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.


METHODS
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.
Insull
W
W
Lipid Research Clinic, Baylor College of Medicine, Methodist Hospital, Houston.
Black
D
D
Dujovne
C
C
Hosking
J D
JD
Hunninghake
D
D
Keilson
L
L
Knopp
R
R
McKenney
J
J
Stein
E
E
Troendle
A J
AJ
D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D004311:Double-Blind Method; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D001057:Apolipoproteins E; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008055:Lipids; D000077340:Fluvastatin