[Show abstract][Hide abstract] ABSTRACT: In this segment of a multicenter study, 36 hypercholesterolemic patients were randomly assigned to fenofibrate or placebo treatment to assess effects on plasma concentrations of lipoprotein cholesterol and triglyceride, high-density lipoprotein-cholesterol subfractions, and apolipoproteins E, B, Al, and All. All of these factors are of known or potential value in determining the patient's risk of arteriosclerosis. Observations were made during initial screening and placebo phases, a 24-week, double-blind treatment phase, and a subsequent 24-week, open-label fenofibrate phase. There were three possible expressions of fenofibrate efficacy. Changes in lipoprotein cholesterol and total triglyceride concentrations observed in these patients were very similar to those seen with the larger multicenter cohort: total triglyceride levels decreased 38 to 46 percent, low-density lipoprotein cholesterol levels decreased 13 to 20 percent, and high-density lipoprotein cholesterol levels increased 4 to 13 percent. Triglyceride concentrations were significantly reduced (p less than 0.01) in very low-density lipoprotein (50 to 56 percent, similar to those of total triglyceride and very low-density lipoprotein cholesterol), and in low-density lipoprotein cholesterol levels (17 to 21 percent). A slight but statistically insignificant decrease in high-density lipoprotein triglyceride was observed (9 to 15 percent). High-density lipoprotein2 cholesterol levels did not change significantly, whereas high-density lipoprotein3 cholesterol levels increased 8 to 16 percent, accounting for all of the increase in high-density lipoprotein cholesterol. Apoprotein All levels increased significantly (13 to 20 percent) whereas those of apolipoprotein Al did not, consistent with an increase in high-density lipoprotein3 levels, where apolipoprotein All is more abundant relative to apolipoprotein Al than in high-density lipoprotein2. Apolipoprotein B levels decreased 20 to 26 percent and those of apolipoprotein E went from 29 to 34 percent, relative to the 16 to 20 percent decreases in very low-density lipoprotein and low-density lipoprotein triglyceride and cholesterol levels. Five patients with combined elevations of triglyceride and low-density lipoprotein cholesterol treated with fenofibrate, had reductions primarily in triglyceride, total apolipoprotein E (50 percent reduction), and apolipoprotein B (18 percent) levels. High-density lipoprotein3 cholesterol levels increased 19 percent and high-density lipoprotein2 cholesterol levels were unchanged. Low-density lipoprotein cholesterol levels declined slightly in four patients and a slight rise was observed in a fifth patient.(ABSTRACT TRUNCATED AT 400 WORDS)
No preview · Article · Dec 1987 · The American Journal of Medicine
[Show abstract][Hide abstract] ABSTRACT: To minimize the cutaneous flushing symptoms associated with niacin use, a time-release capsule form of niacin has been formulated. Thus study compares the effects of time-release niacin with those of unmodified niacin on lipoprotein lipids, including HDL2 and HDL3, apoproteins A-I and A-II, clinical chemistries, symptomatic side effects, and adherence to the medication regimen. Seventy-one primarily hypercholesterolemic subjects were randomized to either unmodified niacin or time-release niacin and took medication for a six-month period. The two groups were closely matched on anthropomorphic and lipid variables. Adherence to the therapeutic regimen at a dose of 1.5 g/d in the first month of treatment was similar in the two groups. Thereafter, at a dose of 3.0 g/d, adherence was in excess of 90% among subjects taking unmodified niacin but only 64% among those taking time-release niacin, chiefly because of aggravated gastrointestinal symptoms; cutaneous flushing side effects, however, were slightly less common with time-release niacin. At these levels of adherence, LDL cholesterol (C) was reduced 21% by unmodified niacin and 13% by the time release form. Plasma total triglyceride was reduced more with unmodified niacin (27%) than with time-release niacin (8% maximum), and HDL-C and HDL2-C were increased significantly with unmodified niacin (26% and 36%) and were not significantly changed by time-release niacin. Increased to a similar degree on both regimens were HDL3-C (∼35%) and apoA-I (∼12%). ApoA-II was not affected by either drug regimen. There were no differences in the effects of the two regimens on clinical chemistry tests except for slightly higher SGOT and alkaline phosphatase levels in the time-release group. We conclude that unmodified niacin may be preferable in initiating therapy for hyperlipidemia, particularly in subjects with combined elevations of triglyceride and cholesterol, but that time-release niacin may be of value in subjects with severe flushing symptoms and hypercholesterolemia as the primary disorder. The mechanism whereby niacin lowers triglyceride and raises HDL appears to differ from the mechanism of LDL cholesterol lowering, as do the mechanisms increasing HDL2 and HDL3 cholesterol. The two forms of niacin can serve as probes in studying lipoprotein interrelationships.