ATORVASTATIN - AN EFFECTIVE LIPID-MODIFYING AGENT IN FAMILIAL HYPERCHOLESTEROLEMIA

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are th e drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study w as conducted to test the efficacy and safety of atorvastatin, a new sy nthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week place bo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n=11) or 40 mg twice a day for 6 weeks. The two dosage groups w ere well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8 .16+/-1.15 to 3.53+/-0.99 mmol/L (P<.001). The total cholesterol conce ntration decreased from 9.90+/-1.32 to 5.43 mmol/L (P<.001). HDL chole sterol concentration increased from 1.19+/-0.31 to 1.49+/-0.43 mmol/L (P<.001). Triglyceride concentrations decreased from 1.34+/-0.66 to 0. 88+/-0.36 mmol/L (P<.01). Three subjects had single, transient increas es of serum transaminase of up to twice the upper limit of normal. Apo lipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nonden aturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentrati on increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modif ying agent for LDL cholesterol; it also modifies HDL cholesterol and t riglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH.