FLUVASTATIN AND TISSUE FACTOR PATHWAY INHIBITOR IN TYPE IIA AND IIB HYPERLIPIDEMIA AND IN ACUTE MYOCARDIAL-INFARCTION

Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor that regulates tissue factor-induced blood coagulation. In an open-lab el 8-week study, 20 hypercholesterolemic patients (10 type IIa and 10 type IIb) were enrolled and given fluvastatin 40 mg once daily at bedt ime. At baseline (after a 4-week controlled diet) and at week 8, total cholesterol, total triglycerides and lipoprotein subfractions were as sessed. TFPI antigen levels were measured at the same time by ELISA. W e also measured Tf;PI concentrations in 10 control subjects and in 10 patients at the time of and ten days after acute myocardial infarction . type IIa patients fluvastatin reduced total cholesterol levels by 26 % and LDL-cholesterol 30% (P<0.001); in type IIb, fluvastatin signific antly reduced total cholesterol levels by 24% (P<0.001). In both dysli pidemic groups the baseline total TFPI levels were significantly highe r than in the control group (P<0.002). The therapeutic lipid-lowering effect was paralleled by a significantly reduction of total TFPI antig en concentrations: from 132 +/- 23 to 71 +/- 37 ng/mL (P<0.001) in typ e IIa and from 120 +/- 30 to 91 +/- 29 ng/mL (P<0.05) type IIb patient s; in control subjects total TFPI levels were 81 +/- 22 ng/mL; however lipoprotein-bound TFPI antigen subfractions did not differ significan tly in the treated control groups. In patients with recent myocardial infarction there was a significant reduction from day 0 to day 10 in t otal TFPI antigen levels, from 120 +/- 48 ng/mL to 80 16 ng/mL (P<0.05 ). The reported reduction of TFPI antigen levels after fluvastatin tre atment could be a sign of normalization of an up-regulated clotting sy stem rather than unfavourable reduction of a natural anticoagulant. (C ) 1997 Elsevier Science Ltd.