Fluvastatin in familial hypercholesterolemia: a cohort analysis of the response to combination treatment.
A recent randomized, double-blind, double-dummy trial revealed differences in the response of patients with heterozygous familial hypercholesterolemia to combination therapy with the new, wholly synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor fluvastatin, 20 mg/day and then 40 mg/day, plus the fibric acid analogue bezafibrate, 400 mg/day, vs combination therapy with fluvastatin, 40 mg/day, plus the bile acid sequestrant (resin) cholestyramine, 8 g/day. The main purpose of the present cohort analysis was to determine whether these differences in lipid response were related to imbalances in the patients' prior responses to up to 42 weeks of fluvastatin monotherapy, 20 mg/day, 40 mg/day, and, in some patients, 60 mg/day, in 2 earlier studies. For the present analysis, we identified 18 patients in the fluvastatin plus bezafibrate group (cohort 1) and 16 patients in the fluvastatin plus cholestyramine group (cohort 2) for whom complete dose-response data were available for the full 56-week duration of all 3 studies. Subsets of 7 patients in cohort 1 and 8 patients in cohort 2 had received the 60 mg/day fluvastatin dose during a previous monotherapy study. In cohort 1, low density lipoprotein cholesterol (LDL-C) decreased by 19% with 20 mg/day fluvastatin, by 27% with 40 mg/day fluvastatin, by 31% with 20 mg/day fluvastatin plus bezafibrate, and by 35% with 40 mg/day fluvastatin plus bezafibrate, and the LDL-C/high density lipoprotein cholesterol (HDL-C) ratio had fallen by 46% at the end of combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Muratti
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EN
Division of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Peters
T K
TK
Leitersdorf
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E
D000328:Adult; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001629:Bezafibrate / Q000008:administration & dosage; D002792:Cholestyramine Resin / Q000008:administration & dosage; D015331:Cohort Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D000077340:Fluvastatin; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008055:Lipids; D008074:Lipoproteins; D002792:Cholestyramine Resin; D000077340:Fluvastatin; D001629:Bezafibrate