Efficacy of a combination of cholesterol absorption and synthesis inhibitors in the correction of hyperlipidemia and dietary fat intolerance in patients with coronary heart disease (ESTHETICS trial)

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Abstract

Objective: to study the lipid-modifying effects of the selective intestinal cholesterol absorption inhibitor ezetimibe as monotherapy and in combination with simvastatin, an inhibitor of hydroxy methyl glutaryl coenzyme A (HMG-CoA) reductase, a key enzyme in cholesterol synthesis, which is given on an empty stomach and after single dietary fat intake (FI) that modulates postprandial hyperlipidemia (HL) in coronary heart disease (CHD) patients with baseline HL. Subjects and method. The trial covered 30 patients aged 43–75 years with CHD and baseline HL of Types IIa and IIb (Fredrickson classification) who were, after 4-week therapy, randomized to 2 groups: 1) 15 patients took ezetimibe 10 mg/day and 2) 15 received simvastatin 20 mg/day (the total duration of monotherapy was 12 weeks), then its half dose (from 20 to 10 mg/day) added by ezetimibe 10 mg/day (the duration of the combination therapy was 12 weeks). All the patients underwent standard FI test before and after a 12-week monotherapy period and 24 weeks (i.e. after 12-weel combination therapy). A standard FI test was carried out by the modified procedure described by J. Patsch (1983); the cutoffs for blood sampling for analysis were on an empty stomach (before FI) and 3 and 6 hours after FI. Results. The patients with CHD treated with ezetimibe 10 mg showed a significant reduction in the fasting levels of total cholesterol (TC) by 20% (p<0,001), low-density lipoprotein cholesterol (LDL-C) by 25% (p<0,001), triglycerides (TG) by 25% (p<0,01), and apolipoprotein B by 20% (p<0,001). Ezetimibe monotherapy resulted in a significant decrease in the postprandial concentrations of TC and non-high-density lipoprotein cholesterol (non-HDL-C). A combination of hypolipidemic drugs (ezetimibe 10 mg + simvastatin 10 mg) provides an additional positive effect in lowering the postprandial (at 6 hours of FI) concentrations of TC by 9,1% (p<0,001) and non-HDL-C by 10,9% (p<0,001). The time course of changes in the levels of TG was significantly unchanged in response to FI while its mean postprandial levels were lower than those before treatment. The atherogenic TC/HDH-C ratio was reduced: its value decreased after FI by 40,3% (p<0,001) at 6 hours relative to the baseline values. Conclusion. Monotherapy with ezetimibe and simvastatin and, to a greater extent, their combination alleviate postprandial HL that is of greater importance in atherogenesis than the isolated increase in serum LDL-C. This noticeably enhances lipid-transporting system resistance to the atherogenic effect of dietary fats in patients with CHD.

About the authors

M. G Bubnova

State Research Center for Preventive Medicine, Ministry of Health of the Russian Federation

Email: mbubnova@gnicpm.ru
д-р мед. наук, проф., рук. отд. реабилитации и вторичной профилактики сочетанной патологии с лабораторией профилактики атеросклероза и тромбоза ФГБУ ГНИЦ ПМ Минздрава РФ

N. V Perova

State Research Center for Preventive Medicine, Ministry of Health of the Russian Federation

д-р мед. наук, проф., вед. науч. сотр. отд. изучения биохимических маркеров хронических неинфекционных заболеваний ФГБУ ГНИЦ ПМ Минздрава РФ

D. M Aronov

State Research Center for Preventive Medicine, Ministry of Health of the Russian Federation

д-р мед. наук, проф., засл. деят. науки РФ, рук. лаб. кардиологической реабилитации ФГБУ ГНИЦ ПМ Минздрава РФ

A. A Zeinapur

State Research Center for Preventive Medicine, Ministry of Health of the Russian Federation

канд. мед. наук, зав. приемным отд-нием ФГБУ ГНИЦ ПМ Минздрава РФ

I. N Ozerova

State Research Center for Preventive Medicine, Ministry of Health of the Russian Federation

канд. биол. наук, вед. науч. сотр. отд. изучения биохимических маркеров хронических неинфекционных заболеваний ФГБУ ГНИЦ ПМ Минздрава РФ

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