Background <p>Oxidative modification of apolipoprotein B-100 (apoB) containing particles and subsequent immune responses contribute to the pathogenesis of atherosclerosis. Circulating IgG and IgM apoB-containing immune complexes (apoB-IC) and autoantibodies to a malondialdehyde mimotope (anti-MDA-mimotope) serve as biomarkers of oxidative stress and immune activation in atherosclerotic cardiovascular disease. Elevated lipoprotein(a) [Lp(a)] is associated with increased oxidative burden and immune activation.</p> Purpose <p>To investigate the effect of lipid-lowering medications on IgG and IgM apoB-IC and IgG and IgM autoantibodies to an MDA-mimotope in individuals with elevated lipoprotein(a) [Lp(a)] concentrations.</p> Methods <p>In this prospective study, patients (<i>n</i> = 70) with Lp(a) levels ≥ 75&#xa0;nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (<i>n</i> = 28), ezetimibe added to high-intensity statin (<i>n</i> = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (<i>n</i> = 11). IgG and IgM apoB-IC and IgG and IgM anti-MDA-mimotope were measured at baseline and 3&#xa0;months after treatment initiation.</p> Results <p>Patients had a mean age of 51 ± 15&#xa0;years and 40% were male. Significant reductions in IgG apoB-IC levels were observed following treatment with high-intensity statins, add-on ezetimibe and add-on PCSK9i (by 18.3%, 17.5% and 25.5%, respectively, all <i>p</i> &lt; 0.05). No significant changes in IgM apoB-IC, or IgG and IgM anti-MDA-mimotope levels were observed in any treatment group.</p> Conclusions <p>In individuals with Lp(a) levels ≥ 75&#xa0;nmol/L, high-intensity statins, add-on ezetimibe and add-on PCSK9i reduced IgG apoB-IC but did not affect IgM apoB-IC, or IgG and IgM anti-MDA-mimotope levels. The clinical significance of these findings warrants further investigation.</p> Graphical Abstract <p></p>