EFFICACY AND SAFETY OF THE 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE INHIBITOR FLUVASTATIN IN HYPERLIPIDEMIC PATIENTS TREATED WITH PROBUCOL

The objective of this open trial was to investigate the efficacy and s afety of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin in hypercholesterolemic patients already receiv ing probucol, All of the participants had hypercholesterolemia. i.e. s erum total cholesterol greater than or equal to 220 mg/dl, despite adm inistration of probucol, 500 mg/day, for more than 4 weeks, After this , fluvastatin, 30 mg/day, was added to probucol treatment for 12 weeks , Twenty-seven patients were recruited into this study; all were evalu ated for safety, and 22 were evaluated for efficacy. The addition of f luvastatin to the probucol regimen produced a significant further redu ction in serum total and low-density lipoprotein cholesterol concentra tions (of 18 and 20%, respectively; p < 0.001); these effects were ful ly established within 4 weeks of treatment and were maintained through out the treatment, Fluvastatin did not affect the serum high-density l ipoprotein cholesterol concentration. Fluvastatin treatment decreased serum triglyceride concentrations slightly in all patients (not signif icant); in patients with hypertriglyceridemia, triglyceride levels wer e decreased significantly by 34% (p < 0.01; serum triglycerides greate r than or equal to 150 mg/dl). In addition, fluvastatin significantly decreased serum apolipoprotein B, C-II, C-III and E levels, whereas se rum apolipoprotein A-I and A-II levels were unaffected. One patient co mplained of slight abdominal discomfort during fluvastatin administrat ion, but relationship to fluvastatin remains unclear. One patient had slight elevation of the serum alanine aminotransferase level, and anot her patient had an elevated gamma-glutamyl transferase level. The addi tion of fluvastatin to probucol treatment can be considered to be an e ffective and well tolerated treatment in hypercholesterolemic patients .