{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T23:01:10Z","timestamp":1769641270541,"version":"3.49.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>The insulin sensitizer, pioglitazone, reduces cardiovascular risk in patients after an ischemic stroke or transient ischemic attack but increases bone fracture risk. We conducted a secondary analysis of the IRIS trial (Insulin Resistance Intervention After Stroke) to assess the effect of pretreatment risk for fracture on the net benefits of pioglitazone therapy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>IRIS was a randomized placebo-controlled trial of pioglitazone that enrolled patients with insulin resistance but without diabetes mellitus within 180 days of an ischemic stroke or transient ischemic attack. Participants were recruited at 179 international centers from February 2005 to January 2013 and followed for a median of 4.8 years. Fracture risk models were developed from patient characteristics at entry. Within fracture risk strata, we quantified the effects of pioglitazone compared with placebo by estimating the relative risks and absolute 5-year risk differences for fracture and stroke or myocardial infarction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>The fracture risk model included points for age, race-ethnicity, sex, body mass index, disability, and medications. The relative increment in fracture risk with pioglitazone was similar in the lower (&lt;median point score) and higher (\u2265 median point score) risk strata. However, the absolute risk difference (ARD) for fracture was less in the low-risk group (5.8% in pioglitazone group versus 4.0% in placebo group; ARD, 1.8%; 95% CI, \u22120.7% to 4.4%) compared with high-risk group (18.0% versus 11.6%; ARD, 6.4%; 95% CI, 3.2% to 9.6%). Reductions in risk for stroke or myocardial infarction did not vary by fracture risk (low-risk ARD, \u22123.7%; high-risk ARD, \u22123.5%). In low-risk patients, pioglitazone prevented 2.0 strokes or myocardial infarctions for each fracture caused, compared with 0.5 among those at high risk.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>A simple point score identifying patients at low risk for fracture may assist in selecting patients with a favorable benefit-risk profile for pioglitazone therapy after ischemic stroke or transient ischemic attack.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.118.022745","type":"journal-article","created":{"date-parts":[[2018,12,24]],"date-time":"2018-12-24T19:00:57Z","timestamp":1545678057000},"page":"95-100","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Scoring System to Optimize Pioglitazone Therapy After Stroke Based on Fracture Risk"],"prefix":"10.1161","volume":"50","author":[{"given":"Catherine M.","family":"Viscoli","sequence":"first","affiliation":[{"name":"From the Department of Internal Medicine, General Medicine (C.M.V., W.N.K.), Yale University School of Medicine, New Haven, CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Kent","sequence":"additional","affiliation":[{"name":"Predictive Analytics and Comparative Effectiveness (PACE) Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston MA (D.M.K.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Conwit","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, Bethesda, MD (R.C.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Dearborn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vascular Neurology (J.L.D.), Yale University School of Medicine, New Haven, CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.","family":"Furie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Alpert Medical School of Brown University, Providence, RI (K.L.F.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Gorman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Maine Medical Group, Portland, ME (M.G.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter D.","family":"Guarino","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.D.G.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvio E.","family":"Inzucchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology (S.E.I.), Yale University School of Medicine, New Haven, CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber","family":"Stuart","sequence":"additional","affiliation":[{"name":"University of Connecticut School of Medicine, Farmington, CT (A.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence H.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiology (L.H.Y.), Yale University School of Medicine, New Haven, CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter N.","family":"Kernan","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, General Medicine (C.M.V., W.N.K.), Yale University School of Medicine, New Haven, CT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the IRIS Trial Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506930"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200932030-00002"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000103683.99399.7E"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-3237"},{"key":"e_1_3_3_6_2","unstructured":"National Institute of Neurological Disorders and Stroke-NIH. 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