Effects of alirocumab on endothelial function and coronary atherosclerosis in myocardial infarction: A PACMAN-AMI randomized clinical trial substudy

Atherosclerosis. 2024 May:392:117504. doi: 10.1016/j.atherosclerosis.2024.117504. Epub 2024 Mar 6.

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.

Publication types

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

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized* / pharmacology
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Brachial Artery / diagnostic imaging
  • Brachial Artery / drug effects
  • Brachial Artery / physiopathology
  • Coronary Artery Disease* / complications
  • Coronary Artery Disease* / diagnostic imaging
  • Coronary Artery Disease* / drug therapy
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiopathology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endothelium, Vascular* / drug effects
  • Endothelium, Vascular* / physiopathology
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Male
  • Middle Aged
  • Myocardial Infarction* / complications
  • Myocardial Infarction* / diagnostic imaging
  • Myocardial Infarction* / drug therapy
  • Myocardial Infarction* / physiopathology
  • PCSK9 Inhibitors*
  • Plaque, Atherosclerotic / drug therapy
  • Proprotein Convertase 9
  • Rosuvastatin Calcium* / therapeutic use
  • Spectroscopy, Near-Infrared
  • Time Factors
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Ultrasonography, Interventional*
  • Vasodilation / drug effects

Substances

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

Associated data

  • ClinicalTrials.gov/NCT03067844