title: Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia.
abstract: BACKGROUND
  Improving lipids beyond low-density lipoprotein cholesterol (LDL-C) lowering with statin monotherapy may further reduce cardiovascular risk. Niacin has complementary lipid-modifying efficacy to statins and cardiovascular benefit, but is underutilised because of flushing, mediated primarily by prostaglandin D(2) (PGD(2)). Laropiprant (LRPT), a PGD(2) receptor (DP1) antagonist that reduces niacin-induced flushing has been combined with extended-release niacin (ERN) into a fixed-dose tablet.
  
  
  RESULTS
  Dyslipidaemic patients were randomised to ERN/LRPT 1 g (n = 800), ERN 1 g (n = 543) or placebo (n = 270) for 4 weeks. Doses were doubled (2 tablets/day; i.e. 2 g for active treatments) for 20 weeks. ERN/LRPT 2 g produced significant changes vs. placebo in LDL-C (-18.4%), high-density lipoprotein cholesterol (HDL-C; 20.0%), LDL-C:HDL-C (-31.2%), non-HDL-C (-19.8%), triglycerides (TG; -25.8%), apolipoprotein (Apo) B (-18.8%), Apo A-I (6.9%), total cholesterol (TC; -8.5%), TC:HDL-C (-23.1%) and lipoprotein(a) (-20.8%) across weeks 12-24. ERN/LRPT produced significantly less flushing than ERN during initiation (week 1) and maintenance (weeks 2-24) for all prespecified flushing end-points (incidence, intensity and discontinuation because of flushing). Except for flushing, ERN/LRPT had a safety/tolerability profile comparable with ERN.
  
  
  CONCLUSIONS
  Extended-release niacin/LRPT 2 g produced significant, durable improvements in multiple lipid/lipoprotein parameters. The improved tolerability of ERN/LRPT supports a simplified 1 g-->2 g dosing regimen of niacin, a therapy proven to reduce cardiovascular risk.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065, USA. darbie_maccubbin@merck.com
authors.forename: D
authors.initials: D
authors.lastname: Maccubbin
authors.forename: H E
authors.initials: HE
authors.lastname: Bays
authors.forename: A G
authors.initials: AG
authors.lastname: Olsson
authors.forename: V
authors.initials: V
authors.lastname: Elinoff
authors.forename: A
authors.initials: A
authors.lastname: Elis
authors.forename: Y
authors.initials: Y
authors.lastname: Mitchel
authors.forename: W
authors.initials: W
authors.lastname: Sirah
authors.forename: A
authors.initials: A
authors.lastname: Betteridge
authors.forename: R
authors.initials: R
authors.lastname: Reyes
authors.forename: Q
authors.initials: Q
authors.lastname: Yu
authors.forename: O
authors.initials: O
authors.lastname: Kuznetsova
authors.forename: C McCrary
authors.initials: CM
authors.lastname: Sisk
authors.forename: R C
authors.initials: RC
authors.lastname: Pasternak
authors.forename: J F
authors.initials: JF
authors.lastname: Paolini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D000960:Hypolipidemic Agents; D007211:Indoles; C518174:MK-0524; D009525:Niacin