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 ha s been developed for once-daily treatment of primary hypercholesterolemia. Objective: The purpose of this study was to compare the lipid-lowering effi cacy and tolerability of fluvastatin ER (80 mg once daily) versus fluvastat in immediate-release (IR) (40 mg once or twice daily). Methods: Following a 4-week placebo/dietary run-in period, patients with pr imary hypercholesterolemia type IIa or IIb (low-density lipoprotein cholest erol [LDL-C] greater than or equal to 160 mg/dL and triglycerides [TG] less than or equal to 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 fluvast atin IR 40 mg BID for 24 weeks. Patients who had homozygous familial hyperc holesterolemia; type I, III, IV, V, or secondary hyperlipoproteinemia mia: 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 LD L-C, high-density lipoprotein cholesterol (HDL-C). TG, and total cholestero l (TC) were measured. Results: Of the 1183 patients enrolled, 695 were randomly assigned to treat ment-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 similar to 56 years and body mass index of 27 kg/m(2); 56.0% of patients (389/695) were female and 97.7% (679/695) were white. Flu vastatin ER 80 mg QPM lowered LDL-C levels significantly more than did fluv astatin IR 40 mg QPM (33.7% vs 24.4%; P < 0.001) and as effectively as fluv astatin IR 40 mg BID (33.9%). More than half of the patients administered f luvastatin ER 80 mg QPM and IR 40 mg BID achieved reductions in LDL-C level s of <greater than or equal to>35%; more than half of those administered fl uvastatin IR 40 mg QPM experienced reductions in LDL-C levels of greater th an or equal to 25%. The mean reductions in LDL:HDL ratio, TC, and apolipopr otein B levels in the fluvastatin ER 80 mg QPM group were significantly gre ater than the reductions in the IR 40 me 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 a nd musculoskeletal adverse events comparable to those in the LR 40 me QPM g roup. Conclusion: The ER 80-mg formulation of fluvastatin is effective and well t olerated as a once-daily starting and maintenance treatment for primary hyp ercholesterolemia.