An extended-release (ER) formulation of fluvastatin 80 mg has been developed for once-daily treatment of primary hypercholesterolemia in patients who require fluvastatin dosages of > 40 mg/day. The study aimed to determine the efficacy and safety of the new formulation and to assess the dose response over the range of 40 to 160 mg/day. After a 4-week placebo/dietary run-in period, 123 patients with primary hypercholesterolemia (Fredrickson type IIa/IIb) were randomized to receive fluvastatin 40, 80, or 160 mg/day for 6 weeks. The 40 mg/day dosage was administered as the marketed immediate-release (IR) capsule and the 80 mg/day dosage as 1 80-mg ER tablet. Patients receiving 160 mg/day were administered 80 mg/day (1 ER tablet) for the first 2 weeks, followed by 160 mg/day (2 ER tablets) for the remainder of the study. All doses were administered once daily at bedtime. The results showed a linear dose-response relation. Doubling the fluvastatin dosage resulted in a 6% greater mean percent reduction in low-density lipoprotein cholesterol (40 mg IR -29%; 80 mg ER -35%; 160 mg ER -41%). In the 160-mg ER group, 62% of patients achieved > or = 40% reductions in low-density lipoprotein cholesterol compared with 32% and 10% of patients in the 80-mg ER and 40-mg IR groups, respectively. Dose ordering of the response was also observed for the other lipid parameters. Fluvastatin ER was well tolerated. Thus, the new ER formulation of fluvastatin was effective and well tolerated in the once-daily treatment of primary hypercholesterolemia.