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


CONCLUSIONS
Coadministered ERN/LRPT + SIM produced marked reductions in atherogenic lipoproteins, with the greatest effect on IDL-C, and increases in protective HDL subclasses.
Section of Atherosclerosis, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, 6565 Fannin, MS A601, Houston, TX 77030, USA. cmb@bcm.tmc.edu
Christie
C
Ballantyne
Gilbert
G
Gleim
Nancy
N
Liu
Christine McCrary
CM
Sisk
Amy O
AO
Johnson-Levonas
Yale
Y
Mitchel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage*; D015990:Placebo Effect; D019821:Simvastatin / Q000008:administration & dosage*; D055815:Young Adult
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D007211:Indoles; C518174:MK-0524; D009525:Niacin; D019821:Simvastatin