The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia.

Abstract

OBJECTIVES: Nicotinic acid, an effective drug for treatment of combined hyperlipidaemia, is often not tolerated because of side-effects. Acipimox is a nicotinic acid like lipid lowering drug with less side-effects. We studied whether the addition of acipimox to simvastatin improves the lipid profile in patients with a combined hyperlipidaemia. DESIGN: Randomized double-blind placebo controlled crossover trial. SETTING: Outpatient lipid clinic of a tertiary referral centre. SUBJECTS: Eighteen patients with combined hyperlipidaemia treated with diet and 20-40 mg simvastatin for at least 3 months. INTERVENTION: Acipimox in a daily dose of 3 x 250 mg for 12 weeks. MAIN OUTCOME MEASURES: Effects on the concentration of LDLc, TG, HDLc, Lp(a) and Apolipoprotein B, as well as on LDL-size and LDL-resistance to oxidative modification. RESULTS: Acipimox reduced Lp(a) levels by 8% (P < 0.05). A substantial but not statistically significant change in TG (-32%) and HDLc (+6%) levels was seen. All patients were found to have small dense LDL, with a size of 229 +/- 4 A. LDL size and the resistance to oxidation, reflected in the lag phase during in vitro oxidation, were not affected by the addition of acipimox. In a subgroup of 8 patients with the most severe hypertriglyceridaemia (baseline TG < 4 mmol L- [1]), acipimox induced a significant increase in HDLc (+15%, P < 0.01). The effects on TG (-41%), LDLc (-10%) and lag phase (+17%) were also more pronounced than in the group with a lower baseline TG, but non of these changes reached the level of significance. CONCLUSIONS: Adding acipimox to simvastatin reduced Lp(a) and substantially but not significantly lowered TG. However, in patients with the highest TG levels, HDLc was also significantly improved.