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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1527-1531.)
© 1997 American Heart Association, Inc.

Articles

Atorvastatin: An Effective Lipid-Modifying Agent in Familial Hypercholesterolemia

A. David Marais; Jean C. Firth; Mary E. Bateman; Pam Byrnes; Candice Martens; ; Jean Mountney

From the Department of Medicine, University of Cape Town Medical School, Cape Town, and Parke-Davis Pharmaceuticals (C.M.), South Africa.

Correspondence to Dr A.D. Marais, Department of Internal Medicine, University of Cape Town Medical School, Observatory 7925, Cape Town, South Africa. E-mail dmarais{at}uctgsh1.uCT.ac.za

Abstract Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo 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 were 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 concentration decreased from 9.90±1.32 to 5.43 mmol/L (P<.001). HDL cholesterol 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 increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Ator- vastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH.

Key Words: atorvastatin • HMG-CoA reductase inhibitors • familial hypercholesterolemia

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