EFFICACY AND SAFETY OF HIGH-DOSE FLUVASTATIN IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA

The efficacy and safety of the HMG CoA reductase inhibitor fluvastatin have been evaluated in a double blind study in 52 patients with famil ial hypercholesterolaemia. A standard AHA Phase II lipid lowering diet was prescribed throughout the study. After 6 weeks of a single blind dosage stabilisation period, in which patients received fluvastatin 40 mg qPM, patients were randomly allocated to one of two double blind t reatment groups: group A (n = 24) received fluvastatin 20 mg b. d. for 12 weeks and fluvastatin 20 mg AM + 40 mg PM for an additional 12 wee ks; Group B (n = 28) received fluvastatin 40 mg qPM during the entire study. Safety and tolerability were evaluated by the analysis of bioch emical and haematological parameters, and ophthalmological and physica l examinations. Efficacy was analysed by the determination of plasma l ipids, lipoproteins and apoproteins. Fluvastatin 40 mg/d was associate d with up to a 27.4% decrease in LDL-C and a 9.6% increase in HDL-C co ncentrations. Increasing the dose of fluvastatin from 20 mg b. d. to 6 0 mg per day in Group A was associated with a 7.1% decrease in LDL-C, a 12.1% increase of HDL-C and a 12.8% decrease in the LDL-C/HDL-C rati o. In comparison with Group B (40 mg qPM) LDL-C, HDL-C and the LDL-C/H DL-C ratio in Group A (60 mg) differed by -8.9%, 6.6% and -12%, respec tively. During treatment with 40 mg qPM, one patient developed an asym ptomatic but notable elevation of CK to 1823 U/l (normal range 0-100 U /l) that was caused by strenuous exercise. No other notable biochemica l or haematological abnormalities were recorded. It is concluded that in patients with heterozygous FH the increase of fluvastatin from 40 t o 60 mg/d provided an additional significant effect on plasma LDL-C an d HDL-C levels and in the LDL-C/HDL-C ratio, without producing any del eterious effect.