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

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.