LOW-DOSE COMBINED THERAPY WITH FLUVASTATIN AND CHOLESTYRAMINE IN HYPERLIPIDEMIC PATIENTS

Objective: To compare the low-density lipoprotein (LDL) cholesterol-lo wering efficacy of low-dose combinations of cholestyramine and fluvast atin. Design: Randomized, double-blind, parallel group, placebo-contro lled trial with a 24-week double-blind treatment period divided into t hree phases. Setting: Office-based clinics. Patients: Hypercholesterol emic, with LDL cholesterol of 4.14 mmol/L or greater (greater than or equal to 160 mg/dL) and plasma triglycerides of 3.39 mmol/L or less (l ess than or equal to 300 mg/dL). Four hundred sixty patients were scre ened; 224 patients were randomized into a double-blind treatment perio d; 203 completed the study; 6 dropped out because of adverse events. I ntervention: Patients were treated with 10 mg or 20 mg of fluvastatin alone, 8 g or 16 g of cholestyramine alone, or combinations of these f luvastatin and cholestyramine dosages (six treatment groups). Measurem ents: Changes in lipid variables, particularly LDL cholesterol. Result s: The 10-mg and 20-mg fluvastatin monotherapy groups showed considera ble reductions in LDL cholesterol initially (- 20.1% [SD, 8.8%] and - 20.2% [SD, 10.1%], respectively); these reductions were maintained. Re ductions in LDL cholesterol that resulted from the addition of cholest yramine, 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% Cl, 3.8% to 14.4%) and 20 -mg fluvastatin - [20-mg fluvastatin plus cholestyramine], 11.6%; Cl, 6.5% to 16.8%). The increase in cholestyramine dose to 16 g/d in the t hree combination groups provided only a modest additional response. Co nclusions: Low-density lipoprotein cholesterol reductions of about 25% to 30% can be achieved with low-dose combination therapy with fluvast atin and cholestyramine. The addition of low-dose resin appears to pro duce greater overall cholesterol reduction than does a simple doubling of the fluvastatin dosage. The low-dose combination treatment was hig hly successful in achieving the goals of the National Cholesterol Educ ation Program guidelines.