Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial

Am Heart J. 2014 Dec;168(6):823-9.e6. doi: 10.1016/j.ahj.2014.07.016. Epub 2014 Jul 28.

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.

Design: 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.

Summary: 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.

Trial registration: ClinicalTrials.gov NCT00091949.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Cognition Disorders / etiology
  • Cognition Disorders / prevention & control
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Insulin Resistance*
  • Ischemic Attack, Transient* / complications
  • Ischemic Attack, Transient* / mortality
  • Ischemic Attack, Transient* / therapy
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Myocardial Infarction / prevention & control
  • Patient Outcome Assessment
  • Pioglitazone
  • Risk Assessment
  • Risk Factors
  • Secondary Prevention / methods*
  • Stroke* / complications
  • Stroke* / mortality
  • Stroke* / therapy
  • Survival Analysis
  • Thiazolidinediones / administration & dosage*

Substances

  • Hypoglycemic Agents
  • Thiazolidinediones
  • Pioglitazone

Associated data

  • EudraCT/2008-005546-23
  • ClinicalTrials.gov/NCT00091949