Tolerability and effects of high doses acipimox as additional lipid-lowering therapy in familial hypercholesterolemia.
BACKGROUND
Acipimox, a derivative of nicotinic acid, lowers serum lipid levels by reducing the production of very-low-density and low-density lipoproteins (LDL).


METHODS
We studied the additional lipid-lowering effect of high doses of acipimox in 12 patients with severe familial hypercholesterolemia (FH) who were on treatment with an HMG CoA reductase inhibitor, in some cases in combination with a resin.


RESULTS
There was a significant reduction in total serum cholesterol (-9%), LDL-cholesterol (-9%) and serum triglycerides (-21%) when the standard doses of acipimox (750 mg/day) was added to treatment with simvastatin (and a resin). However, higher doses had no further hypolipidemic effect. In concordance with the reduction of serum cholesterol and LDL-cholesterol there was a significant decrease in apolipoprotein (apo)-B (-11%). There was no change in HDL-cholesterol, apo-A1 and lipoprotein(a). Acipimox in high doses up to 2250 mg/d was well tolerated except for initial gastric complaints and of flushing; because of these side effects one patient dropped out of the study.


CONCLUSIONS
Acipimox in high doses, which were well tolerated, has no additional lowering effect on LDL-levels compared to the standard dose in patients with severe FH who are already treated with simvastatin.
Stuyt
P M
PM
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands. p.stuyt@aig.azn.nl
Kleinjans
H A
HA
Stalenhoef
A F
AF
D000328:Adult; D000368:Aged; D015243:Cholesterol, VLDL / Q000097:blood / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage*; D012449:Safety; D019821:Simvastatin / Q000627:therapeutic use*
D015243:Cholesterol, VLDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D011719:Pyrazines; D019821:Simvastatin; C027696:acipimox