acipimox and Hyperlipoproteinemia-Type-IV

Serum and lipoprotein lipid levels, oral glucose tolerance and side-effects were compared in an open cross-over study of 31 non-diabetic patients with hypertriglyceridaemia (type II B and IV) before and after 6 weeks of treatment with nicotinic acid (3 g daily) and acipimox (0.75 g daily), a new nicotinic acid-like drug, respectively. Acipimox was about equally potent in reducing serum and VLDL lipid levels and in increasing HDL cholesterol levels. Acipimox had no significant negative effects on glucose metabolism measured by an oral glucose tolerance test compared with nicotinic acid, which decreased the late glucose tolerance as well as the area under the glucose curve (P less than 0.05 for the difference between the two treatments). The incidence and severity of flush or any other recorded side-effects was higher after nicotinic acid treatment than after acipimox. In addition, no effects on laboratory parameters such as liver enzymes and uric acid were seen after treatment with acipimox. The results of this study demonstrate that acipimox is a satisfactory alternative to nicotinic acid in patients with hypertriglyceridaemia.

Topics: Adult; Blood Glucose; Female; Glucose Tolerance Test; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Hypolipidemic Agents; Lipids; Male; Middle Aged; Niacin; Pyrazines

Two separate studies were carried out with acipimox, a new antilipolytic agent with long-lasting activity. First, in a randomized, double-blind, cross-over study a dose of 750 mg/day of acipimox versus placebo was employed for 60 days in 11 patients with type IV hyperlipoproteinemia. Mean plasma triglyceride levels were reduced after acipimox compared to placebo (434 +/- 60 vs 777 +/- 224 mg/dl, P less than 0.01). Serum total cholesterol fell also significantly after acipimox compared to placebo. No significant alteration was observed in the HDL2/HDL3 ratio or in the concentration or composition of the HDL subfractions. Six patients with severe hypertriglyceridemia (2 type IV and 4 type V) and low lipoprotein lipase (LPL) activity took part in a second, open study, lasting for 9 months. Acipimox was given at a dose of 750 mg/day for the first 6 months and 1200 mg/day for the last period. The response of serum total and VLDL triglycerides was inconsistent. HDL cholesterol was significantly raised (+33.3%) after 9 months of treatment due to changes of HDL2 and HDL3 cholesterol, phospholipid and protein concentrations. LPL activity was markedly reduced in adipose tissue at 9 months. No significant changes occurred in postheparin plasma LPL activity. In contrast, hepatic lipase activity showed a reduction of about 25% from 6 months of treatment onwards.

Topics: Adult; Cholesterol, HDL; Clinical Trials as Topic; Double-Blind Method; Humans; Hyperlipoproteinemia Type IV; Hyperlipoproteinemia Type V; Hypolipidemic Agents; Lipase; Lipoprotein Lipase; Lipoproteins, HDL; Male; Middle Aged; Phospholipids; Pyrazines; Random Allocation; Triglycerides

A multicenter study was carried out in 130 out-patients to assess the plasma lipid lowering activity of acipimox in type IIa, IIb and IV hyperlipoproteinemia. The study consisted of two periods, an 8-week randomized, double-blind comparison of active drug versus placebo and a 16-week open follow-up with acipimox (400 mg and 250 mg t.i.d., respectively, in type II and IV patients). During the double-blind phase acipimox, compared to placebo, showed a highly significant triglyceride lowering effect in type IV patients (-43% vs. +4%, P less than 0.01), while reducing plasma cholesterol significantly in type II patients (-7% vs. -3%, P less than 0.05). Further reductions in plasma lipids were obtained in both types of hyperlipoproteinemia after the 16-week follow-up. In type II patients, total cholesterol fell by 9% in the former acipimox group and 17% in the former placebo group, whereas a 34% reduction in triglycerides was found in type IV patients previously treated with placebo. Treatment had to be discontinued in 4 patients during the double-blind phase and in 5 patients during follow-up, because of adverse events such as skin reactions and gastric disturbances. Statistical analysis of hematological and biochemical variables expressing safety did not show any significant change during treatment.

Topics: Adult; Aged; Cholesterol; Clinical Trials as Topic; Double-Blind Method; Female; Follow-Up Studies; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Hypolipidemic Agents; Lipids; Male; Middle Aged; Pyrazines; Triglycerides

Acipimox, an analogue of nicotinic acid, is a hypolipidemic drug with antilipolytic activity. Ten patients with type III and 10 with type IV hyperlipoproteinemia participated in a comparative open cross-over study of the effect of acipimox (750 mg/day) and clofibrate (2 g/day) on lipoproteins, apoliproproteins and postheparin lipase activities during 6 weeks. During acipimox treatment 2 type III patients complained of flushing, resulting in one drop-out. In the type III patients serum cholesterol decreased 30% (P less than 0.01) during treatment with acipimox and 24% (P less than 0.01) with clofibrate, and serum triglycerides 48% (P less than 0.01) and 34% (P less than 0.01), respectively. In the type IV patients serum cholesterol remained unchanged and serum triglycerides decreased 34% (P less than 0.05) and 35% (P less than 0.01), respectively. HDL cholesterol increased during treatment with both drugs in both groups between 6 and 15% (P less than 0.05) mainly due to a rise in HDL3 cholesterol (d greater than 1.100 g/ml). LDL cholesterol increased significantly during treatment with clofibrate, but not with acipimox. There were no or slight changes in the apoproteins A and B. Postheparin lipoprotein lipase increased during clofibrate treatment and hepatic lipase decreased during acipimox treatment. We concluded that acipimox in a dose of 750 mg/day has a similar hypolipidemic effect as 2 g clofibrate daily in type III and IV hyperlipoproteinemia.

Topics: Adult; Aged; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins A; Apolipoproteins B; Cholesterol; Clofibrate; Female; Humans; Hyperlipoproteinemia Type III; Hyperlipoproteinemia Type IV; Hypolipidemic Agents; Lipase; Lipoprotein Lipase; Lipoproteins; Male; Middle Aged; Pyrazines; Triglycerides

A 51-year-old male patient with histologically confirmed eruptive xanthomatosis is presented. Routine and special laboratory examinations showed complex disturbances of carbohydrate and lipid metabolism, the latter taking the form of classic hyperlipoproteinaemia type IV. Combined oral antilipaemic drugs including acipimox (methylpyrazine carboxylic acid analogue of nicotinic acid) and a low-fat diet resulted in regression of the skin symptoms and normalization of the serum lipid levels.

Topics: Combined Modality Therapy; Diet, Fat-Restricted; Humans; Hyperlipoproteinemia Type IV; Hypolipidemic Agents; Male; Middle Aged; Pyrazines; Skin; Xanthomatosis