ESCADRA: a randomised study. Part I: lipid-lowering effectiveness, safety and tolerability of ezetimibe, initial doses of original statins, and the combination of ezetimibe with initial doses of statins in patients with coronary heart disease and hyperlipidemia

Aim. To study the lipid-lowering effectiveness, as well as the effects on inflammatory markers and vascular wall function, of ezetimibe as monotherapy and in combination with initial doses of original statins (simvastatin, atorvastatin, and rosuvastatin). Material and methods. The study included 60 male and female patients with coronary heart disease and hyperlipidemia. Mean age of the participants was 61,4 years; mean baseline level of low-density lipoprotein cholesterol (LDL-CH) was 4,1 mmol/l. The participants were randomised into four groups: ezetimibe monotherapy (10 mg/d) for 24 weeks, or statin monotherapy (simvastatin, atorvastatin, or rosuvastatin; 10 mg/d) for 12 weeks with following assessment of LDL-CH levels. If target levels were not achieved on statin monotherapy, a combination of ezetimibe and statins was administered for the next 12 weeks. The effects of monotherapy and combined therapy on lipid profile, C-reactive protein, pro-inflammatory cytokines, vascular elasticity and stiffness, as well as treatment tolerability, were assessed. Results. After 3 months of the treatment, LDL-CH levels in statin monotherapy groups decreased to 2,66-2,98 mmol/l. The decrease in LDL-CH concentration in ezetimibe group (-16,4 %) was significant. After 3 months, the percentage of the patients with achieved target LDL-CH levels was 17 % for ezetimibe, 42 % for simvastatin, 31 % for atorvastatin, and 58 % for rosuvastatin. After 6 months, the patients receiving combined therapy demonstrated LDL-CH reduction by 39,5-50,6 %. From Month 3 to Month 6, the additional lipid-lowering effect of ezetimibe, as a part of combined therapy, varied from 13 % to 25,9 %. Conclusion: Adding ezetimibe (10 mg/d) to any statins reduces LDL-CH levels by extra 20-30 %. Combined therapy was required in over 50 % of the patients. Therefore, the response to statin monotherapy is not universal and in one-third of the patients could be regarded as poor. In these individuals, the “double inhibition” approach (combining statins with ezetimibe 10 mg/d) could control LDL-CH levels more effectively.