Patients with familial hypercholesterolaemia (FH) respond poorly to dietary control of cholesterol levels. The use of medication, in particular HMG CoA reductase inhibitors such as simvastatin, is necessary to lower total and LDL cholesterol. FH is furthermore characterised by increased fibrinogen levels, one of the most important risk factors for CHD and stroke. The aim of this study was to investigate the effect of simvastatin on plasma fibrinogen levels and the balance between the formation and dissolution of blood clots. Twenty-seven genetically confirmed FH patients were included in the study. All subjects had been on a cholesterol lowering diet for 8 weeks prior to the commencement of the treatment phase. Subjects were prescribed 10mg simvastatin daily for 4 weeks, blood sam-pies were taken and the efficacy of treatment evaluated before dosage adjustment to either 10mg or 20 mg daily for a further 4 weeks. Treatment was evaluated and dosage adjustments were made before the final 6 week treatment period. The main results are summarised in the Table below: Men Women Baseline End Baseline End TC(mmol/L) 9.32(2.27) 6.90(1.56) 9.80(1.34) 7.62(0.81) Fibrinogen (g/L) 2.90(0.76) 3.21(0.79) 3.39(0.89) 3.37(0.68) TAT/PAP ratio 7.29(2.95) 6.20(3.22) 5.66(6.60) 4.02(2.18) Serum total and LDL cholesterol levels were significantly lowered in both men and women. Plasma fibrinogen increased significantly in men but not in women. The TAT/PAP ratios an indicator of the haemostatic balance, displayed a trend towards a more profibrinolytic state, indicating a possible compensatory adjustment or an additional beneficial effect of simvastatin. Simvastatin treatment was associated with a change in the coagulation profile in men of this study group. The clinical significance of the observed effects on total CHD risk should be investigated in more detail. © Pearson Professional Ltd 1996.