Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

作者：Walter N. Kernan, Catherine M. Viscoli, Karen L. Furie, Lawrence H. Young, Silvio E. Inzucchi, Mark Gorman, Peter Guarino, Anne M. Lovejoy, Peter N. Peduzzi, ROBIN A. CONWIT, Lawrence M. Brass, Gregory G. Schwartz, Harold P. Adams, Léo Berger, Antonio Carolei, Wayne M. Clark, Bruce M. Coull, Gary A. Ford, Dawn Kleindorfer, John R. O’Leary, Mark W. Parsons, Peter Arthur Ringleb, Souvik Sen, J. David Spence, David Tanné, David Wang, Toni R. Winder · 发表于：New England Journal of Medicine · 年份：2016 · DOI：10.1056/nejmoa1506930 · 被引用次数：1123 · 研究领域：Lipoproteins and Cardiovascular Health、Acute Ischemic Stroke Management、Diabetes, Cardiovascular Risks, and Lipoproteins

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...