Oxidised phospholipids on apoB predict MACE after ACS and alirocumab abolishes the relation: ODYSSEY OUTCOMES (Tsimikas et al., Circulation 2025)

Original title: Oxidized Phospholipids, Lipoprotein(a), and Cardiovascular Outcomes After Acute Coronary Syndrome

Circulation · 16 December 2025 · 6

Tsimikas S, Szarek M, Cobbaert CM, Romijn F, Jukema JW, Bhatt DL, Bittner VA, Diaz R, Fazio S, Garon G, Yuan C, Gong XM et al.

In 11,630 ODYSSEY OUTCOMES participants, a doubling of baseline OxPL-apoB carried a hazard ratio for MACE of 1.08 on placebo, which lost significance once Lp(a) entered the model, and there was a three-way interaction: OxPL-apoB predicted events when Lp(a) was below the median, not above; alirocumab lowered OxPL-apoB by 13 percent and Lp(a) by 26 percent, and neither predicted MACE on treatment. Leiden (Cobbaert) among the authors.

Original abstract

Background: Oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) reflect pro-inflammatory properties of Lp(a) (lipoprotein(a)). The effect of OxPL-apoB on major adverse cardiovascular events (MACE) in patients with acute coronary syndrome in recent the era is not known.

Methods: OxPL-apoB levels and Lp(a) were measured in 11 630 participants before and 5185 participants 4 months after randomization to alirocumab or placebo in the ODYSSEY OUTCOMES trial. Proportional hazards models adjusted for baseline covariates evaluated associations between log2-transformed OxPL-apoB and Lp(a) with MACEs. Interactions between the 2 biomarkers and treatment were also evaluated.

Results: Participants were followed for a median 2.9 years; the median age was 58 years, and 23.9% were female. Alirocumab reduced median placebo-adjusted OxPL-apoB by 13.0% and Lp(a) by 26.2% (both P<0.0001). In the placebo group, a doubling of baseline OxPL-apoB was associated with a hazard ratio (HR) of 1.081 (95% CI, 1.026-1.139; P=0.0034) for MACEs. Addition of Lp(a) to the model relegated the relationship of OxPL-apoB insignificant. In the alirocumab group, neither OxPL-apoB nor Lp(a) remained significantly associated with MACEs. A significant 3-way interaction was present among continuous log2 OxPL-apoB, Lp(a) stratified at the median, and treatment group on MACEs (Pinteraction=0.0023) so that, in the placebo group, increasing OxPL-apoB was associated with higher risk of MACEs when Lp(a) was below the median concentration but not above. In the alirocumab group, OxPL-apoB was not related to MACE risk irrespective of Lp(a) concentration.

Conclusions: In patients with recent acute coronary syndrome receiving optimized statin treatment, elevated OxPL-apoB levels predicted MACEs, a relationship abrogated by alirocumab. The interaction of OxPL-apoB and Lp(a) in the placebo group indicates that OxPL-apoB independently predicts MACEs when Lp(a) levels are relatively low.

Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT001747 and NCT01663402.

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