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

Abstract

BackgroundThe 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. AimsTo 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 4 mm ) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. MethodsIn this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-STelevation 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 4 mm , and OCT-derived minimal FCT, will be assessed 52 weeks post randomization.

Assessment of Trimetazidine Treatment in Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention

“…Statins are recommended in patients with AMI, unless there are contraindications, according to the guidelines for the management of acute myocardial infarction [ 18 , 21 , 22 ]. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies were added to statins for reducing LDL-C when statins could not decrease LDL-C effectively [ 32 , 33 ]. However, statins may have adverse effects on skeletal muscle [ 34 ] and renal function and cause increases in liver enzymes susceptibility to type 2 diabetes mellitus [ 35 , 36 ].…”

Effect of Alirocumab on Coronary Plaque in Patients With Coronary Artery Disease Assessed by Optical Coherence Tomography

“…Furthermore, it is well acknowledged that OCT-based thin-cap fibroatheroma is associated with the presence of high-risk features evaluated by other imaging modalities such as virtual histology intravascular ultrasound [28], all of which have a strong link to future adverse clinical events [22,29]. Therefore, to date the thickening of the fibrous cap has been considered as the representation of coronary plaque stabilization [30][31][32][33].…”

Vulnerable Plaque in Patients with Acute Coronary Syndrome: Identification, Importance, and Management

“…107 However, serial plaque compositions assessed by virtual histology IVUS were similar between evolocumab and placebo groups. 107 An ongoing multicenter, double-blind, placebo-controlled trial, PACMAN-AMI, will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics by serial assessment with intra-coronary multimodalities including IVUS, NIRS, and OCT. 108…”