Statins and ezetimibe raise oxidized phospholipids on Lp(a) even as PCSK9 inhibitors leave them unchanged, 70-patient study finds (Atheroscler Plus 2025)

Original title: Effect of lipid-lowering medications on oxidized phospholipids in individuals with elevated LIPOPROTEIN(a)

Atheroscler Plus · 1 September 2025 · 6

Koutsogianni AD, Barkas F, Tellis C, Tselepis A, Liamis G, Tsimikas S, Liberopoulos E

This prospective study followed 70 patients with Lp(a) of 75 nmol/L or above (mean age 51 ± 15 years, 40% male, 39% with familial hypercholesterolaemia) for 3 months across three guideline-based treatment regimens: high-intensity statin monotherapy (n = 28), statin plus ezetimibe (n = 31), and statin plus ezetimibe plus a PCSK9 inhibitor (n = 11), measuring oxidised phospholipids (OxPL) bound to apoB, apo(a) and plasminogen. Lp(a) itself did not change significantly with statin or statin-plus-ezetimibe, but fell significantly with add-on PCSK9 inhibitor. Counterintuitively, OxPL-apoB and OxPL-apo(a) significantly increased, while OxPL-PLG (which extends time to fibrinolysis) significantly decreased, with both statin monotherapy and statin-plus-ezetimibe, whereas PCSK9 inhibitor add-on produced no significant change in any OxPL measure. The authors flag these divergent effects on oxidised phospholipid biology, independent of and sometimes opposite to the drugs' effect on Lp(a) concentration itself, as needing further clinical exploration.

Original abstract

Background/Introduction: Oxidized phospholipids (OxPLs) are bound to apolipoprotein B-100 (OxPL-apoB) and apolipoprotein(a) [OxPL-apo(a)] and are present freely within the phospholipid shell of apoB-containing lipoproteins. OxPLs have been linked with the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPLs carried on plasminogen (OxPL-PLG) may extend the time to fibrinolysis.

Purpose: To evaluate the effect of lipid-lowering medications on OxPLs levels in individuals with elevated Lp(a) concentrations.

Methods: In this prospective study, patients (n = 70) with Lp(a) levels ≥75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n = 28), ezetimibe added to high-intensity statin (n = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n = 11). Follow-up duration was 3 months.

Results: Patients had a mean age of 51 ± 15 years, 40 % were male, 39 % were diagnosed with familial hypercholesterolemia, 16 % had atherosclerotic cardiovascular disease, and 36 %, 33 % and 15 % were at very high, high, and moderate cardiovascular risk, respectively. Lp(a) levels did not change significantly with high-intensity statin and add-on ezetimibe but significantly decreased with add-on PCSK9i treatment. OxPL-apoB and OxPL-apo(a) significantly increased, while OxPL-PLG significantly decreased with both high-intensity statin and add-on ezetimibe. Add-on PCSK9i treatment was associated with no significant changes in OxPL-apoB, OxPL-apo(a) and OxPL-PLG levels.

Conclusions: Among patients with elevated Lp(a), both high-intensity statin and add-on ezetimibe significantly increased OxPL-apoB and OxPL-apo(a) levels, while significantly decreased OxPL-PLG levels. Add-on PCSK9i had no significant effect on OxPLs levels. The clinical implications of these findings should be further explored.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.