title: Effects of extended-release niacin with laropiprant in high-risk patients.
abstract: BACKGROUND
  Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) cholesterol level, but its clinical efficacy and safety are uncertain.
  
  
  METHODS
  After a prerandomization run-in phase to standardize the background statin-based LDL cholesterol-lowering therapy and to establish participants' ability to take extended-release niacin without clinically significant adverse effects, we randomly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily. The primary outcome was the first major vascular event (nonfatal myocardial infarction, death from coronary causes, stroke, or arterial revascularization).
  
  
  RESULTS
  During a median follow-up period of 3.9 years, participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower and an HDL cholesterol level that was an average of 6 mg per deciliter (0.16 mmol per liter) higher than the levels in those assigned to placebo. Assignment to niacin-laropiprant, as compared with assignment to placebo, had no significant effect on the incidence of major vascular events (13.2% and 13.7% of participants with an event, respectively; rate ratio, 0.96; 95% confidence interval [CI], 0.90 to 1.03; P=0.29). Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious (absolute excess as compared with placebo, 3.7 percentage points; P<0.001) and with an increased incidence of diabetes diagnoses (absolute excess, 1.3 percentage points; P<0.001), as well as increases in serious adverse events associated with the gastrointestinal system (absolute excess, 1.0 percentage point; P<0.001), musculoskeletal system (absolute excess, 0.7 percentage points; P<0.001), skin (absolute excess, 0.3 percentage points; P=0.003), and unexpectedly, infection (absolute excess, 1.4 percentage points; P<0.001) and bleeding (absolute excess, 0.7 percentage points; P<0.001).
  
  
  CONCLUSIONS
  Among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.).
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Landray
authors.forename: Richard
authors.initials: R
authors.lastname: Haynes
authors.forename: Jemma C
authors.initials: JC
authors.lastname: Hopewell
authors.forename: Sarah
authors.initials: S
authors.lastname: Parish
authors.forename: Theingi
authors.initials: T
authors.lastname: Aung
authors.forename: Joseph
authors.initials: J
authors.lastname: Tomson
authors.forename: Karl
authors.initials: K
authors.lastname: Wallendszus
authors.forename: Martin
authors.initials: M
authors.lastname: Craig
authors.forename: Lixin
authors.initials: L
authors.lastname: Jiang
authors.forename: Rory
authors.initials: R
authors.lastname: Collins
authors.forename: Jane
authors.initials: J
authors.lastname: Armitage
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000188:drug therapy*; D008078:Cholesterol, LDL / Q000097:blood; D003692:Delayed-Action Preparations; D003920:Diabetes Mellitus / Q000139:chemically induced; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007239:Infections / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000139:chemically induced; D009525:Niacin / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D017211:Treatment Failure
chemical_list: D008078:Cholesterol, LDL; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007211:Indoles; C518174:MK-0524; D009525:Niacin