Comparison of the efficacy and tolerability of fluvastatin extended-release and immediate-release formulations in the treatment of primary hypercholesterolemia: a randomized trial.

BACKGROUND: A new extended-release (ER) formulation of fluvastatin 80 mg has been developed for once-daily treatment of primary hypercholesterolemia.

OBJECTIVE: The purpose of this study was to compare the lipid-lowering efficacy and tolerability of fluvastatin ER (80 mg once daily) versus fluvastatin immediate-release (IR) (40 mg once or twice daily).

METHODS: Following a 4-week placebo/dietary run-in period, patients with primary hypercholesterolemia type IIa or IIb (low-density lipoprotein cholesterol ILDL-C] > or = 160 mg/dL and triglycerides [TG] < or = 400 mg/dL) were randomized (2:1:1) to receive fluvastatin ER 80 mg once daily at bedtime (QPM), fluvastatin IR 40 mg QPM, or fluvastatin IR 40 mg BID for 24 weeks. Patients who had homozygous familial hypercholesterolemia; type I, III, IV, V, or secondary hyperlipoproteinemia; diabetes; or evidence of liver or renal impairment were excluded. At weeks 0, 2, 4, 8, 12, 16, 20, and 24 of the active-treatment period, levels of LDL-C, high-density lipoprotein cholesterol (HDL-C), TG, and total cholesterol (TC) were measured.

RESULTS: Of the 1183 patients enrolled, 695 were randomly assigned to treatment--346 to fluvastatin ER 80 mg QPM, 174 to fluvastatin IR 40 mg QPM, and 175 to fluvastatin IR 40 mg BID. Patients were well matched between groups, with a mean age of approximately 56 years and body mass index of 27 kg/m2; 56.0% of patients (389/695) were female and 97.7% (679/695) were white. Fluvastatin ER 80 mg QPM lowered LDL-C levels significantly more than did fluvastatin IR 40 mg QPM (33.7% vs 24.4%; P < 0.001) and as effectively as fluvastatin IR 40 mg BID (33.9%). More than half of the patients administered fluvastatin ER 80 mg QPM and IR 40 mg BID achieved reductions in LDL-C levels of > or = 35%; more than half of those administered fluvastatin IR 40 mg QPM experienced reductions in LDL-C levels of > or = 25%. The mean reductions in LDL:HDL ratio, TC, and apolipoprotein B levels in the fluvastatin ER 80 mg QPM group were significantly greater than the reductions in the IR 40 mg QPM group (P < 0.001). In patients with mixed dyslipidemia, fluvastatin ER 80 mg reduced triglycerides by 21.8% (median 28%) and increased HDL-C by 14.5%. Fluvastatin ER 80 mg QPM was well tolerated, with incidences of clinically notable elevations in alanine aminotransferase, aspartate aminotransferase, and creatine kinase levels and musculoskeletal adverse events comparable to those in the IR 40 mg QPM group.

CONCLUSION: The ER 80-mg formulation of fluvastatin is effective and well tolerated as a once-daily starting and maintenance treatment for primary hypercholesterolemia.