title: Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials.
abstract: BACKGROUND
  The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) showed that adding extended-release niacin-laropiprant (ERN-LRPT) to statin provided no incremental cardiovascular benefit vs placebo (PBO). ERN-LRPT was also associated with an excess of serious adverse experiences (AEs), some of which were unexpected (infections and bleeding). These findings led to the withdrawal of ERN-LRPT from all markets.
  
  
  OBJECTIVE
  We examined the safety profile of ERN-LRPT vs the comparators ERN alone and statins in the ERN-LRPT development program to assess whether similar safety signals were observed to those seen in HPS-THRIVE and whether these might be attributed to ERN or LRPT.
  
  
  METHODS
  Postrandomization safety data from 12 clinical studies, 12 to 52 weeks in duration and involving 11,310 patients, were analyzed across 3 treatments: (1) ERN-LRPT; (2) ERN-NSP (ERN, Merck & Co, Inc or Niaspan [NSP], Abbott Laboratories); and (3) statin-PBO (statin or PBO).
  
  
  RESULTS
  The safety profiles of ERN-LRPT and ERN-NSP were similar, except for less flushing with ERN-LRPT. Nonflushing AEs reported more frequently with ERN-LRPT or ERN-NSP than with statin-PBO were mostly nonserious and typical of niacin (nausea, diarrhea, and increased blood glucose). There was no evidence for an increased risk of serious AEs related to diabetes, muscle, infection, or bleeding.
  
  
  CONCLUSIONS
  Pooled data from 11,310 patients revealed that, except for reduced flushing, the safety profile of ERN-LRPT was similar to that of ERN-NSP; LRPT did not appear to adversely affect the side-effect profile of ERN. The inability to replicate the unexpected AE findings in HPS2-THRIVE could be because of the smaller sample size and substantially shorter duration of these studies.
authors.affiliation: Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.
authors.forename: James
authors.initials: J
authors.lastname: McKenney
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA.
authors.forename: Harold
authors.initials: H
authors.lastname: Bays
authors.affiliation: Clinical Research, Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Gleim
authors.affiliation: Clinical Research, Merck & Co, Inc, Kenilworth, NJ, USA. Electronic address: yale_mitchel@merck.com.
authors.forename: Yale
authors.initials: Y
authors.lastname: Mitchel
authors.affiliation: Late Development Statistics, Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Kuznetsova
authors.affiliation: Late Development Statistics, Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Sapre
authors.affiliation: Clinical Research, Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Waheeda
authors.initials: W
authors.lastname: Sirah
authors.affiliation: Clinical Research, Merck & Co, Inc, Kenilworth, NJ, USA.
authors.forename: Darbie
authors.initials: D
authors.lastname: Maccubbin
mesh_terms: D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D009525:Niacin / Q000008:administration & dosage* / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D007211:Indoles; C518174:MK-0524; D009525:Niacin
keywords: Clinical trials; Extended-release niacin; Laropiprant; Pooled analysis; Safety