Lesion-level effects of LDL-C lowering therapy in patients with AMI. The PACMAN-AMI lesion-level analysis

Abstract

Background. Previous intracoronary imaging studies investigated atherosclerotic changes induced by lipid-lowering therapy in extensive coronary segments, irrespective of baseline disease burden (vessel-level approach). The effects of lipid-lowering treatment on coronary lesions with advanced atherosclerosis and at presumably higher risk for future events remains unknown. Methods. The PACMAN-AMI trial randomized patients with acute myocardial infarction to receive alirocumab or placebo in addition to high-intensity statin therapy. In this pre-specified lesion-level analysis, nonculprit lesions were identified as segments with plaque burden ≥40% defined by intravascular ultrasound (IVUS). IVUS, near-infrared spectroscopy, and optical coherence tomography images at baseline and 52-week follow-up were manually matched, and changes in lesion-level imaging outcomes including high-risk plaque characteristics and phenotypes were assessed. Results. Overall, 591 lesions with available serial imaging were included: 287 lesions in 118 patients (214 vessels) in the alirocumab group and 304 lesions in 127 patients (239 vessels) in the placebo group. 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<0.001). 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<0.001). MLA increased by 0.15 mm2 with alirocumab and decreased by 0.07 mm2 in the placebo group (difference, +0.21, 0.01 to 0.41, p=0.036), whereas arterial remodeling (change in vessel area) was similar between groups (-0.73±1.61 mm2 in alirocumab vs -0.63±1.31 mm2 in placebo group, p=0.482). Among lipid-rich lesions, 61.8% of those in alirocumab arm and 41.8% of those in placebo arm showed a less lipid-rich plaque phenotype at follow-up (p=0.03). Among lesions with thin-cap fibroatheroma <65 μm at baseline, 30.8% of those in alirocumab arm and 8.1% of those in placebo arm showed a fibrous/fibrocalcific plaque phenotype at follow-up (p=0.02). Conclusions. At lesion-level, very intensive lipid-lowering therapy induced substantially greater PAV regression than described in previous vessel-level analyses. Compared to statin therapy alone, alirocumab treatment was associated with greater enlargement of the lesion MLA, similar negative arterial remodeling, and more frequent transition of high-risk plaque phenotypes into more stable, less lipid-rich plaque phenotypes