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Effects of probucol on plasma cholesterol, high and low density lipoprotein cholesterol, and apolipoproteins A1 and A2 in adults with primary familial hypercholesterolemia

Authors
Journal
Metabolism
0026-0495
Publisher
Elsevier
Publication Date
Volume
29
Issue
10
Identifiers
DOI: 10.1016/0026-0495(80)90039-6
Disciplines
  • Biology
  • Design
  • Medicine

Abstract

Abstract This double-blind crossover study was designed to assess the safety, utility, and effectiveness of probucol (1000 mg/day) as an agent for reduction of total and low density lipoprotein plasma cholesterol (C-LDL) in 19 adults with primary familial hypercholesterolemia. The study was also designed to evaluate the effects of probucol on high density lipoprotein cholesterol (C-HDL) and its two major apolipoproteins, Apo A1 and Apo A2. After stabilization on a diet that provided < 200 mg cholesterol/day with a P S ratio of 1.2:1, the subjects were randomized into the following drug-placebo sequences: 9 subjects received 24 wk of probucol followed by 24 wk of placebo, while 10 received 24 wk of placebo followed by 24 wk of probucol, with weight maintained ± 1 kg, and dietary cholesterol and P S intake stable. In all 19 subjects on probucol total plasma cholesterol was reduced 10.7% and C-LDL 8.4% beyond the effects of diet alone; plasma triglyceride, the ratio of C-HDL to Apo A1, and the ratio of Apo A1 Apo A2 were not significantly changed. In all 19 subjects, the C-LDL C-HDL ratio during probucol therapy was 22% higher than during placebo, with an overall 26% reduction in C-HDL on probucol as compared to placebo. In the group of 9 subjects, whose plasma C-HDL levels fell 19% on probucol, mean HDL apolipoprotein A1 (Apo A1) levels fell 6%, Apo A2 levels did not change. In the group of 10 subjects whose mean plasma C-HDL levels fell 30% on probucol, mean Apo A1 fell 34%, and Apo A2 fell 20%. The probucol was well tolerated, with mean adherence of 93%. Of the 19 subjects, the only drug-related side effects were diarrhea in two subjects, and fetid perspiration in another. The relevance of the simultaneous reduction in C-HDL in the face of a mean 8.4% reduction in C-LDL is unknown. Better long-term information about the prognostic significance for atherosclerotic disease of the reductions in C-HDL, Apo A1, and Apo A2 need to be obtained, in view of the inverse association of C-HDL with coronary heart disease.

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