LDL-C Target Attainment and Treatment Gaps Six Months After Acute Coronary Syndrome: insights from the CALLINICUS-Hellas registry

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) reduction is the cornerstone of secondary prevention after acute coronary syndrome (ACS). Despite potent lipid-lowering therapies (LLTs), a therapeutic gap persists. We aimed to evaluate LDL-C target attainment according to the 2019 ESC/EAS guidelines, identify predictors of treatment failure, and simulate the impact of treatment intensification. METHODS: The CALLINICUS-Hellas registry is a prospective, multicenter study of patients with ACS. LDL-C target attainment at 6 months, defined as LDL-C reduction ≥50% from baseline and an LDL-C <55 mg/dL, was assessed. Simulation modeling explored four guideline-recommended LLT intensification scenarios. Hierarchical cluster analysis aimed to identify patient phenotypes associated with goal attainment. RESULTS: Among 1,947 patients, 37.9% achieved LDL-C target at 6 months. The main driver of treatment failure was clinical inertia, with <1% of patients receiving PCSK9 inhibitors at follow-up. Persistent smoking at 6 months, lipoprotein(a) >70 mg/dL, higher untreated LDL-C levels and heterozygous familial hypercholesterolemia were associated with treatment failure while high-intensity statin (HIS) ± ezetimibe (EZE) at discharge was the most prominent predictor of treatment attainment (all p-values <0.05). Cluster analysis confirmed that target attainment depended on discharge LLT intensity, not clinical phenotypes. Simulation analysis showed that universal HIS ± EZE at discharge could increase target attainment to 51%, whereas optimal triple LLT (HIS + EZE + PCSK9 inhibitors) could increase it to 97.7%. CONCLUSIONS: Despite progress, LDL-C target attainment after ACS remains suboptimal, largely due to clinical inertia and guideline-recommended LLT underuse. Early initiation of combination LLT after ACS could substantially improve target attainment.