Background: Depending on individual differences in cholesterol homeostatis LDL-C reductions on monotherapy with statins, ezetimibe, PCSK9-mAbs and inclisiran demonstrate a high inter-individual variability. The impact of individual differences in cholesterol metabolism on inter-individual variability and effectiveness of LDL-C reductions on combined lipid-lowering therapy with atorvastatin 80 mg and ezetimibe 10 mg is so far unknown. 

Methods: In this prospective cohort study (Jena auf Ziel – “JaZ”) we evaluate in patients with ST-elevation myocardial infarctions (STEMI) the variability of LDL-C reductions on combined lipid-lowering therapy with atorvastatin 80mg/ezetimibe 10 mg in relation to individual differences in cholesterol metabolism.  Patients on lipid-lowering therapy on admission were excluded from the analysis, so that a total of n=39 patients were evaluated. On the day of admission total cholesterol, HDL, LDL and TGs were obtained using standard techniques. Moreover, gas chromatography-flame ionization analysis was performed for quantification of cholesterol and mass spectroscopy was performed for markers for endogenous cholesterol synthesis (e.g. lathosterol, lanosterol) and markers for cholesterol absorption (e.g. sitosterol, campesterol). After 6-8 weeks on combined lipid-lowering therapy differences in LDL-C reductions were assessed in relation to individual differences in cholesterol metabolism. 

Results: Combined lipid-lowering therapy with atorvastatin 80mg and ezetimibe 10 mg reduced LDL-C after 6-8 weeks effectively compared to baseline with low inter-individual variability. Individual LDL-C reductions attained with combined lipid-lowering therapy ranged between 47-87% (figure 1). Analyzing individual differences in cholesterol metabolism sitosterol/cholesterol (r=0.335; p<0.05) as a ratio indicative of high cholesterol absorption at baseline was positively associated to lower LDL-C reduction efficacy, whereas markers for cholesterol synthesis (e.g. lathosterol/cholesterol) showed a trend towards more effective LDL-C reductions (figure 2).

Conclusion: Combined lipid lowering therapy with atorvastatin 80 mg / ezetimbe 10 mg is associated with effective LDL-C reductions and low inter-individual variability. These data further support the early initiation of a combined lipid lowering therapy with a high intensity statin (atorvastatin 80 mg) and a cholesterol absorption inhibitor (ezetimibe 10 mg) in patients with STEMI.