First Choice Lipid-Lowering Treatment of Hypercholesterolemias

Abstract

Several recent studies with lipid-lowering substances have shown a significant reduction in complications of this disease with drastic reduction of LDL-cholesterol levels. However, a huge proportion of patients in secondary prevention remain with inefficient treatment. Vastatins, also called statins, are considered worldwide as the first-line pharmacotherapy for the treatment of hypercholesterolemia, being the most efficient drugs to lower LDL-cholesterol, still presenting excellent tolerability. The main mechanism of action of vastatins is inhibition of the enzyme hydroxymethylglutaril-coenzyme A (HMG-CoA) reductase. Currently, the therapeutic arsenal for cases of family hypercholesterolemia and statin intolerance incorporated PCSK9 inhibitors (proprotein convertase subtilisin/kexin type 9) which is an enzyme that is involved in the degradation of the LDL- cholesterol receptor in the lysosome, preventing its recycling to the cell surface, thus reducing the amount of LDL- cholesterol receptors available, with consequent elevation of this lipid. Mutations with gain of function that lead to an increase in the expression of this enzyme cause, therefore, an increase in LDL- cholesterol, while mutations that lead to a decrease in its expression decrease LDL-cholesterol.