Changes in lipoprotein particle number with ezetimibe/simvastatin coadministered with extended-release niacin in hyperlipidemic patients

J Am Heart Assoc. 2013 Aug 7;2(4):e000037. doi: 10.1161/JAHA.113.000037.


Background: Combination therapy with ezetimibe/simvastatin (E/S) and extended-release niacin (N) has been reported to be safe and efficacious in concomitantly reducing low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol in hyperlipidemic patients at high risk for atherosclerotic cardiovascular events. This analysis evaluated the effect of E/S coadministered with N on low-density lipoprotein particle number (LDL-P) and high-density lipoprotein particle number (HDL-P) as assessed by nuclear magnetic resonance (NMR) spectroscopy in patients with type IIa or IIb hyperlipidemia.

Methods and results: This was an analysis of a previously reported 24-week randomized, double-blind study in type IIa/IIb hyperlipidemic patients randomized to treatment with E/S (10/20 mg/day)+N (titrated to 2 g/day) or N (titrated to 2 g/day) or E/S (10/20 mg/day). Samples from a subset of patients (577 of 1220) were available for post hoc analysis of LDL-P and HDL-P by NMR spectroscopy. Increases in HDL-P (+16.2%) and decreases in LDL-P (-47.7%) were significantly greater with E/S+N compared with N (+9.8% for HDL-P and -21.5% for LDL-P) and E/S (+12.8% for HDL-P and -36.8% for LDL-P). In tertile analyses, those with the lowest baseline HDL-P had the greatest percent increase in HDL-P (N, 18.4/7.9/2.1; E/S, 19.3/12.2/5.3; and E/S+N, 26.9/13.8/6.9; all P<0.001). Individuals in the highest tertile of LDL-P had the greatest percent reduction in LDL-P (N, 18.3/23.1/24.6; E/S, 29.7/38.3/41.8; and E/S+N, 44.3/49.0/50.5; all P<0.001).

Conclusions: These results suggest that E/S+N improves lipoprotein particle number, consistent with its lipid-modifying benefits in type IIa or IIb hyperlipidemia patients and may exert the greatest effect in those with high LDL-P and low HDL-P at baseline.

Trial registration: NCT00271817.

Keywords: NMR spectroscopy; ezetimibe; lipoprotein particle number; lipoproteins; niacin; statins.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Azetidines / adverse effects
  • Azetidines / therapeutic use*
  • Biomarkers / blood
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Combinations
  • Drug Therapy, Combination
  • Ezetimibe, Simvastatin Drug Combination
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipidemias / blood
  • Hyperlipidemias / diagnosis
  • Hyperlipidemias / drug therapy*
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Lipoproteins, HDL / blood*
  • Lipoproteins, LDL / blood*
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Niacin / adverse effects
  • Niacin / therapeutic use*
  • Particle Size
  • Simvastatin / adverse effects
  • Simvastatin / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Azetidines
  • Biomarkers
  • Delayed-Action Preparations
  • Drug Combinations
  • Ezetimibe, Simvastatin Drug Combination
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Niacin
  • Simvastatin

Associated data