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

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.