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

Am Heart J. 2021 Aug:238:33-44. doi: 10.1016/j.ahj.2021.04.006. Epub 2021 May 2.

Abstract

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 (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI.

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 maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Cholesterol, LDL
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / drug therapy*
  • 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
  • Plaque, Atherosclerotic / drug therapy*
  • Proprotein Convertase 9 / immunology*
  • Research Design
  • Rosuvastatin Calcium / administration & dosage
  • ST Elevation Myocardial Infarction / complications
  • Spectroscopy, Near-Infrared
  • Tomography, Optical Coherence

Substances

  • Antibodies, Monoclonal, Humanized
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Placebos
  • Rosuvastatin Calcium
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • alirocumab

Associated data

  • ClinicalTrials.gov/NCT03067844