Oxidized phospholipid dynamics in the early post-infarction period: Effects of PCSK9 inhibition with evolocumab

Background and aims: The peri- and early post-infarction period carries an increased risk of recurrent ischemic events. Oxidized phospholipids (OxPLs) are pro-inflammatory and contribute to plaque instability and thrombosis. This study aimed to: (1) assess changes, during the early post-MI period in OxPL-apo(a) and OxPL-apoB, (2) evaluate the effect of PCSK9 inhibition on these changes, and (3) explore their relationships with the changes in Lp(a) and LDL-C. Methods: Ninety-six participants with NSTEMI or STEMI were randomized to receive placebo (n = 48) or 420 mg subcutaneous evolocumab (n = 48) within 24 h of admission. OxPL-apo(a), OxPL-apoB, Lp(a), and LDL-C levels were measured at baseline and 30 days post-MI. Results: In the placebo group, OxPL-apo(a) increased from 52.6 [19.3, 106.5] nmol/L at baseline to 61.7 [31.5, 116.9] nmol/L at 30 days (p = 0.014), and OxPL-apoB rose from 6.7 [3.1, 21] nmol/L to 8.8 [3.7, 23] nmol/L (p = 0.0045). In contrast, no significant changes were observed for OxPL-apo(a) (p = 0.17) or OxPL-apoB (p = 0.058) in the evolocumab group. OxPL-apo(a) correlated strongly with Lp(a) at baseline (r = 0.93, p < 0.001) and 30 days (r = 0.94, p < 0.001), and OxPL-apoB correlated similarly (baseline: r = 0.92, p < 0.001; 30 days: r = 0.93, p < 0.001). No correlation was observed between OxPLs and LDL-C. Conclusion: OxPL-apo(a) and OxPL-apoB levels were strongly correlated with Lp(a) and increased during the early post-infarction period. This increase was prevented by in-hospital administration of a PCSK9 inhibitor. These findings provide new insights into early changes in OxPLs following acute MI and suggest a protective role for PCSK9 inhibition during this critical period.