Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study-Rationale and design of the PACMAN-AMI trial.
Antibodies, Monoclonal, Humanized
/ administration & dosage
Cholesterol, LDL
Coronary Artery Disease
/ diagnostic imaging
Double-Blind Method
Drug Administration Schedule
Endosonography
Europe
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ therapeutic use
Myocardial Infarction
/ complications
Non-ST Elevated Myocardial Infarction
/ complications
Placebos
/ administration & dosage
Plaque, Atherosclerotic
/ diagnostic imaging
Proprotein Convertase 9
/ immunology
Research Design
Rosuvastatin Calcium
/ administration & dosage
ST Elevation Myocardial Infarction
/ complications
Spectroscopy, Near-Infrared
Tomography, Optical Coherence
Journal
American heart journal
ISSN: 1097-6744
Titre abrégé: Am Heart J
Pays: United States
ID NLM: 0370465
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
16
11
2020
accepted:
26
04
2021
pubmed:
6
5
2021
medline:
27
8
2021
entrez:
5
5
2021
Statut:
ppublish
Résumé
The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. NCT03067844.
Sections du résumé
BACKGROUND
The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown.
AIMS
To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI
METHODS
In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI
SUMMARY
The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI.
CLINICAL TRIAL REGISTRATION
NCT03067844.
Identifiants
pubmed: 33951415
pii: S0002-8703(21)00108-3
doi: 10.1016/j.ahj.2021.04.006
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Cholesterol, LDL
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Placebos
0
Rosuvastatin Calcium
83MVU38M7Q
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
alirocumab
PP0SHH6V16
Banques de données
ClinicalTrials.gov
['NCT03067844']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
33-44Informations de copyright
Copyright © 2021. Published by Elsevier Inc.