title: Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial.
abstract: BACKGROUND
  Recurrent vascular events remain a major source of morbidity and mortality after stroke or transient ischemic attack (TIA). The IRIS Trial is evaluating an approach to secondary prevention based on the established association between insulin resistance and increased risk for ischemic vascular events. Specifically, IRIS will test the effectiveness of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class, for reducing the risk for stroke and myocardial infarction (MI) among insulin resistant, nondiabetic patients with a recent ischemic stroke or TIA.
  
  
  METHODS
  Eligible patients for IRIS must have had insulin resistance defined by a Homeostasis Model Assessment-Insulin Resistance > 3.0 without meeting criteria for diabetes. Within 6 months of the index stroke or TIA, patients were randomly assigned to pioglitazone (titrated from 15 to 45 mg/d) or matching placebo and followed for up to 5 years. The primary outcome is time to stroke or MI. Secondary outcomes include time to stroke alone, acute coronary syndrome, diabetes, cognitive decline, and all-cause mortality. Enrollment of 3,876 participants from 179 sites in 7 countries was completed in January 2013. Participant follow-up will continue until July 2015.
  
  
  CONCLUSIONS
  The IRIS Trial will determine whether treatment with pioglitazone improves cardiovascular outcomes of nondiabetic, insulin-resistant patients with stroke or TIA. Results are expected in early 2016.
authors.affiliation: Yale University School of Medicine, New Haven, CT. Electronic address: catherine.viscoli@yale.edu.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Viscoli
authors.affiliation: Yale University School of Medicine, New Haven, CT.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Brass
authors.affiliation: University of L'Aquila, L'Aquila, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Carolei
authors.affiliation: National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Robin
authors.initials: R
authors.lastname: Conwit
authors.affiliation: Oxford University, Oxford, United Kingdom.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Ford
authors.affiliation: Alpert Medical School of Brown University, Providence, RI.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Furie
authors.affiliation: University of Vermont School of Medicine, Burlington, VT.
authors.forename: Mark
authors.initials: M
authors.lastname: Gorman
authors.affiliation: Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven, CT; Yale School of Public Health, New Haven, CT.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Guarino
authors.affiliation: Yale University School of Medicine, New Haven, CT.
authors.forename: Silvio E
authors.initials: SE
authors.lastname: Inzucchi
authors.affiliation: Yale University School of Medicine, New Haven, CT.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Lovejoy
authors.affiliation: University of Newcastle, Newcastle, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Parsons
authors.affiliation: Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven, CT; Yale School of Public Health, New Haven, CT.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Peduzzi
authors.affiliation: University of Heidelberg, Heidelberg, Germany.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ringleb
authors.affiliation: VA Medical Center and University of Colorado School of Medicine, Denver, CO.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Schwartz
authors.affiliation: University of Western Ontario, London, Ontario, Canada.
authors.forename: J David
authors.initials: JD
authors.lastname: Spence
authors.affiliation: Tel Aviv University, Tel Aviv, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Tanne
authors.affiliation: Yale University School of Medicine, New Haven, CT.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Young
authors.affiliation: Yale University School of Medicine, New Haven, CT.
authors.forename: Walter N
authors.initials: WN
authors.lastname: Kernan
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007333:Insulin Resistance; D002546:Ischemic Attack, Transient / Q000150:complications / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D063868:Patient Outcome Assessment; D000077205:Pioglitazone; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention / Q000379:methods*; D020521:Stroke / Q000150:complications / Q000401:mortality / Q000628:therapy; D016019:Survival Analysis; D045162:Thiazolidinediones / Q000008:administration & dosage*
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone