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 effecti ve lipid-lowering agent in patients whose hyperlipidemia does not resp ond to dietary therapy. We conducted a study to evaluate the effects o f fluvastatin on lipoprotein levels in subjects with primary hyperehol esterolemia 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 in volving 207 patients with low-density lipoprotein cholesterol levels o f 4.15 mmol/L (160 mg/dL) or higher despite dietary intervention and w ith triglyceride levels of 3.38 mmol/L or lower. Three parallel treatm ent groups received 6 weeks of treatment with 20 mg of fluvastatin sod ium once daily, 10 mg of fluvastatin sodium twice daily, or a placebo. Results: Total cholesterol and low-density lipoprotein cholesterol le vels were reduced from baseline by 16% and 22%, respectively, with 20 mg of fluvastatin sodium once daily (P<.001) and by 17% and 23%, respe ctively, with 10 mg of fluvastatin sodium twice daily (P<.001). Fluvas tatin was well tolerated, and there were no serious clinical or bioche mical adverse events ascribable to the drug. Conclusions: Fluvastatin therapy demonstrated excellent short-term safety and efficacy in reduc ing total and low-density lipoprotein cholesterol levels in patients w ith primary hypercholesterolemia. Fluvastatin sodium, the first totall y synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to be used in clinical trials, appears to be both effective and well t olerated at 20 mg/d, given in either a single or divided dose.