Effect of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the haemostatic balance of familial hypercholesterolaemic subjects

Background: Previous studies have shown that the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce cardiovascular mortality and all-cause mortality in primary and secondary prevention trials. Studies on the effect of HMG-CoA reductase inhibitors on plasma fibrinogen levels have yielded conflicting results. Objective: Our objective was to study the treatment effects of the HMG-CoA reductase inhibitor, simvastatin, on the haemostatic balance in 29 unrelated 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 simvastatin 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 accompanied by compensatory profibrinolytic changes in the ratio of thrombin/antithrombin 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 lipid lowering treatment with simvastatin, is accompanied by compensatory profibrinolytic changes in men and that the haemostatic system in men and women could be influenced via different mechanisms.