COMBINED TREATMENT WITH SIMVASTATIN AND ACIPIMOX IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA WITH ELEVATED LIPOPROTEIN(A)

Thirty-three patients heterozygous for familial hypercholesterolemia ( FH) with elevated serum lipoprotein(a) [Lp(a)] (median and range, 46 a nd 22-97 mg dl-1) were treated for 24 weeks with a low-fat diet and si mvastatin (40 mg daily). The nicotinic acid derivative acipimox was ad ded from week 6 to week 18 in randomly allocated doses of 0.75 or 1.2 g daily. Simvastatin monotherapy significantly decreased serum LDL cho lesterol, apolipoprotein (apo) B and triglycerides by 45%, 37%, and 16 %, respectively, while HDL cholesterol and apo A-I were significantly increased by 5% and 11%, respectively. Addition of acipimox caused fur ther significant decreases in LDL cholesterol, apo B, and triglyceride s to a total of 50%, 44%, and 28%, respectively, and increases in HDL cholesterol and apo A-I by 15% and 13%, respectively. Changes in lipop rotein variables were similar on both acipimox doses. Serum Lp(a) leve ls were not affected by simvastatin monotherapy or by the concomitant use of acipimox. Changes in lipoprotein parameters were not related to apo E phenotype, except for the increase in HDL cholesterol during co mbination therapy, which was significantly higher in subjects homo- or heterozygous for apo E4 than in apo E3 homozygotes. We conclude that acipimox further improves the overall lipoprotein pattern, without, ho wever, influencing serum Lp(a) levels, in patients with FH and elevate d Lp(a) treated with simvastatin, and that safety parameters are not n egatively affected by this new form of combination therapy.