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


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.
Lipid Research Laboratory, Emory University School of Medicine, Atlanta, GA.
Ngoc-Anh
NA
Le
Ran
R
Jin
Joanne E
JE
Tomassini
Andrew M
AM
Tershakovec
David R
DR
Neff
Peter W F
PW
Wilson
D000368:Aged; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000009:adverse effects / Q000627:therapeutic use*; D010316:Particle Size; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D001384:Azetidines; D015415:Biomarkers; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D009525:Niacin; D019821:Simvastatin
NMR spectroscopy; ezetimibe; lipoprotein particle number; lipoproteins; niacin; statins