EFFECTS OF FLUVASTATIN AND PRAVASTATIN ON LIPID PROFILES AND THROMBOXANE PRODUCTION TYPE IIA HYPERCHOLESTEROLEMIA

The aim of this study was to assess the effects of fluvastatin and pra vastatin on lipid profiles and urinary thromboxane (TX) A(2) metabolit es (11-dehydro TXB(2) and 2,3-dinor TXB(2)) in patients with type Ila hypercholesterolemia. A total of 20 patients (13 men, 7 women; mean ag e 53 +/- 9 years) with primary type Ila hypercholesterolemia (Fredrick son's classification) in a 4-week, double-blind, parallel-group study were randomized to fluvastatin or pravastatin, both at 40 mg once dail y (at bedtime), after a single-blind, 4-week, placebo run-in period. T otal cholesterol, low density lipoprotein cholesterol (LDL-C), high de nsity lipoprotein cholesterol (HDLC), 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 a n enzyme immunoassay kit, in 12 hr urine samples. At baseline, the mea n +/- SD levels of total cholesterol, LDL-C, triglycerides, and HDL-C were: 292 +/- 23, 213 +/- 47, 186 +/- 119 and 41 +/- 17 mg/dL with flu vastatin; 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 chole sterol 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, an d from 43 +/- 10 to 46 +/- 12 mg/dl with pravastatin. Triglycerides we re decreased with fluvastatin (from 186 +/- 119 to 125 +/- 54 mg/dL), although not significantly. The ratio of total cholesterol : HDL-C dec reased from 7.1 to 3.6 with fluvastatin, and from 7.0 to 5.04 with pra vastatin. No significant changes in thromboxane-metabolite excretion w ere observed with either treatment in comparison to baseline values. C orrelations between total cholesterol and thromboxane metabolites pres ent 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-te rm studies are needed to investigate, in addition to cholesterol-lower ing actions, the possible effects of various 3-hydroxy-3-methylglutary l-coenzyme A reductase inhibitors on the mechanism(s) associated with enhanced atherothrombotic risk, such as increased thromboxane-metaboli te production, in hypercholesterolemic patients.