Atherosclerosis is a disorder in which, in addition to high cholesterol levels, several plasma factors play a significant role in its development. Among these cytokines and molecules are interleukin 6 (IL-6), interleukin 18 (IL-18), tumor necrosis factor α (TNF-α), metalloproteinase 2 (MMP-2), and metalloproteinase 9 (MMP-9), all of which may contribute to the stabilization of atherosclerotic plaque. The purpose of this study was to determine the effect of advanced lipid-lowering therapy on the levels of these determinants by utilizing proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors in patients with verified high-risk atherosclerotic plaque. Methods: The study involved patients with dyslipidemia who had the presence of unstable atherosclerotic plaque verified by ultrasonography and who were eligible to begin alirocumab treatment. The levels of IL-6, IL, 18, TNF-α, and MMPs were determined in this group before and after three months of therapy. After treatment, a statistically significant decrease in concentrations of Il-18, Il-6, TNF-α (p < 0.001) and MMP-2 (p < 0.05) was observed. Additionally, we observed that the concentrations of these markers were significantly higher in the group of patients prior to initiating therapy than in the control group. Our study’s results suggest that PCSK-9 inhibitor therapy significantly reduces the concentration of factors influencing the stability of atherosclerotic plaque, which may explain their essential importance in reducing cardiovascular risk in patients receiving this treatment.