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 safety of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin in hypercholesterolemic patients already receiving probucol. All of the participants had hypercholesterolemia. i.e. serum total cholesterol > or = 220 mg/dl, despite administration 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 evaluated for safety, and 22 were evaluated for efficacy. The addition of fluvastatin to the probucol regimen produced a significant further reduction in serum total and low-density lipoprotein cholesterol concentrations (of 18 and 20%, respectively; p < 0.001); these effects were fully established within 4 weeks of treatment and were maintained throughout the treatment. Fluvastatin did not affect the serum high-density lipoprotein cholesterol concentration. Fluvastatin treatment decreased serum triglyceride concentrations slightly in all patients (not significant); in patients with hypertriglyceridemia, triglyceride levels were decreased significantly by 34% (p < 0.01; serum triglycerides > or = 150 mg/dl). In addition, fluvastatin significantly decreased serum apolipoprotein B, C-II, C-III and E levels, whereas serum apolipoprotein A-I and A-II levels were unaffected. One patient complained of slight abdominal discomfort during fluvastatin administration, but relationship to fluvastatin remains unclear. One patient had slight elevation of the serum alanine aminotransferase level, and another patient had an elevated gamma-glutamyl transferase level. The addition of fluvastatin to probucol treatment can be considered to be an effective and well tolerated treatment in hypercholesterolemic patients.
Sasaki
S
S
Second Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Nakagawa
M
M
Nakata
T
T
Endo
N
N
Miyao
K
K
Kitamura
K
K
Fukuyama
M
M
Kitani
T
T
Yamada
C
C
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001053:Apolipoproteins / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D014280:Triglycerides; D000077340:Fluvastatin; D002784:Cholesterol; D011341:Probucol