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  • Title: Plasma lipoprotein changes after treatment with pravastatin and gemfibrozil in patients with familial hypercholesterolemia.
    Author: Franceschini G, Sirtori M, Vaccarino V, Gianfranceschi G, Chiesa G, Sirtori CR.
    Journal: J Lab Clin Med; 1989 Sep; 114(3):250-9. PubMed ID: 2504855.
    Abstract:
    The ability of pravastatin, a new hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to lower plasma lipid levels and modify lipoprotein patterns was compared with that of gemfibrozil in 18 patients with familial hypercholesterolemia who participated in a 16-week, double-blind, parallel trial. Pravastatin proved better than gemfibrozil in lowering total and low-density lipoprotein (LDL) cholesterolemia: -23.6% and -28.2% versus -18.1% and -21.4%, respectively. A significant positive correlation was found between the starting level of serum cholesterol (both total and LDL) and the gemfibrozil-induced reduction (r = 0.72 and 0.69), whereas the hypocholesterolemic effect of pravastatin was apparently independent from pretreatment levels (r = 0.32 and 0.10). Apolipoprotein B concentrations were lowered by 25.4% (pravastatin) and 22.0% (gemfibrozil). Pravastatin and gemfibrozil reduced triglyceride levels by 13.9% and 49.4%, respectively. Both drugs increased the level of high density lipoprotein (HDL) cholesterol, but this change was significant only with gemfibrozil (p less than 0.05). The HDL subfraction structure and distribution were not modified by pravastatin treatment. Gemfibrozil, in contrast, increased HDL3 cholesterol level by 9% because of an enrichment of HDL3 particles in both free cholesterol and cholesteryl esters and lowered the flotation rate of HDL3 (p less than 0.05). LDL particles became smaller after gemfibrozil treatment (diameter: 25.4 +/- 0.3 nm vs 26.1 +/- 0.4 nm, p less than 0.01) and were not modified by pravastatin. This comparison shows a more pronounced efficacy of the HMG CoA reductase inhibitor on total and LDL cholesterol levels, also indicating that pravastatin acts by a single major mechanism, reducing the number of circulating LDL particles. Gemfibrozil may exert additional activities, possibly consequent to the stimulation of very low density lipoprotein catabolism.
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