Low-Dose Combined Therapy with Fluvastatin and Cholestyramine in Hyperlipidemic Patients

doi:10.1059/0003-4819-120-7-199404010-00002

Low-Dose Combined Therapy with Fluvastatin and Cholestyramine in Hyperlipidemic Patients

From the Center for Cholesterol Research, University of Cincinnati Medical Center, Cincinnati, Ohio; University of New Mexico Hospital, Albuquerque, New Mexico; Heart Inc., The Hospital of the Good Samaritan, Los Angeles, California; Hennepin County Medical Center, Minneapolis, Minnesota; Oklahoma Cardiovascular and Hypertension Center and the University of Oklahoma, Oklahoma City, Oklahoma; Columbia University College of Physicians and Surgeons, New York, New York; Diabetes and Glandular Disease Research Center, San Antonio, Texas; University of Massachusetts Medical School, Worcester, Massachusetts; Institut de Cardiologie de Montreal, Montreal, Quebec; Sandoz Research Institute, East Hanover, New Jersey. Requests for Reprints: Dennis L. Sprecher, MD, Center for Cholesterol Research, University of Cincinnati Medical Center, University Hospital, 231 Bethesda Avenue, Mail Location 540, Cincinnati, OH 45267. Acknowledgments: The authors thank Joan Heggland, RN, for data collection, Rachel Neuwirth for analysis, and Martha Hoffmann for manuscript preparation. Grant Support: By Sandoz Pharmaceuticals Corporation, and Sandoz Canada, Inc.

Abstract

Objective: To compare the low-density lipoprotein (LDL) cholesterol-lowering efficacy of low-dose combinations of cholestyramine and fluvastatin.

Design: Randomized, double-blind, parallel group, placebo-controlled trial with a 24-week double-blind treatment period divided into three phases.

Setting: Office-based clinics.

Patients: Hypercholesterolemic, with LDL cholesterol of 4.14 mmol/L or greater (≥ 160 mg/dL) and plasma triglycerides of 3.39 mmol/L or less (≤ 300 mg/dL). Four hundred sixty patients were screened; 224 patients were randomized into a double-blind treatment period; 203 completed the study; 6 dropped out because of adverse events.

Intervention: Patients were treated with 10 mg or 20 mg of fluvastatin alone, 8 g or 16 g of cholestyramine alone, or combinations of these fluvastatin and cholestyramine dosages (six treatment groups).

Measurements: Changes in lipid variables, particularly LDL cholesterol.

Results: The 10-mg and 20-mg fluvastatin monotherapy groups showed considerable reductions in LDL cholesterol initially (−20.1% [SD, 8.8%] and −20.2% [SD, 10.1%], respectively); these reductions were maintained. Reductions in LDL cholesterol that resulted from the addition of cholestyramine, 8 g/d, to 10 mg of fluvastatin and 20 mg of fluvastatin were greater than those observed with monotherapy (10-mg fluvastatin − [10-mg fluvastatin plus cholestyramine], 9.1%; 95% CI, 3.8% to 14.4%) and 20-mg fluvastatin − [20-mg fluvastatin plus cholestyramine], 11.6%; CI, 6.5% to 16.8%). The increase in cholestyramine dose to 16 g/d in the three combination groups provided only a modest additional response.

Conclusions: Low-density lipoprotein cholesterol reductions of about 25% to 30% can be achieved with low-dose combination therapy with fluvastatin and cholestyramine. The addition of low-dose resin appears to produce greater overall cholesterol reduction than does a simple doubling of the fluvastatin dosage. The low-dose combination treatment was highly successful in achieving the goals of the National Cholesterol Education Program guidelines.