Although elevated oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) levels predicted major adverse cardiovascular events (MACE) in patients with a recent acute coronary syndrome (ACS) receiving optimized statin treatment, alirocumab significantly attenuated the risk. And when lipoprotein (a) [Lp(a)] levels were low, elevated OxPL-apoB independently predicted MACE, according to a post hoc analysis of the ODYSSEY OUTCOMES trial, published Dec. 1 in Circulation.

In the ODYSSEY OUTCOMES trial, OxPL-apoB levels and Lp(a) were measured in 11,630 patients (5,804 randomized to alirocumab and 5,826 to placebo) before and 5,185 patients (2,589 randomized to alirocumab and 2,596 to placebo) four months after randomization. Median age was 58 years and 24% were women.

In the current analysis, Sotirios Tsimikas, MD, FACC, et al., evaluated associations between log2-transformed OxPL-apoB and Lp(a) with MACE, as well as interactions between these biomarkers and treatment with alirocumab, a PCSK9 inhibitor.

The primary efficacy endpoint of the trial and current analysis was time to first occurrence of a MACE, defined as death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.

Results showed that alirocumab reduced median placebo-adjusted OxPL-apoB by 13.0% and Lp(a) by 26.2% (both p<0.0001). When baseline OxPL-apoB was doubled in the placebo group, it was associated with a hazard ratio of 1.081 (p=0.0034) for MACE. However, when Lp(a) was added to the model, the relationship of OxPL-apoB was not significant. Neither OxPL-apoB nor Lp(a) remained significantly associated with MACE in the alirocumab group.

In other findings, a significant three-way interaction was present among continuous log2 OxPL-apoB, Lp(a) stratified at the median, and treatment group on MACE (p for interaction=0.0023) so that, in the placebo group, increasing OxPL-apoB was associated with a higher risk of MACE when Lp(a) was below, but not above, the median concentration.

Notably, OxPL-apoB was not predictive of MACE risk regardless of Lp(a) concentration in the alirocumab group, indicating that alirocumab attenuated OxPL-apoB–associated risk.

Tsimikas and colleagues write that "this analysis provides novel observations about the interplay of OxPL-apoB and Lp(a) as biomarkers of cardiovascular risk" in this patient population and "suggest that in post-ACS settings with optimized statin therapy, OxPL-apoB may provide additional prognostic information in patients with Lp(a) in the normal range."