Treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors in hypercholesterolemia induces changes in the components of the extrinsic coagulation system.

The present study was performed to determine the influence of pharmaceutical intervention on parameters of blood coagulation and fibrinolysis in hypercholesterolemic patients. Eighteen otherwise-healthy individuals with heterozygous familial hypercholesterolemia were treated with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (simvastatin, 40 mg daily) for 12-14 weeks followed by additional treatment with omega-3 fatty acids (equivalent to 4 g eicosapentaenoic acid/docosahexaenoic acid daily) for 6 more weeks. With simvastatin treatment, the mean decreases in total cholesterol, low density lipoprotein (LDL) cholesterol, and apolipoprotein B (apo B) were 39%, 46%, and 36%, respectively. Only minor changes in high density lipoprotein (HDL) cholesterol and apo A-1 were recorded. omega-3 fatty acids had minor additional effects. The most prominent effects on the blood coagulation system were the changes in extrinsic pathway inhibitor (EPI), which is the inhibitor of the factor VIIa-tissue thromboplastin complex. EPI activity decreased from a median of 153% to 111% (p less than 0.001) with simvastatin treatment and to 112% (p less than 0.001) on the combined regimen. EPI activity was significantly correlated with LDL cholesterol (r = 0.78), total cholesterol (r = 0.77), apo B (r = 0.65), and apo A-1 (r = 0.45). Multiple stepwise regression analysis showed that LDL cholesterol was the most important predictor of EPI activity, which suggests that a majority of EPI activity in plasma is associated with LDL. Moreover, the alteration in EPI activity was correlated closely with the corresponding alteration in LDL, which suggests a direct relation between a coagulation-inhibitor activity and a pharmaceutical lipid-related response.(ABSTRACT TRUNCATED AT 250 WORDS)