title: Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcome (AIM-HIGH) trial.
abstract: OBJECTIVE
  In Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial, addition of extended-release niacin (ERN) to simvastatin in participants with established cardiovascular disease, low high-density lipoprotein cholesterol, and high triglycerides had no incremental benefit, despite increases in high-density lipoprotein cholesterol. Preliminary analysis based on incomplete end point adjudication suggested increased ischemic stroke risk among participants randomized to ERN.
  
  
  METHODS
  This final analysis was conducted after complete AIM-HIGH event ascertainment to further explore potential relationship between niacin therapy and ischemic stroke risk.
  
  
  RESULTS
  There was no group difference in trial primary composite end point at a mean 36-month follow-up among 3414 patients (85% men; mean age, 64±9 years) randomized to simvastatin plus ERN (1500-2000 mg/d) versus simvastatin plus matching placebo. In the intention-to-treat analysis, there were 50 fatal or nonfatal ischemic strokes: 18 (1.06%) in placebo arm versus 32 (1.86%) in ERN arm (hazard ratio [HR], 1.78 [95% confidence interval {CI}, 1.00-3.17; P=0.050). Multivariate analysis showed independent associations between ischemic stroke risk and >65 years of age (HR, 3.58; 95% CI, 1.82-7.05; P=0.0002), history of stroke/transient ischemic attack/carotid disease (HR, 2.18; 95% CI, 1.23-3.88; P=0.0079), elevated baseline Lp(a) (HR, 2.80; 95% CI, 1.25-6.27 comparing the middle with the lowest tertile; HR, 2.31; 95% CI, 1.002-5.30 comparing the highest with the lowest tertile; overall P=0.042) but a nonsignificant association with ERN (HR, 1.74; 95% CI, 0.97-3.11; P=0.063).
  
  
  CONCLUSIONS
  Although there were numerically more ischemic strokes with addition of ERN to simvastatin that reached nominal significance, the number was small, and multivariable analysis accounting for known risk factors did not support a significant association between niacin and ischemic stroke risk.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00120289.
authors.affiliation: From the McMaster University, Hamilton, Ontario, Canada (K.K.T.); Duke University and Durham VA Medical Center, Durham, NC (L.B.G.); St. Louis University, St. Louis, MO (B.R.C., S.C.-F.); Axio Research LLC, Seattle, WA (S.G.); Christiana Care Health Services, Newark, DE (W.S.W.); University of Minnesota, Minneapolis, MN (D.C.A.); Case Western Reserve University School of Medicine, Cleveland, OH (C.A.S.); AbbVie, North Chicago, IL (R.J.P.); LHSC University Hospital, London, Ontario, Canada (W.J.K.); and Samuel S. Stratton VA Medical Center, Albany Medical Center and Albany Medical College, Albany, NY (W.E.B.).
authors.forename: Koon K
authors.initials: KK
authors.lastname: Teo
authors.forename: Larry B
authors.initials: LB
authors.lastname: Goldstein
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Chaitman
authors.forename: Shannon
authors.initials: S
authors.lastname: Grant
authors.forename: William S
authors.initials: WS
authors.lastname: Weintraub
authors.forename: David C
authors.initials: DC
authors.lastname: Anderson
authors.forename: Cathy A
authors.initials: CA
authors.lastname: Sila
authors.forename: Salvador
authors.initials: S
authors.lastname: Cruz-Flores
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Padley
authors.forename: William J
authors.initials: WJ
authors.lastname: Kostuk
authors.forename: William E
authors.initials: WE
authors.lastname: Boden
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000517:prevention & control*; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage* / Q000009:adverse effects; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control*; D014280:Triglycerides / Q000097:blood*
chemical_list: D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D014280:Triglycerides; D009525:Niacin; D019821:Simvastatin
keywords: HDL cholesterol; clinical trial; niacin; stroke