Impact of intensive lipid lowering therapy with evolocumab on plaque phenotype changes in acute coronary syndrome patients with elevated lp(a) levels: a huygens sub study.

Abstract

Aim: Despite increased use of PCSK9 inhibitors in intensive LDL-C lowering therapy, the impact on plaque phenotype changes in acute coronary syndrome (ACS) patients with different Lp(a) levels is unclear. Method(s): Serial optical coherence tomography imaging was performed to evaluate changes in plaque composition in response to treatment with evolocumab 420 mg or placebo for 52 weeks. The current analysis compared changes in those with baseline Lp(a) levels >=125 nmol/L (n=46) and <125 nmol/L (n=71). Result(s): Among those with high Lp(a) levels, evolocumab treatment produced lower levels of LDL-C (21.7+/-10.3 vs 94.5+/-22.9 mg/dL; p<0.0001) and Lp(a) (156.0 [136.0, 187.0] vs 204.0 [170.5, 290.5] nmol/L; p=0.007), compared to placebo. Changes in minimum fibrous cap thickness (FCT) (51.6+/-40.9mum vs 12.4+/-23.9mum; p=0.0004) and lipid arc (-60.9+/-56.5o vs -9.1+/-70.8o; p=0.008) were greater in the high Lp(a) group with evolocumab compared to 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<0.0001) and Lp(a) (11.5 [5.8, 23.8] vs 25.0 [13.5, 41.0] nmol/L; p=0.01) compared to placebo, but no differences were observed between groups in changes in minimum FCT (45.9+/-37.8mum vs 34.7+/-36.0mum; p=0.21) and lipid arc (-59.9+/-50.1o vs -44.5+/-46.1o; p=0.18). Baseline Lp(a) levels significantly interacted with the impact of evolocumab on changes in minimum FCT (P=0.04) and lipid arc (P=0.08). Conclusion(s): The ability of evolocumab to promote plaque stabilisation appears to be more prominent in patients with higher Lp(a) levels, potentially offering insight into the modifiability of atherosclerosis.Copyright © 2024