Efficacy and safety of once-daily vs twice-daily dosing with fluvastatin, a synthetic reductase inhibitor, in primary hypercholesterolemia

Background: Fluvastatin sodium is a new entirely synthetic 3-hydroxy-3- methylglutaryl coenzyme A reductase inhibitor that may be an effective lipid- lowering agent in patients whose hyperlipidemia does not respond to dietary therapy. We conducted a study to evaluate the effects of fluvastatin on lipoprotein levels in subjects with primary hypercholesterolemia and to compare the efficacy and safety of two fluvastatin sodium dosing regimens; 20 mg once daily vs 10 mg twice daily. Design: We conducted a double-blind, placebo-controlled, multicenter trial involving 207 patients with low- density lipoprotein cholesterol levels of 4.15 mmol/L (160 mg/dL) or higher despite dietary intervention and with triglyceride levels of 3.38 mmol/L or lower. Three parallel treatment groups received 6 weeks of treatment with 20 mg of fluvastatin sodium once daily, 10 mg of fluvastatin sodium twice daily, or a placebo. Results: Total cholesterol and low-density lipoprotein cholesterol levels were reduced from baseline by 16% and 22%, respectively, with 20 mg of fluvastatin sodium once daily (P<.001) and by 17% and 23%, respectively, with 10 mg of fluvastatin sodium twice daily (P<.001). Fluvastatin was well tolerated, and there were no serious clinical or biochemical adverse events ascribable to the drug. Conclusions: Fluvastatin therapy demonstrated excellent short-term safety and efficacy in reducing total and low-density lipoprotein cholesterol levels in patients with primary hypercholesterolemia. Fluvastatin sodium, the first totally synthetic 3- hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to be used in clinical trials, appears to be both effective and well tolerated at 20 mg/d, given in either a single or divided dose.