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  • Title: [Hypercholesterolemia: therapeutic approach].
    Author: Alessandri C, Peverini F.
    Journal: Clin Ter; 1991 Jun 30; 137(6):373-97. PubMed ID: 1832610.
    Abstract:
    Epidemiological observations, experimental and clinical researches have laid special stress on the importance of hypercholesterolemia in the natural development of the atherosclerotic disease and its cardiovascular complications. Primary and secondary trials have demonstrated the benefits of cholesterol-lowering therapy to modify the evolution of atherosclerotic disease. In particular, it was observed a significant reduction of incidence and mortality due to coronary heart disease, that is the most common complication of atherosclerosis. At the present time, we have a new class of cholesterol-lowering drugs which is able to inhibit the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, the enzyme limiting the endogenous pathway of cholesterol synthesis. The HMGCoA reductase inhibitors, according to the chemical structure, can be divided into two groups. The first includes inactive lactone prodrugs, as Lovastatin and Simvastatin, that are enzymatically hydrolyzed to the corresponding ring-opened active forms in the liver, where the HMGCoA reductase inhibitors must chiefly reduce cholesterol synthesis. To the other group belongs the Pravastatin, a drug that is administered in its active open hydroxyacid form. Several clinical studies seem to demonstrate a greater cholesterol-lowering effect of the active form of Simvastatin, probably because of its more affinity for the HMGCoA reductase enzyme. Up to now, no inhibitor of HMGCoA reductase has showed serious toxic effects in man. The remarkable therapeutic efficacy showed by Simvastatin to reduce the serum concentrations of total and LDL-cholesterol, associated with moderate side-effects, ascribes to this molecule an important role in the therapeutic approach of familial and polygenic hypercholesterolemia.
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