Fluvastatin and tissue factor pathway inhibitor in type IIA and IIB hyperlipidemia and in acute myocardial infarction

Abstract

Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor that regulates tissue factor-induced blood coagulation. In an open-label 8-week study, 20 hypercholesterolemic patients (10 type IIa and 10 type IIb) were enrolled and given fluvastatin 40 mg once daily at bedtime. At baseline (after a 4-week controlled diet) and at week 8, total cholesterol, total triglycerides and lipoprotein subfractions were assessed. TFPI antigen levels were measured at the same time by ELISA. We also measured TFPI concentrations in 10 control subjects and in 10 patients at the time of and ten days after acute myocardial infarction. In type IIa patients fluvastatin reduced total cholesterol levels by 26% and LDL-cholesterol by 30% (P < 0.001); in type IIb, fluvastatin significantly reduced total cholesterol levels by 24% (P < 0.001). In both dyslipidemic groups the baseline total TFPI levels were significantly higher than in the control group (P < 0.002). The therapeutic lipid-lowering effect was paralleled by a significantly reduction of total TFPI antigen concentrations from 132 +/- 23 to 71 +/- 37 ng/mL (P < 0.001) in type IIa and from 120 +/- 30 to 91 +/- 29 ng/mL (P < 0.05) in type IIb patients; in control subjects total TFPI levels were 81 +/- 22 ng/mL; however the lipoprotein-bound TFPI antigen subfractions did not differ significantly in the treated and control groups. In patients with recent myocardial infarction there was a significant reduction from day 0 to day 10 in total 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 treatment could be a sign of normalization of an up-regulated clotting system rather than an unfavourable reduction of a natural anticoagulant.