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

Viscoli, Catherine M.; Brass, Lawrence M.; Carolei, Antonio; Conwit, Robin; Ford, Gary A.; Furie, Karen L.; Gorman, Mark; Guarino, Peter D.; Inzucchi, Silvio E.; Lovejoy, Anne M.; Parsons, Mark W.; Peduzzi, Peter N.; Ringleb, Peter A.; Schwartz, Gregory G.; Spence, J. David; Tanne, David; Young, Lawrence H.; Kernan, Walter N.

doi:10.1016/j.ahj.2014.07.016

Cited by 50Diabetes, Cardiovascular Risks, and LipoproteinsAcute Ischemic Stroke ManagementDiabetes Treatment and Management

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

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Viscoli, Catherine M., Brass, Lawrence M., Carolei, Antonio, Conwit, Robin, Ford, Gary A., Furie, Karen L., Gorman, Mark, Guarino, Peter D. +10 more·2014·American Heart Journal

DOI 10.1016/j.ahj.2014.07.016PMC PMC4254508

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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.

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The trial was international, double-blind, and placebo-controlled.
“The design of this international, double-blind, placebo-controlled clinical trial has been reported previously.17”
From Pioglitazone after Ischemic Stroke or Transient Ischemic Attack (2016) · cites this paper as [17]

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Pioglitazone Prevents Stroke in Patients With a Recent Transient Ischemic Attack or Ischemic Stroke
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Pioglitazone after Ischemic Stroke or Transient Ischemic Attack
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Authors: Viscoli, C. M., Brass, L. M., Carolei, A., Conwit, R., Ford, G. A., Furie, K. L., Gorman, M., Guarino, P. D., Inzucchi, S. E., Lovejoy, A. M., Parsons, M. W., Peduzzi, P. N., Ringleb, P. A., Schwartz, G. G., Spence, J. D., Tanne, D., Young, L. H., & Kernan, W. N.
Affiliations: Yale University (US)
University of L'Aquila (IT)
National Institute of Neurological Disorders and Stroke (US)
University of Oxford (GB)
Brown University (US)
University of Vermont (US)
University of Newcastle Australia (AU)
Heidelberg University (DE)
Denver VA Medical Center (US)
Western University (CA)
Corresponding author: Viscoli, Catherine M.
ORCID: Carolei, Antonio
Conwit, Robin
Ford, Gary A.
Furie, Karen L.
Gorman, Mark
Guarino, Peter D.
Inzucchi, Silvio E.
Parsons, Mark W.
Peduzzi, Peter N.
Ringleb, Peter A.
Schwartz, Gregory G.
Spence, J. David
Young, Lawrence H.
Kernan, Walter N.
Venue: American Heart Journal
Publisher: Elsevier BV
Published: 2014-12
Volume: 168
Issue: 6
Pages: 823-829.e6
ISSN: 0002-8703 (ISSN-L)
DOI: 10.1016/j.ahj.2014.07.016
PMC: PMC4254508
OpenAlex: W2053853324
Cited by: 50
References: 60
Citations by year: 2026: 3 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 9 · 2016: 12 · 2015: 2
FWCI: 6.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: American Heart Journal (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Scholarship@Western (Western University) (submittedVersion)
Funders: National Institute for Health and Care Research (NF-SI-0512-10089)
National Institutes of Health (UL1TR000142, UL1TR000439)
National Institute of Neurological Disorders and Stroke (U01NS044876)
National Center for Advancing Translational Sciences
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: pioglitazone, insulin resistance, ischemic stroke, transient ischemic attack, secondary prevention, thiazolidinediones, IRIS trial, stroke recurrence, myocardial infarction, non-diabetic patients, cardiovascular outcomes, cognitive decline, acute coronary syndrome
MeSH terms: Pioglitazone, Adult, Ischemic Attack, Transient, Cognition Disorders, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Insulin Resistance, Male, Middle Aged, Myocardial Infarction, Risk Factors, Survival Analysis, Risk Assessment, Stroke, Thiazolidinediones, Secondary Prevention, Patient Outcome Assessment

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

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