Predicting LDL-cholesterol reduction variability on statin–ezetimibe therapy: insights from “Jena auf Ziel”

Background and aims Low-density lipoprotein cholesterol (LDL-C) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). ESC/EAS guidelines recommend reducing LDL-C < 1.4 mmol/L and > 50% from baseline in patients with myocardial infarction. “Jena auf Ziel” (JaZ) is a prospective cohort study in which early combination therapy with atorvastatin 80 mg and ezetimibe 10 mg was initiated on admission in patients with ST-elevation myocardial infarction (STEMI) to reduce LDL‑C levels early and effectively. Methods In this secondary analysis, we included 42 patients who were naïve to lipid-lowering therapy (LLT) on admission. Aim of the current analysis was to assess individual variations in LDL‑C response and to investigate the associations between plasma surrogate markers of cholesterol metabolism at baseline and LDL‑C reductions after 4–6 weeks on combined LLT. Results Combined LLT with atorvastatin 80 mg and ezetimibe 10 mg reduced LDL‑C after 6 weeks in all patients very effectively (47.7–92.5%) across all quartiles of cholesterol absorption and synthesis markers. No statistically significant differences in LDL‑C reduction were observed across quartiles of cholesterol metabolism markers, although Pearson correlation analysis indicated a modest association between sitosterol:cholesterol and LDL‑C response. The median LDL‑C reduction was > 60% in all quartiles of cholesterol absorption (sitosterol:cholesterol, campesterol:cholesterol, cholestanol:cholesterol) and synthesis markers (lathosterol:cholesterol). We found no statistically significant differences regarding the LDL‑C change from baseline (%) in quartiles of sitosterol:cholesterol, campesterol:cholesterol, cholestanol:cholesterol (markers of cholesterol absorption), and lathosterol:cholesterol (marker of cholesterol synthesis). However, Pearson correlation values indicated a correlation between sitosterol:cholesterol and LDL‑C reduction with higher ratios being associated with less pronounced LDL‑C reduction. Conclusion Upfront dual therapy with atorvastatin (80 mg) and ezetimibe (10 mg) achieved robust LDL‑C reduction with low interindividual variability in treatment-naive individuals. We found no significant association between baseline cholesterol metabolism markers and treatment response. This supports current guideline recommendations for immediate combination therapy in very high-risk patients, irrespective of their baseline metabolic phenotype.