Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia.

OBJECTIVE To assess the lipid-lowering effect of atorvastatin (a new 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitor) on levels of serum triglycerides and other lipoprotein fractions in patients with primary hypertriglyceridemia, determine if atorvastatin causes a redistribution of triglycerides in various lipoprotein fractions, and assess its safety by reporting adverse events and clinical laboratory measurements. DESIGN Randomized double-blind, placebo-controlled, parallel-group, multicenter trial. SETTING Community- and university-based research centers. PATIENTS A total of 56 patients (aged 26 to 74 years) with a mean baseline triglyceride level of 6.80 mmol/L (603.3 mg/dL) and a mean baseline low-density lipoprotein cholesterol (LDL-C) level of 3.07 mmol/L (118.7 mg/dL). INTERVENTIONS Cholesterol-lowering diet (National Institutes of Health National Cholesterol Education Program Step I Diet) and either 5 mg, 20 mg, or 80 mg of atorvastatin, or placebo. MAIN OUTCOME MEASURES Percent change from baseline in total triglycerides for three dose levels of atorvastatin compared with placebo. RESULTS Mean reductions in total triglycerides between 5 mg, 20 mg, and 80 mg of atorvastatin and placebo after 4 weeks of treatment were -26.5%, -32.4%, -45.8%, and -8.9%, respectively. Mean reductions in LDL-C were -16.7%, -33.2%, -41.4%, and -1.4%, respectively, and very low-density lipoprotein cholesterol (VLDL-C) were -34.3%, -45.9%, -57.7%, and -5.5%, respectively. Similar mean changes in total apolipoprotein B (apo B) (-16.9%, -32.8%, -41.7%, and +1.0%), apo B in LDL (-14.8%, -29.8%, -42.0%, and -3.1%), and apo B in VLDL (-23.8%, -35.8%, -34.4%, and +11.7%) were observed. In addition, comparable mean changes in LDL triglycerides (-22.5%, -30.7%, -39.9%, and +3.9%) and VLDL triglycerides (-28.1%, -34.0%, -47.3%, and -10.8%) were seen. CONCLUSIONS In atorvastatin treatment groups, total serum triglyceride levels decreased in a dose-dependent manner, reductions in the 20-mg and 80-mg groups were statistically significant (P < .05) compared with placebo. Atorvastatin did not cause a redistribution of triglycerides but consistently lowered triglycerides in all lipoprotein fractions. Atorvastatin was well tolerated.

[1]  S. Grundy,et al.  Combination drug therapy for familial combined hyperlipidemia. , 1988, Annals of internal medicine.

[2]  M. Heimberg,et al.  Effects of free fatty acids on activity of hepatic microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase and on secretion of triglyceride and cholesterol by liver. , 1977, The Journal of biological chemistry.

[3]  S. Grundy,et al.  Two different views of the relationship of hypertriglyceridemia to coronary heart disease. Implications for treatment. , 1992, Archives of internal medicine.

[4]  Y. Hall,et al.  Assessing dietary adherence in the Multiple Risk Factor Intervention Trial (MRFIT). I. Use of a dietary monitoring tool. , 1980, Journal of the American Dietetic Association.

[5]  J. Fruchart,et al.  Differential electroimmunoassay of human LpA-I lipoprotein particles on ready-to-use plates. , 1990, Clinical chemistry.

[6]  J. Mckenney,et al.  Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II) , 1993, JAMA.

[7]  D. Sprecher,et al.  Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[8]  J. Albers,et al.  Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. , 1982, Clinical chemistry.

[9]  D R Jacobs,et al.  Retest reliability of plasma cholesterol and triglyceride. The Lipid Research Clinics Prevalence Study. , 1982, American journal of epidemiology.

[10]  G. Schonfeld,et al.  Apolipoprotein A-II content of human plasma high density lipoproteins measured by radioimmunoassay. , 1977, Journal of lipid research.

[11]  Richard H. Myers,et al.  Familial Lipoprotein Disorders in Patients With Premature Coronary Artery Disease , 1992, Circulation.

[12]  T. Südhof,et al.  Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D Feskanich,et al.  Comparison of a computerized and a manual method of food coding for nutrient intake studies. , 1988, Journal of the American Dietetic Association.

[14]  J. D. Proctor,et al.  A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients. , 1994, JAMA.

[15]  Plasma triglyceride and coronary heart disease. , 1991 .

[16]  R. Leboeuf,et al.  Mechanisms of triglyceride-lowering effect of an HMG-CoA reductase inhibitor in a hypertriglyceridemic animal model, the Zucker obese rat. , 1992, Journal of lipid research.

[17]  R. Bawol,et al.  Epidemiology as a guide to clinical decisions. The association between triglyceride and coronary heart disease. , 1980, The New England journal of medicine.