Kombinace statinů s inhibitorem absorpce cholesterolu: strategie pro dosažení cílových hodnot lipidů

Cor Vasa 2004, 45(2):80-83

Combinations of statins with a cholesterol absorption inhibitor: a strategy for reaching goal lipid levels

Helena Vaverková: III. interní klinika, Fakultní nemocnice a Lékařská fakulta Univerzity Palackého, Olomouc, Česká republika

Large intervention lipid-lowering trials have demonstrated a decrease in LDL-cholesterol (LDL-C) levels results in a reduction in the risk for cardiovascular morbidity and overall mortality both in primary and secondary prevention. Despite this major development, only about one in three patients receiving secondary prevention in the Czech Republic will attain goal lipid levels (as defined by current guidelines); this is consistent with data reported from industrialized Western nations. While maximum doses of highly effective statins (atorvastin, simvastatin) will produce goal levels of total cholesterol and LDL-C in most individuals-even in secondary prevention-they are associated with a manifold increase in the incidence of side effects, and an increase in liver enzymes in particular. Moreover, a doubling of statin dose will only result in an additional 6% reduction in LDL-C (rule 6). Hence, a suitable strategy could be combination therapy using basic doses of a statin plus another lipid-lowering drug with a complementary mode of action, not increasing toxicity and well tolerated (an alternative to combination therapy in hypertension, currently the preferred option). A novel drug suitable for combination therapy is the lipid-lowering agent ezetimibe (Ezetrol®), the first drug of a new class of dietary and biliary cholesterol intestinal absorption inhibitors. At a daily dose of 10 mg, ezetimibe reduces LDL-C levels by 18% both in monotherapy and when combined with statins. When co-administered with the lowest dose of a statin, ezetimibe will produce the same reduction in LDL-C as the highest dose of the same statin in monotherapy. In terms of tolerability, ezetimibe has a profile similar to that of placebo; its co-administration with a statin will not increase the incidence of side effects compared with monotherapy using the statin at the above dose. This combination therapy using the principle of dual inhibition (statin-based cholesterol synthesis inhibition and ezetimibe-based intestinal cholesterol absorption inhibition) could thus possibly improve patient compliance helping them attain goal cholesterol levels required for cardiovascular event prevention.