Effect of alirocumab on coronary plaque stratified by atherothrombotic risk

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).

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 (maxLCBI_4mm) by NIRS, minimum fibrous cap thickness (FCT) and macrophage angle by OCT.

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, P_{for interaction} = 0.109). Similarly, greater reduction in maxLCBI_4mm 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, P_{for 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, P_{for 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, P_{for interaction} = 0.440).

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.