Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy
- PMID: 38513436
- DOI: 10.1016/j.atherosclerosis.2024.117504
Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy
Abstract
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.
Trial registration: ClinicalTrials.gov NCT03067844.
Keywords: Alirocumab; Coronary atherosclerosis; Endothelial function; Flow-mediated dilation; Intracoronary imaging; PCSK9 inhibitor.
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Rexhaj reports research grants from the Swiss National Science Foundation, Innosuisse-Suisse Innovation Agency, Swiss Heart Foundation, Mach-Gaensslen Stiftung Schweiz; speaker fees to institution from Servier; consulting fees to institution from Boehringer Ingelheim, outside the submitted work. Dr. Bär reports research grants to the institution from Medis Medical Imaging Systems, Abbott, Bangerter-Rhyner Stiftung; and personal research grants from the Swiss National Science Foundation, and the University of Turku, Finland, outside the submitted work. Prof. Ueki reports grants from Astellas Pharma, personal fees from Abbott Vascular, Amgen, Bayer, Daiichi Sankyo, Kowa, NIPRO, and Novartis, outside the submitted work. Dr. Siontis reports personal fees from Abbott Vascular, outside the submitted work. Prof. Stortecky reports research grants to the institution from Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific and speaker fees from Boston Scientific, outside the submitted work. Prof. Spirk reports personal fees from Sanofi-Aventis (Suisse), outside the submitted work. Prof. Engstrøm reports speaker fees from Abbott, outside the submitted work. Prof. Lang reports grants and personal fees from Janssen, and AOPOrphan; personal fees from MSD; and grants from Neutrolis, outside the submitted work. Prof. Windecker reports research, travel or educational grants to the institution from Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi-Aventis, Servier, Sinomed, Terumo, Vifor, V-Wave. Prof. Windecker serves as advisory board member and/or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, Boston Scientific, Biotronik, Bristol-Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave and Xeltis with payments to the institution but no personal payments. He is also member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr. Koskinas reports grants from Sanofi, Regeneron, and Infraredx during the conduct of the PACMAN-AMI main trial and personal fees from Amgen and Daiichi Sankyo, outside the submitted work. Dr. Losdat is employed by CTU Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations. In particular, pharmaceutical and medical device companies provide direct funding to some of these studies. For an up-to-date list of CTU Bern's conflicts of interest: http://www.ctu.unibe.ch/research/declaration_of_interest/index_eng.html. Prof. Räber reports research grants to the institution from Abbott Vascular, Biotronik, Boston Scientific, Heartflow, Sanofi, Regeneron, Medis Medical Imaging Systems, Bangerter-Rhyner Stiftung, Swiss National Science foundation, Swiss Heart Foundation; speaker or consultation fees by Abbott Vascular, Amgen, AstraZeneca, Canon, Medtronic, Novo Nordisk, Occlutech, Sanofi, Vifor, outside the submitted work. All other authors report no conflicts of interest.
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