Effects of coadministered extended-release niacin/laropiprant and simvastatin on lipoprotein subclasses in patients with dyslipidemia

J Clin Lipidol. 2012 May-Jun;6(3):235-43. doi: 10.1016/j.jacl.2011.11.004. Epub 2011 Dec 3.

Abstract

Background: The use of extended-release niacin and the prostaglandin D₂ receptor antagonist laropiprant (ERN/LRPT) reduces niacin-induced flushing in patients while preserving its lipid-modifying effects.

Objective: This predefined exploratory analysis examined the individual and combined effects of ERN/LRPT and simvastatin (SIM) on lipoprotein subclasses.

Methods: This double-blind study randomized 1398 dyslipidemic patients equally to ERN/LRPT 1 g/20 mg, SIM (10, 20, or 40 mg), or ERN/LRPT 1 g/20 mg + SIM (10, 20, or 40 mg) once daily for 4 weeks. At week 5, doses were doubled, except SIM 40 mg (unchanged) and ERN/LRPT 1 g/20 mg + SIM 40 mg (switched to ERN/LRPT 2 g/40 mg + SIM 40 mg). Cholesterol associated with lipoprotein subclasses was quantified by vertical auto profile II (VAP II).

Results: ERN/LRPT + SIM and SIM alone lowered LDL-C 1 and 3, whereas the effects were variable for ERN/LRPT; all three treatments increased LDL-C 4. ERN/LRPT + SIM and ERN/LRPT raised HDL-C 2 and 3, with greater relative percent changes in HDL 2 than HDL 3. ERN/LRPT + SIM for 12 weeks produced substantial reductions in IDL-C, which was additive compared with each monotherapy.

Conclusion: Coadministered ERN/LRPT + SIM produced marked reductions in atherogenic lipoproteins, with the greatest effect on IDL-C, and increases in protective HDL subclasses.

Trial registration: ClinicalTrials.gov NCT00269217.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Double-Blind Method
  • Dyslipidemias / drug therapy*
  • Female
  • Humans
  • Hypolipidemic Agents / administration & dosage*
  • Indoles / administration & dosage*
  • Male
  • Middle Aged
  • Niacin / administration & dosage*
  • Placebo Effect
  • Simvastatin / administration & dosage*
  • Young Adult

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hypolipidemic Agents
  • Indoles
  • MK-0524
  • Niacin
  • Simvastatin

Associated data

  • ClinicalTrials.gov/NCT00269217