Effect of alirocumab on coronary plaque stratified by atherothrombotic risk

Volume 412, January 2026, 120588

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Around 40% of AMI patients were classified as VHR according to the VHR criteria proposed by the ACC/AHA guideline.

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The addition of alirocumab to high-intensity statin therapy showed greater plaque regression in AMI patients without VHR.

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Our findings suggest that intensive LDL-C lowering may offer clinical benefits even in patients without VHR.

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Further research should clarify the impact of atherothrombotic risks on plaque regression and subsequent risk reduction.

AbstractBackground and aims

Previous clinical studies have demonstrated the enhanced cardiovascular benefit of proprotein convertase subtilisin/kexin type 9 inhibition in high-risk patient subsets; however, the mechanisms underlying the greater benefit among patients at high atherothrombotic risk remain largely unknown. We aimed to investigate the effect of alirocumab on coronary plaque regression stratified according to AHA/ACC guideline-defined risk categories among patients with acute myocardial infarction (AMI).

Methods

This was a substudy of the PACMAN-AMI trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in addition to high-intensity statin in AMI patients undergoing percutaneous coronary intervention. Patients underwent serial intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT) in the non-infarct-related arteries at baseline and after 52 weeks. Patients were categorized as very-high risk (VHR) if they had at least 1 prior cardiovascular event or at least 2 high-risk conditions. The key outcome measures were percent atheroma volume (PAV) by IVUS, maximum lipid core burden index within 4 mm (maxLCBI4mm) by NIRS, minimum fibrous cap thickness (FCT) and macrophage angle by OCT.

Results

Among 263 patients available for serial IVUS data, 111 (42.2 %) were classified as VHR. A greater reduction in PAV by alirocumab was observed in the non-VHR group compared with the VHR group (difference in change: 1.8 % [-2.5 to −1.0], P < 0.001 vs. −0.8 % [-1.7 to −0.1], P = 0.068, Pfor interaction = 0.109). Similarly, greater reduction in maxLCBI4mm and macrophage angle was observed in non-VHR vs. VHR patients (−72.8 [-109.3 to −36.4], P < 0.001 vs. −10.1 [-53.4 to 33.2], P = 0.647, Pfor interaction = 0.030, and +21.2 μm [-1.4 to +43.8], P = 0.066 vs. +35.0 μm [+8.3 to +61.8], P = 0.011, Pfor interaction = 0.031, respectively). In contrast, the increase in minimum FCT was more pronounced in the VHR group than the non-VHR group (difference in change: +21.2 μm [-1.4 to +43.8], P = 0.066 vs. +35.0 μm [+8.3 to +61.8], P = 0.011, Pfor interaction = 0.440).

Conclusions

Among AMI patients, the addition of alirocumab to high-intensity statin therapy resulted in greater coronary plaque regression and lipid burden reduction in patients not at VHR. Further investigation is needed to clarify the impact of atherothrombotic risks on plaque regression and subsequent risk reduction in different patient subsets.

Graphical abstractACS = acute coronary syndrome, AMI = acute myocardial infarction, ASCVD = atherosclerotic cardiovascular disease, CABG = coronary artery bypass grafting, CKD = chronic kidney disease, DM = diabetes mellitus, FCT = fibrous cap thickness, FH = familial hypercholesterolemia, HT = hypertension, IVUS = intravascular ultrasound, LCBI = lipid core burden index, LDL-C = low-density lipoprotein cholesterol, MI = myocardial infarction, NIRS = near infrared spectroscopy, OCT = optical coherence tomography, PAD = peripheral artery disease, PAV = percent atheroma volume, PCI = percutaneous coronary intervention, VHR = very high-risk.