Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia

Am J Cardiol. 2008 Mar 1;101(5):625-30. doi: 10.1016/j.amjcard.2007.10.023. Epub 2007 Dec 21.


Niacin (nicotinic acid) is not optimally used mainly because of flushing, a process mediated primarily by prostaglandin D(2), which leads to poor patient compliance and suboptimal dosing. This phase II dose-ranging study was designed to assess whether the prostaglandin D(2) receptor 1 antagonist laropiprant (LRPT; MK-0524) would (1) reduce extended-release niacin (ERN)-induced flushing in dyslipidemic patients and (2) support a novel accelerated ERN dosing paradigm: initiating ERN at 1 g and advancing rapidly to 2 g. In part A of the study, 154 dyslipidemic patients were randomized to LRPT 150 mg/day or placebo in a 9-week, 2-period crossover study. Patients who completed part A (n = 122) entered part B (after a 2-week washout), together with additional patients who entered part B directly (n = 290). Part B patients were randomized to placebo, ERN 1 g (Niaspan, no previous titration), or ERN 1 g coadministered with LRPT 18.75, 37.5, 75, or 150 mg for 4 weeks, with doubling of the respective doses for the remaining 4 weeks. Patients treated with LRPT plus ERN experienced significantly less ERN-induced flushing than those treated with ERN alone during the initiation of treatment (ERN 1 g, week 1) and the maintenance treatment (ERN 1 to 2 g, weeks 2 to 8). All doses of LRPT were maximally effective in inhibiting niacin-induced flushing. LRPT did not alter the beneficial lipid effects of ERN. LRPT plus ERN was well tolerated. In conclusion, the significant reduction in ERN-induced flushing provided by LRPT plus ERN supports an accelerated ERN dose-advancement paradigm to achieve rapidly a 2-g dose in dyslipidemic patients.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Creatine Kinase / blood
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Dyslipidemias / drug therapy
  • Female
  • Flushing / chemically induced*
  • Flushing / prevention & control*
  • Humans
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / adverse effects*
  • Indoles / administration & dosage*
  • Male
  • Middle Aged
  • Niacin / administration & dosage
  • Niacin / adverse effects*
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Prostaglandin / antagonists & inhibitors


  • Delayed-Action Preparations
  • Hypolipidemic Agents
  • Indoles
  • MK-0524
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Niacin
  • Creatine Kinase
  • prostaglandin D2 receptor