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

1 April 1994 | Volume 120 Issue 7 | Pages 537-543

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.

Author and Article Information

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.