Causes Underlying the Reduced Response to Simvastatin Treatment in Hypercholesterolemic Patients
Simvastatin, a competitive inhibitor of HMG-CoA reductase, effectively reduces elevated plasma cholesterol levels by up regulating the LDL receptor expression. Therefore in patients whose hypercholesterolemia (HC) is due to a defective LDL-receptor interaction vastatins may not be as effective as expected. To verify this hypothesis we studied the possible causes for the poor response (<15% decrease of LDL cholesterol) to simvastatin (40 mg/die) in 11 HC patients. Biochemical defects were identified in 5 patients. Three patients presented with binding-defective LDL, without the 3500 mutation, and the remaining two had normal LDL but their serum contained factors interfering with the LDL-receptor interaction. From these results we conclude that distinct biochemical defects might contribute to the poor response to simvastatin in hypercholesterolemic patients.
Key wordsLDL receptor binding defective LDL hypolipidaemic drugs apolipoprotein B probucol
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