January 10, 1996

Efficacy and Safety of a New HMG-CoA Reductase Inhibitor, Atorvastatin, in Patients With Hypertriglyceridemia

Author Affiliations

From Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co, Ann Arbor, Mich (Mss Bakker-Arkema and Shurzinske and Dr Black); Chicago (Ill) Center for Clinical Research (Dr Davidson); Clinical Research Institute, Montreal, Quebec (Dr Davignon); Christ Hospital Cardiovascular Research Center, Cincinnati, Ohio (Dr Isaacsohn); San Diego (Calif) Endocrine and Medical Clinic Inc (Dr Weiss); Clinical Research Management, Center for Lipids, Portland, Me (Dr Keilson); Division of Arteriosclerosis and Lipid Metabolism, Emory University School of Medicine, Atlanta, Ga (Dr Brown); and Lipid Research Clinic, George Washington University Medical Center, Washington, DC (Dr Miller). Dr Goldstein is in private practice in Tampa, Fla.

JAMA. 1996;275(2):128-133. doi:10.1001/jama.1996.03530260042029

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.(JAMA. 1996;275:128-133)