Effets of fluvastatin and pravastatin on lipid profiles and thromboxane production in type IIa hypercholesterolemia

Abstract

The aim of this study was to assess the effects offluvastatin and pravastatin on lipid profiles and urinary thromboxane (TX) A 2 metabolites (11-dehydro TXB 2 and 2,3-dinor TXB 2) in patients with type IIa hypercholesterolemia. A total of 20 patients (13 men, 7 women; mean age 53 ± 9 years) with primary type IIa hypercholesterolemia (Fredrickson's classification) in a 4-week, double-blind, parallel-group study were randomized to fluvastatin or pravastatin, both at 40 mg once daily (at bedtime), after a single-blind, 4-week, placebo run-in period. Total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides were measured after placebo (baseline) and after 4 weeks of double-blind treatment. Thromboxane metabolites were measured at the same time points, using an enzyme immunoassay kit, in 12 hr urine samples. At baseline, the mean ± SD levels of total cholesterol, LDL-C, triglycerides, and HDL-C were: 292 ± 23, 213 ± 47, 186 ± 119 and 41 ± 17 mg/dL with fluvastatin; and 301 ± 40, 212 ± 40, 150 ± 124 and 43 ± 10 mg/dL with pravastatin, respectively. Baseline thromboxane-metabolite levels were positively and significantly (p <0.04) correlated with levels of total cholesterol, but not LDL-C. Compared with baseline, total cholesterol and LDL-C were significantly (p <0.01) decreased by 27% and 30% with fluvastatin, and by 23% and 31 %with pravastatin, respectively. HDL-C increased from 41 ± 17 to 59 ± 25 mg /dL with fluvastatin, and from 43 ± 10 to 46 ± 12 mg/dL with pravastatin. Triglycerides were decreased with fluvastatin (from 186 ± 119 to 125 ± 54 mg/dL), although not significantly. The ratio of total cholesterol : HDL-C decreased from 7.1 to 3.6 with fluvastatin, and from 7.0 to 5.04 with pravastatin. No significant changes in thromboxane-metabolite excretion were observed with either treatment in comparison to baseline values. Correlations between total cholesterol and thromboxone metabolites present at baseline had disappeared after 4 weeks of treatment. Short-term treatment with fluvastatin and pravastatin, both at 40 mg once daily, resulted in similar reductions in total cholesterol and LDL-C. There was a trend in favor of fluvastatin in reducing triglycerides. Long-term studies are needed to investigate, in addition to cholesterol-lowering actions, the possible effects of various 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on the mechanism(s) associated with enhanced atherothrombotic risk, such as increased thromboxane-metabolite production, in hypercholesterolemic patients.