Lesion-level changes induced by low-density lipoprotein cholesterol lowering therapy in patients with acute myocardial infarction: the pre-specified PACMAN-AMI lesion-level analysis
Authors: Biccire F G , Kakizaki R , Losdat S , Ueki Y , Shibutani H , Haner J , Spitzer E , Iglesias J , Van Jeuns R J , Spirk D , Daemen J , Engstrom T , Lang I , Koskinas K C , Raber L 
Published: October 2024

Abstract

Background
Previous intracoronary imaging studies investigated atherosclerotic changes induced by lipid-lowering therapy in extensive coronary segments, based on anatomical landmarks and irrespective of the baseline atheroma burden. The effects of lipid-lowering therapy focusing on coronary lesions with advanced atherosclerotic features and at presumably higher risk for future events remains largely unknown.

Purpose
To provide a lesion-level analysis reporting changes in high-risk atherosclerotic features and plaque phenotypes induced by alirocumab versus placebo in addition to high-intensity statin therapy in nonculprit coronary lesions of patients admitted with acute myocardial infarction (AMI).

Methods
In this pre-specified lesion-level analysis of the PACMAN-AMI trial, coronary lesions were identified as segments with plaque burden ≥40% defined by intravascular ultrasound (IVUS). IVUS, near-infrared spectroscopy (NIRS) and optical coherence tomography (OCT) images at baseline and 52-week follow-up were manually matched and lesion-level imaging outcome measures were calculated by analysts blinded to treatment allocation and patient clinical data. The evolution of high-risk plaque phenotypes as defined by each imaging modality (IVUS-defined plaque burden ≥70%, NIRS-defined maximum LCBI 4 mm ≥400, OCT-defined thin-cap fibroatheroma &lt;65µm) was investigated.

Results
Overall, 591 lesions with available baseline and follow-up imaging were included. Of these, 287 were identified in 118 patients (214 vessels) in the alirocumab arm, and 304 lesions were identified in 127 patients (239 vessels) in the placebo arm. At lesion-level, mean change in percent atheroma volume (PAV) by IVUS was -4.86% with alirocumab vs -2.78% with placebo (difference, -2.02 [-3.00 to -1.05], p&lt;.001), substantially greater than that at vessel-level (Figure 1). At the minimum lumen area (MLA) site, mean change in PAV was -10.14% with alirocumab vs -6.70% with placebo (difference, -3.36 (-4.98 to -1.75, p&lt;0.001). MLA increased by 0.15 mm2 with alirocumab and decreased by 0.07 mm2 in the placebo arm (difference, +0.21, 0.01 to 0.41, p=0.036), whereas arterial remodeling was similar between arms (-0.73±1.61 in alirocumab vs -0.63±1.31 in placebo group, p=0.482). Among lesions with high-risk plaque phenotypes at baseline, those in the alirocumab arm more frequently showed a more stable and less lipid-rich plaque phenotype at follow-up than those in the placebo arm (Figure 2).

Conclusions
At lesion-level, intense lipid-lowering therapy with alirocumab in addition to high-intensity statin therapy induced extensive PAV regression, substantially greater than described in previous vessel-level analyses. Compared to statin therapy alone, alirocumab treatment was associated with a greater enlargement of the lesion MLA, similar negative arterial remodeling, and a more frequent transition of high-risk plaque phenotypes into more stable, less lipid-rich plaque phenotypes.Figure 1.Figure 2