Short-term effects of extended-release niacin with and without the addition of laropiprant on endothelial function in individuals with low HDL-C: a randomized, controlled crossover trial

Clin Ther. 2014 Jun 1;36(6):961-6. doi: 10.1016/j.clinthera.2014.03.012. Epub 2014 Apr 24.


Background: Reduced plasma concentration of high-density lipoprotein cholesterol (HDL-C) is associated with vulnerability to oxidative stress and propensity to endothelial dysfunction. Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong anti-inflammatory and antioxidative effects, as well as induces immediate production of prostaglandin D2, leading to endothelial vasodilation.

Objective: This study investigated the short-term effects of extended-release niacin (ERN) administered with or without the prostaglandin D2 receptor antagonist laropiprant on endothelial function in patients with low HDL-C.

Methods: Asymptomatic men and women aged between 20 and 60 years who had plasma HDL-C levels <40 mg/dL were treated with ERN monotherapy 1 g/d or ERN/laropiprant 1 g/20 mg (ERN/LRP) in a crossover study design. The sequence of treatments was decided by simple randomization. Plasma samples and flow-mediated dilation (FMD) of the brachial artery were obtained at baseline, day 7 of treatment period 1, day 7 of washout, and day 7 of treatment period 2.

Results: Eighteen patients were enrolled (mean [SD] age, 42 [17] years; 11 men). Triglyceride levels decreased by 4% and 3%, and HDL size decreased by 5.8% and 6.2%, with ERN and ERN/LRP, respectively (both, P < 0.05). There were no changes in HDL-C levels or in cholesteryl esterase transfer protein activity with either treatment. The median increases in FMD were 4.5% and 4.1% with ERN and ERN/LRP, which receded after washout. On intergroup analysis, there were no differences with respect to variation in plasma HDL-C, triglycerides, C-reactive protein, direct bilirubin, or FMD.

Conclusions: In these patients, the addition of laropiprant did not influence the effects of niacin on endothelial function. Based on these findings, short-term niacin treatment might improve endothelial function in patients with low HDL-C levels. identifier: NCT01942291.

Keywords: HDL; endothelial function; laropiprant; niacin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cholesterol, HDL / blood
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Double-Blind Method
  • Dyslipidemias / drug therapy*
  • Endothelium, Vascular / drug effects*
  • Female
  • Humans
  • Hypolipidemic Agents / therapeutic use
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Niacin / administration & dosage
  • Niacin / pharmacology*
  • Vasodilation / drug effects
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology*


  • Cholesterol, HDL
  • Delayed-Action Preparations
  • Hypolipidemic Agents
  • Indoles
  • MK-0524
  • Vasodilator Agents
  • Niacin

Associated data