Year: 2016
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS: In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. RESULTS: By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003). CONCLUSIONS: In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).
Source: New England Journal of Medicine
Authors: Walter N. Kernan, Catherine M. Viscoli, Karen L. Furie, Lawrence H. Young, Silvio E. Inzucchi, Mark Gorman, Peter D. Guarino, Anne M. Lovejoy, Peter N. Peduzzi, Robin Conwit, Lawrence M. Brass, Gregory G. Schwartz, Harold P. Adams, Leo Berger, Antonio Carolei, Wayne Clark, Bruce Coull, Gary A. Ford, Dawn Kleindorfer, John R. O’Leary, Mark W. Parsons, Peter Ringleb, Souvik Sen, J. David Spence, David Tanne, David Wang, Toni R. Winder
Institutions: Western University, University of Iowa, University of Arizona, Oregon Health & Science University, Brown University, Yale University, VA Connecticut Healthcare System, University of Vermont, National Institute of Neurological Disorders and Stroke, Denver VA Medical Center, University of Colorado Anschutz, University of Colorado Denver, Hôpital Charles-Le Moyne, University of L'Aquila, University of Oxford, Oxford University Hospitals NHS Trust, University of Cincinnati, John Hunter Hospital, Heidelberg University, University of South Carolina, Tel Aviv University, Sheba Medical Center, OSF Saint Francis Medical Center, Peoria campus of the University of Illinois System
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2274836352