Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy

• Published in: Atherosclerosis 2024-05, Vol.392, p.117504, Article 117504
• Main Authors: Rexhaj, Emrush, Bär, Sarah, Soria, Rodrigo, Ueki, Yasushi, Häner, Jonas D., Otsuka, Tatsuhiko, Kavaliauskaite, Raminta, Siontis, George CM, Stortecky, Stefan, Shibutani, Hiroki, Spirk, David, Engstrøm, Thomas, Lang, Irene, Morf, Laura, Ambühl, Maria, Windecker, Stephan, Losdat, Sylvain, Koskinas, Konstantinos C., Räber, Lorenz
• Format: Article
• Language: English
• Subjects: Aged; Alirocumab; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Brachial Artery - diagnostic imaging; Brachial Artery - drug effects; Brachial Artery - physiopathology; Coronary Artery Disease - complications; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - drug therapy; Coronary atherosclerosis; Coronary Vessels - diagnostic imaging; Coronary Vessels - drug effects; Coronary Vessels - physiopathology; Double-Blind Method; Drug Therapy, Combination; Endothelial function; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Female; Flow-mediated dilation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Intracoronary imaging; Male; Middle Aged; Myocardial Infarction - complications; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - drug therapy; Myocardial Infarction - physiopathology; PCSK9 inhibitor; PCSK9 Inhibitors; Plaque, Atherosclerotic - drug therapy; Proprotein Convertase 9; Rosuvastatin Calcium - therapeutic use; Spectroscopy, Near-Infrared; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional; Vasodilation - drug effects
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2024.117504

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