title: Atheroprotective lipoprotein effects of a niacin-simvastatin combination compared to low- and high-dose simvastatin monotherapy.
abstract: BACKGROUND
  Niacin has multiple lipoprotein effects that may provide cardiovascular benefit when added to statin monotherapy.
  
  
  METHODS
  In this randomized, placebo-controlled trial (n = 75) of magnetic resonance imaging of carotid atherosclerosis, we performed a secondary comparison of combination niacin-statin (simvastatin 20 mg/Niacin-ER 2G [S20/N]) to monotherapy with moderate (20 mg [S20]) and high-dose (80 mg [S80]) simvastatin on lipids, apolipoproteins (apo), low density lipoprotein (LDL) and high density lipoprotein (HDL) particle subclasses, and inflammatory markers.
  
  
  RESULTS
  At baseline, average age was 71, 72% were male, 62.5% used statins, and average LDL-cholesterol was 111 mg/dL. At 12 months, S20/N, compared to S80, significantly reduced apoB (-36.6% vs -11.9%; P = .05) and lipoprotein(a) (-18% vs +3.5%; P = .001) and had at least an equivalent effect on LDL-cholesterol (-39.3% vs -24.3%; P = .24). The combination reduced the proportion of subjects with atherogenic LDL pattern-B (50% to 11.5%) compared to S80 (56% to 56%) (P = .01). Despite increases in plasma free fatty acids (+62.4%; F = 5.65, P = .005 vs S20 and S80), plasma triglycerides (-29.4%; F = 6.88, P = .002 vs S20 and S80), and very-low-density lipoprotein (-44.2%; F = 7.94, P < .001 vs S20 and S80), levels were reduced by S20/N. S20/N increased HDL-cholesterol levels (+18.1%) as compared to S20 (0%) and S80 (+5.9%) (P < .001 vs both statin arms), largely due to an increase in HDL particle size (+4.6%; P = .01 vs both statin arms).
  
  
  CONCLUSIONS
  We demonstrate that full-dose niacin/moderate-dose simvastatin combination has sustained benefits on atherogenic apoB lipoproteins, at least comparable to high-dose simvastatin, while also raising HDL-cholesterol. Results of large clinical trials will inform whether niacin-statin combinations reduce cardiovascular disease events.
authors.affiliation: The Cardiovascular Institute and the Institute for Translational Medicine and Therapeutics, Philadelphia, PA, USA.
authors.forename: Subha L
authors.initials: SL
authors.lastname: Airan-Javia
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Wolf
authors.forename: Megan L
authors.initials: ML
authors.lastname: Wolfe
authors.forename: Mahlet
authors.initials: M
authors.lastname: Tadesse
authors.forename: Emile
authors.initials: E
authors.lastname: Mohler
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly