High-dose fluvastatin and bezafibratecombination treatment for heterozygous familial hypercholesterolemia

This study assessed the long-term use of fluvastatin, alone or in combination with bezafibrate, in patients with severe familial hypercholesterolemia who, in a previous study, did not achieve target levels (European Atherosclerosis Society) of low density lipoprotein cholesterol (LDL-C) with fluvastatin at 60 mg/day plus bezafibrate 200 mg/day, with or without cholestyramine (CME) at 8 g/day. This open-label study comprised 3 periods: period I, 6 weeks of fluvastatin at 40 mg twice daily (at breakfast and at bedtime); period II, fluvastatin at 80 mg/day (40 mg at breakfast, 40 mg at bedtime), and bezafibrate at 200 mg/day (at lunchtime) for 6 weeks in patients not achieving LDL-C target levels; and period III, force-titration of fluvastatin to 80 mg/day (as in period II) and bezafibrate at 400 mg/day (slow release) in patients receiving combination treatment. Patients were excluded if, during the previous study, they had experienced a serious drug-related adverse event or deterioration in liver or kidney function (liver enzymes >3 times upper limit of normal). The standard physical and laboratory evaluations were performed at regular intervals. Lipid profiles were determined from 12-hour fasting blood samples. All adverse events occurring or worsening during the study, whether spontaneously reported or elicited by questioning, and regardless of relationship to study medication, were recorded. So far, data up to week 36 of this 88-week study indicate a progressive reduction of LDL-C levels from 300.0 ± 48.7 (baseline) to 205.3 ± 41.9 mg/dL (80 mg fluvastatin), 192.7 ± 24.8 mg/dL (80 mg fluvastatin plus 200 mg bezafibrate for 6 weeks), and 184.4 ± 28.2 mg/dL (80 mg fluvastatin plus 400 mg bezafibrate for 24 weeks). Similarly, the LDL-C:high density lipoprotein cholesterol ratio improved from 8.1 ± 2.1 to 4.5 ± 1.1. With this high-dose combination treatment, only 6 patients had LDL-C levels >200 mg/dl. During this period of the study, no adverse events were recorded and all medications were well tolerated. The compliance rate, as determined by capsule or tablet counting, was >92.7% for fluvastatin and >84.9% for bezafibrate. In conclusion, these results suggest that high-dose fluvastatin combined with bezafibrate is safe and effective in the treatment of patients with heterozygous familial hypercholesterolemia.