Atorvastatin: An Effective Lipid-Modifying Agent in Familial Hypercholesterolemia

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. Atorvastatin 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.

Effects on Serum Uric Acid by Difference of the Renal Protective Effects with Atorvastatin and Rosuvastatin in Chronic Kidney Disease Patients

“…21) In addition, Marais et al administered ATV (80 mg/d) for 6 weeks to 22 patients with familial hypercholesterolemia, and reported that SUA levels decreased by approximately 10% from 4.87 to 4.36 mg/dL. 22) The SUA-lowering effect of ATV in these patients is the result of a dose that far exceeds the maximum daily dose of 20 mg allowed in Japan. In this study, we could demonstrate the SUA-lowering effect of ATV at the average dose of 8.8 mg/d, which is less than the dose reported previously.…”

Effect of Atorvastatin on High-Density Lipoprotein Apolipoprotein A-I Production and Clearance in the New Zealand White Rabbit

“…Several large clinical trials examining lipoprotein and apolipoprotein responses with atorvastatin have shown HDL cholesterol and apoA-I increases of 3% to 8% at lower doses of atorvastatin (10 to 20 mg), 3,7,8,13 whereas at higher doses (40 to 80 mg atorvastatin), levels of HDL cholesterol and apoA-I are generally either minimally elevated or not significantly different from placebo. 3,7,8,20 In general, the rise in apoA-I, the major protein component of HDL, tends to be smaller than that of HDL cholesterol. 7,8,13,20 For example, in comparative human trials of simvastatin and atorvastatin therapies, both the apoA-I and HDL cholesterol percentage increases tended to be lower with high-dose atorvastatin versus simvastatin regimens but were significantly lower only for the apoA-I response.…”

“…3,7,8,20 In general, the rise in apoA-I, the major protein component of HDL, tends to be smaller than that of HDL cholesterol. 7,8,13,20 For example, in comparative human trials of simvastatin and atorvastatin therapies, both the apoA-I and HDL cholesterol percentage increases tended to be lower with high-dose atorvastatin versus simvastatin regimens but were significantly lower only for the apoA-I response. 7,8 As observed in humans, in the rabbits in the present study, the apoA-I response to high-dose atorvastatin was more negative than the HDL cholesterol response 3 weeks after treatment (Ϫ4.2% change in HDL cholesterol and Ϫ19.4% change in apoA-I).…”

Microsomal Transfer Protein Inhibitors, New Approach for Treatment of Familial Hypercholesterolemia, Review of the Literature, Original Findings, and Clinical Significance

“…The drugs in use include pitavastatin, rosuvastatin, atorvastatin, simvastatin, fluvastatin, pravastatin, and lovastatin. There is considerable variation in the statin lowering response of LDL cholesterol (À25 to 60%) [45,46]. Genetic determinants of responsiveness to the statins cannot be excluded [47].…”