FLUVASTATIN IN COMBINATION WITH OTHER LIPID-LOWERING AGENTS

Fluvastatin, a new synthetic inhibitor of HMGCoA (3-hydroxy-3-methylgl utaryl coenzyme A) reductase, has been studied in several models to ex amine its effects when used in combination with other lipid-modifying agents such as derivatives of fibric acid (bezafibrate), resins (chole styramine), and niacin. The combination of fluvastatin with bezafibrat e has been studied in a double-blind trial involving patients with wel l-documented familial hypercholesterolaemia. Fluvastatin 40 mg/day, co mbined with either bezafibrate 400 mg/day or cholestyramine 8 g/day, r esulted in reductions in levels of low-density lipoprotein cholesterol (LDL-C), these being indistinguishable between the groups; however, s ignificantly greater increases in levels of high-density lipoprotein c holesterol (21.3%) and reductions in levels of triglycerides (25.1%) w ere seen with the fluvastatin-bezafibrate combination.(1) No notable i ncreases were seen in levels of serum creatine kinase, aspartate amino transferase, or alanine aminotransferase, and no cases of myopathy wer e observed. In a study model that examined low-dose combinations of fl uvastatin with cholestyramine, reductions in levels of LDL-C of 15.8% and 19.3% were seen with fluvastatin 10 mg and 20 mg, respectively.(2) After an 8-week interval in which a daily dosage of cholestyramine 8 g was added, from baseline, reductions of 26.3% in the 10 mg fluvastat in-cholestyramine group and 31.2% in the 20 mg fluvastatin-cholestyram ine group were observed, whereas the placebo-cholestyramine group disp layed a reduction of 14.9%.(2) Doubling the resin dosage to 16 g/day f or the final 8 weeks of the study provided little additional benefit. Myotoxicity has been observed when lovastatin is coadministered with n iacin, and so the combination of niacin with fluvastatin has also been studied to examine the possibility of this effect occurring.(3) Patie nts were randomised to either fluvastatin 20 mg or placebo for 6 weeks , after which time open-label niacin was administered to all patients and titrated to a final dosage of 3 g/day. After 6 weeks, fluvastatin produced a 20.8% reduction in LDL-C levels from baseline. When combine d with niacin, a 43.7% reduction was noted at the week 15 endpoint, ag ainst the 26.5% reduction seen with niacin monotherapy The combination was well tolerated, with no reports of myopathy or of significant ele vations in creatine kinase or liver transaminase levels.(3) Combinatio ns of fluvastatin with a variety of other agents have been shown to ha ve significant effects on lipid profiles, with no evidence to date of clinically remarkable safety findings. Thus, the use of combination th erapies may result in optimal management of patients with moderately s evere hypercholesterolaemia and mixed dyslipidaemic profiles.