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

Abstract

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.

• Authors: Ngoc-Anh Le, Ran Jin, Joanne E Tomassini, Andrew M Tershakovec, David R Neff, Peter W F Wilson
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 2 Issue 4 Pg. e000037 (Aug 07 2013) ISSN: 2047-9980 [Electronic] England
• PMID: 23926117 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Aged
• Azetidines (adverse effects, 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, therapeutic use)
• Hyperlipidemias (blood, diagnosis, drug therapy)
• Hypolipidemic Agents (adverse effects, therapeutic use)
• Lipoproteins, HDL (blood)
• Lipoproteins, LDL (blood)
• Magnetic Resonance Spectroscopy
• Male
• Middle Aged
• Niacin (adverse effects, therapeutic use)
• Particle Size
• Simvastatin (adverse effects, therapeutic use)
• Time Factors
• Treatment Outcome