EFFECT OF SIMVASTATIN, A 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE INHIBITOR, ON THE HEMOSTATIC BALANCE OF FAMILIAL HYPERCHOLESTEROLEMIC SUBJECTS

Background: Previous studies have shown that the use of 3-hydroxy-3-me thylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce cardiova scular mortality and all-cause mortality in primary and secondary prev ention trials. Studies on the effect of HMG-CoA reductase inhibitors o n plasma fibrinogen levels have yielded conflicting results. Objective : Our objective was to study the treatment effects of the HMG-CoA redu ctase inhibitor, simvastatin, on the haemostatic balance in 29 unrelat ed familial hypercholesterolaemic patients. Subjects: Twenty nine diet stable familial hypercholesterolaemic patients, 12 men and 17 women, were treated with 10 mg simvastatin for 4 weeks and then with 20 mg si mvastatin for 10 weeks. Various coagulation and fibrinolytic variables were measured. Results: Simvastatin treatment significantly increased plasma fibrinogen levels in men (2.75 [0.75] g/L to 2.99 [0.60] g/L) but not in women. These increases in fibrinogen in men were accompanie d by compensatory profibrinolytic changes in the ratio of thrombin/ant ithrombin III complex to plasmin/alpha(2)antiplasmin complex, a marker of the haemostatic balance. Conclusion: This study provides evidence that possible negative changes in plasma fibrinogen, as a result of li pid lowering treatment with simvastatin, is accompanied by compensator y profibrinolytic changes in men and that the haemostatic system in me n and women could be influenced via different mechanisms.