TY - JOUR
T1 - Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction
T2 - A PACMAN-AMI randomized clinical trial substudy
AU - Rexhaj, Emrush
AU - Bär, Sarah
AU - Soria, Rodrigo
AU - Ueki, Yasushi
AU - Häner, Jonas D
AU - Otsuka, Tatsuhiko
AU - Kavaliauskaite, Raminta
AU - Siontis, George Cm
AU - Stortecky, Stefan
AU - Shibutani, Hiroki
AU - Spirk, David
AU - Engstrøm, Thomas
AU - Lang, Irene
AU - Morf, Laura
AU - Ambühl, Maria
AU - Windecker, Stephan
AU - Losdat, Sylvain
AU - Koskinas, Konstantinos C
AU - Räber, Lorenz
AU - PACMAN-AMI Investigators
N1 - Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2024/5
Y1 - 2024/5
N2 - BACKGROUND AND AIMS: 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).METHODS: 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.RESULTS: 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).CONCLUSIONS: 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.
AB - BACKGROUND AND AIMS: 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).METHODS: 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.RESULTS: 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).CONCLUSIONS: 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.
KW - Alirocumab
KW - Coronary atherosclerosis
KW - Endothelial function
KW - Flow-mediated dilation
KW - Intracoronary imaging
KW - PCSK9 inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85188245285&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2024.117504
DO - 10.1016/j.atherosclerosis.2024.117504
M3 - Journal article
C2 - 38513436
SN - 0021-9150
VL - 392
JO - Atherosclerosis
JF - Atherosclerosis
M1 - 117504
ER -