary plaque burden at baseline, but not with lipid pool or fibrous cap thickness.
目前尚不清楚蛋白水解酶枯草溶菌素 9（PCSK9）抑制剂对急性心肌梗死（AMI）患者的血流介导扩张（FMD）的内皮功能的影响。因此，我们旨在研究在非梗塞相关动脉中，与高强度他汀类药物联合应用的 PCSK9 抑制剂阿利西尤单抗对 FMD 的影响，并使用血管内超声（IVUS）、近红外光谱（NIRS）和光学相干断层扫描（OCT）研究其与冠状动脉粥样硬化的关系。
这是在瑞士伯尔尼大学医院参与随机、双盲、PACMAN-AMI 试验的患者中进行的一项预先指定的亚研究，该试验比较了每两周给予 150mg 阿利西尤单抗与安慰剂联合瑞舒伐他汀的效果。在第 4 周和第 52 周测量肱动脉 FMD，并在基线和第 52 周进行冠状动脉成像。
139/173 例患者完成了亚研究。在阿利西尤单抗组（n=68，5.44±2.24%）和安慰剂组（n=71，5.45±2.19%）中，52 周时 FMD 无差异（差异=-0.21%，95%CI-0.77 至 0.35，p=0.47）。两组 FMD 在 52 周内均持续改善（p<0.001）。4 周时的 FMD 与基线时的斑块负荷（IVUS）显著相关（n=139，斜率=-1.00，p=0.006），但与脂质池（NIRS）（n=139，斜率=-7.36，p=0.32）或纤维帽厚度（OCT）（n=81，斜率=-1.57，p=0.62）无显著相关性。
在 AMI 患者中，与包括高强度他汀类药物治疗在内的二级预防医学治疗相比，加用阿利西尤单抗并未进一步改善 FMD。FMD 与基线时的冠状动脉斑块负荷显著相关，但与脂质池或纤维帽厚度无关。
