BACKGROUND: Inhibitors of hydroxymethylglutaryl co-
enzyme A
reductase are widely used for the treatment of
hypercholesterolemia. Physicians and third-party payers need an accurate measure of their relative potency and hypolipidemic efficacy. We have therefore compared
simvastatin against
fluvastatin, the newest member of this class. METHODS AND RESULTS: One hundred fifty-eight hypercholesterolemic patients in seven United States
lipid clinics participated in this balanced double-blind incomplete block study. After a placebo-diet run-in period, patients received treatment with active
drug for three consecutive 5-week periods, with measurement of
lipids in a NHLBI-CDC standardized central laboratory at the end of each period. Each patient was randomly assigned to three of the following five treatments:
simvastatin 5 mg, 10 mg, and 20 mg and
fluvastatin 20 mg and 40 mg. The mean percent reductions in
low density lipoprotein cholesterol from baseline were 21, 27, 32, 16, and 23 respectively. The
simvastatin/
fluvastatin milligram potency ratio was 6.8 (95% CI, 5.3-9.3). At the same 20 mg dose,
simvastatin produced an effect on
LDL cholesterol approximately double that of
fluvastatin and resulted in 46% of patients achieving their National
Cholesterol Education Program
low density lipoprotein cholesterol target levels, compared to 12% for
fluvastatin. CONCLUSIONS:
Fluvastatin at its maximal dose of 40 mg daily is approximately equivalent to
simvastatin 5 mg daily. Higher doses of
simvastatin are considerably more effective in the treatment of primary
hypercholesterolemia.