@article{94b1688ae2184fd0b73f80590464baf1,
title = "Pioglitazone after ischemic stroke or Transient Ischemic attack",
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.",
author = "Kernan, {W. N.} and Viscoli, {C. M.} and Furie, {K. L.} and Young, {L. H.} and Inzucchi, {S. E.} and M. Gorman and Guarino, {P. D.} and Lovejoy, {A. M.} and Peduzzi, {P. N.} and R. Conwit and Brass, {L. M.} and Schwartz, {G. G.} and Adams, {H. P.} and L. Berger and A. Carolei and W. Clark and B. Coull and Ford, {G. A.} and D. Kleindorfer and O'Leary, {J. R.} and Parsons, {M. W.} and P. Ringleb and S. Sen and Spence, {J. D.} and D. Tanne and D. Wang and Winder, {T. R.}",
note = "Funding Information: Supported by a grant (U01NS044876) from the National Institute of Neurological Disorders and Stroke. Pioglitazone and placebo were provided by Takeda Pharmaceuticals International. Dr. Young reports receiving grant support through his institution from Merck and Mifcor; Dr. Inzucchi, receiving fees for serving on advisory boards from Merck, Janssen, Sanofi, Poxel, Boehringer Ingelheim, Eli Lilly, and AstraZeneca, fees for serving on a data monitoring committee from Novo Nordisk and Intarcia, and fees for serving on a steering committee from Lexicon, serving as an expert witness on behalf of Takeda in a patent litigation deposition, and participating in projects for which funding for continuing medical education has been provided to Yale University by Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Abbott, Merck, and Sanofi; Dr. Peduzzi, receiving consulting fees from Millennium; Dr. Schwartz, receiving grant support from Cerenis, Roche, Resverlogix, Sanofi, and the Medicines Company; Dr. Ford, receiving fees for serving on a trial steering committee from Lundbeck, fees for serving on a data safety monitoring board from Cerevast, fees for serving on advisory boards from Pfizer, Athersys, and Daiichi Sankyo, consulting fees from Pfizer, and lecture fees and travel support from AstraZeneca and Boehringer Ingelheim; Dr. Ringleb, receiving fees for serving on advisory boards from Boehringer Ingelheim, Covidien, Bayer, and Daiichi Sankyo and lecture fees and travel support from Boehringer Ingelheim, Bayer, and Daiichi Sankyo; Dr. Spence, receiving consulting and lecture fees from Bayer and Bristol-Myers Squibb, serving as an officer of and having an equity interest in Vascularis, and performing contract research for Bayer, Bristol-Myers Squibb, Pfizer, Acasti Pharma, POM Wonderful, CVRx, AGA Medical, and W.L. Gore. No other potential conflict of interest relevant to this article was reported. Publisher Copyright: Copyright {\textcopyright} 2016 Massachusetts Medical Society.",
year = "2016",
month = apr,
day = "7",
doi = "10.1056/NEJMoa1506930",
language = "English (US)",
volume = "374",
pages = "1321--1331",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "14",
}