Evolocumab stabilises coronary plaque more effectively in ACS patients with high Lp(a) than low, HUYGENS trial secondary analysis of OCT imaging finds (Eur J Prev Cardiol 2025)

Original title: Impact of evolocumab on plaque phenotypic changes in patients with acute coronary syndrome and elevated lipoprotein(a) levels: a HUYGENS secondary analysis

Eur J Prev Cardiol · 8 April 2025 · 8

Di Giovanni G, Fujino M, Kataoka Y, Butters J, Hucko T, Puri R, Nissen SE, Nelson AJ, Psaltis PJ, Nicholls SJ

This post-hoc analysis of the HUYGENS trial (NCT03570697) used serial optical coherence tomography to compare plaque changes with evolocumab 420 mg versus placebo over 50 weeks in acute coronary syndrome patients, stratified by baseline Lp(a) below 125 nmol/L (n = 71) or at/above it (n = 46). In the high-Lp(a) group, evolocumab produced greater LDL-C and Lp(a) reductions than placebo, and larger increases in minimum fibrous cap thickness (+51.6 vs. +12.4 micrometres, P < 0.001) and larger reductions in lipid arc (-60.9 vs. -9.1 degrees, P = 0.008) than placebo. In the low-Lp(a) group, evolocumab also lowered LDL-C and Lp(a) more than placebo, but produced no significant difference in fibrous cap thickness (P = 0.21) or lipid arc change (P = 0.18) versus placebo. Baseline Lp(a) significantly interacted with evolocumab's effect on fibrous cap thickness (interaction P = 0.04). The authors conclude evolocumab's plaque-stabilising advantage over statin monotherapy is more pronounced in patients with higher Lp(a), suggesting Lp(a) could help identify who benefits most from intensive lipid-lowering therapy.

Original abstract

Aims: The proprotein convertase subtilisin/kexin Type 9 inhibitor, evolocumab, promoted plaque stabilization on serial imaging in patients following an acute coronary syndrome. The impact of evolocumab in patients with varying lipoprotein(a) [Lp(a)] levels is unknown.

Methods And Results: Serial optical coherence tomography imaging was performed to evaluate changes in plaque composition in response to treatment with evolocumab 420 mg or placebo for 50 weeks. The current post hoc analysis compared demographics, biochemistry, and plaque imaging changes in those with baseline Lp(a) levels <125 (n = 71) and ≥125 nmol/L (n = 46). Among those with high Lp(a) levels, evolocumab treatment produced lower levels of LDL cholesterol (LDL-C) (21.7 ± 10.3 vs. 94.5 ± 22.9 mg/dL; P < 0.001) and Lp(a) [156.0 (136.0, 187.0) vs. 204.0 (170.5, 290.5) nmol/L; P = 0.007], compared with placebo. Changes in minimum fibrous cap thickness (FCT) (+51.6 ± 40.9 vs. +12.4 ± 23.9 μm; P < 0.001) and lipid arc (-60.9 ± 56.5° vs. -9.1 ± 70.8°; P = 0.008) were greater in the high Lp(a) group with evolocumab compared with placebo. Among patients with low Lp(a) levels, evolocumab produced lower levels of LDL-C (23.3 ± 34.9 vs. 82.9 ± 46.5 mg/dL; P < 0.001) and Lp(a) [11.5 (5.8, 23.8) vs. 25.0 (13.5, 41.0) nmol/L; P = 0.01] compared with placebo, but no differences were observed between groups in changes in minimum FCT (+45.9 ± 37.8 vs. +34.7 ± 36.0 μm; P = 0.21) and lipid arc (-59.9 ± 50.1° vs. -44.5 ± 46.1°; P = 0.18). Baseline Lp(a) levels significantly interacted with the impact of evolocumab on changes in minimum FCT (interaction P = 0.04).

Conclusion: The ability of evolocumab to more effectively promote plaque stabilization, compared with statin monotherapy, appears more pronounced in patients with higher Lp(a) levels, suggesting that Lp(a) may help identify those who benefit most from intensive lipid-lowering therapy.

Registration: ClinicalTrials.gov: NCT03570697.

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