COMPARISON OF LIPID-LOWERING EFFECTS OF LOW-DOSE FLUVASTATIN AND CONVENTIONAL-DOSE GEMFIBROZIL IN PATIENTS WITH PRIMARY HYPERCHOLESTEROLEMIA

A total of 123 patients with primary hypercholesterolemia were randomi zed on a 2:1 ratio to receive either fluvastatin at 20 mg once daily a t night (n = 82) or gemfibrozil at 600 mg twice daily (n = 41) in a do uble-blind, double-dummy comparison of the effects on plasma lipid par ameters and tolerability over 8 weeks. All patients had either low-den sity Lipoprotein cholesterol (LDL-C) concentrations greater than or eq ual to 160 mg/dL (4.1 mmol/L) in association with definite coronary ar tery disease (CAD) or greater than or equal to 2 risk factors, or LDL- C greater than or equal to 190 mg/dL (4.9 mmol/L) with no CAD and < 2 risk factors. All had triglyceride (TG) levels less than or equal to 3 50 mg/dL (4.0 mmol/L). After 8 weeks of treatment, fluvastatin produce d significant reductions from baseline of 17.4% (p < 0.001) in LDL-C, 13.2% (p < 0.001) in total cholesterol (TC), 13.8% (p < 0.001) in very low-density lipoprotein cholesterol (VLDL-C), and 6.4% (NS) in TG. Hi gh-density Lipoprotein cholesterol (HDL-C) was increased by 5.6% (p < 0.001), and the ratio of LDL-C:HDL-C (Friedewald) was decreased by 21. 2% (p < 0.001). Gemfibrozil reduced LDL-C by 15.8%, TC by 13.4%, VLDL- C by 32.2%, LDL-C:HDL-C by 24.8%, and TG by 34.2%, and increased HDL-C by 13.9% (all changes were statistically significant, p < 0.001) comp ared with baseline. Gemfibrozil produced significantly greater changes in VLDL-C (p < 0.01), HDL-C (p < 0.001), and TG (p < 0.001), but not in LDL-C: HDL-C, compared with fluvastatin. Both drugs significantly r educed apolipoprotein (ape) B and lipoparticles (Lp) E:B, and increase d ape A-I but had divergent effects on LpA-I (increased with fluvastat in and reduced with gemfibrozil; p < 0.05). At the end of the study, 4 3.8% of fluvastatin patients and 45% of gemfibrozil patients achieved a reduction of > 20% in LDL-C levels. Normalization of LDL-C levels wa s achieved (according to European Atherosclerosis Society guidelines) by 13.4% of fluvastatin- and 14.6% of gemfibrozil-treated patients. Bo th drugs were well tolerated; adverse events occurred in 36.6% of fluv astatin recipients compared with 58.5% of patients taking gemfibrozil. No clinically notable elevations of aspartate or alanine aminotransfe rases, alkaline phosphatase, or creatine phosphokinase occurred. No pa tient developed new or worsening lens opacities associated with a redu ction in optically corrected visual acuity. The most commonly reported adverse events were headache and gastrointestinal upset. There were n o serious drug-related adverse events.