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Cited by 1,127Lipoproteins and Cardiovascular HealthAcute Ischemic Stroke ManagementDiabetes, Cardiovascular Risks, and Lipoproteins

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

Open access
Kernan, Walter N., Viscoli, Catherine M., Furie, Karen L., Young, Lawrence H., Inzucchi, Silvio E., Gorman, Mark, Guarino, Peter D., Lovejoy, Anne M. +19 more·2016·New England Journal of Medicine
DOI 10.1056/nejmoa1506930PMC PMC4887756
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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.).

Integrity signals

Registry

Crossref · 10.1056/nejmoa1506930

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

17 of 45 cited sources checked · 11 supported · 0 flagged · accuracy not yet measured

  • Findingown data

    In ancillary analyses using updated stroke and MI definitions, the effect of pioglitazone on the primary outcome was similar, with a hazard ratio of 0.73 (95% CI, 0.60 to 0.88).

    “In ancillary analyses, the effect of pioglitazone on the primary outcome was similar when stroke and myocardial infarction were defined according to updated criteria28,29 (hazard ratio, 0.73; 95% CI, 0.60 to 0.88).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [28] source
    • cites [29] source
  • Premisecitation

    The higher vascular risk linked to insulin resistance may be mediated by associated hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, endothelial dysfunction, hypercoagulability, inflammation, and increased platelet reactivity.

    “The presence of insulin resistance increases the risk of vascular disease, possibly because of associated hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, endothelial dysfunction, hypercoagulability, inflammation, and increased platelet reactivity.7–9”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [7] source

      The opening section links insulin resistance to increased cardiovascular mortality and endothelial dysfunction. Figure 1 describes a possible prothrombotic pathway, and the main text associates inflammation with vascular dysfunction. The paper does not support the full proposed list of mediators: it does not identify hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, or increased platelet reactivity as explanations for the higher vascular risk. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [8] source

      The Abstract (page unavailable) associates insulin resistance with vascular disease and describes dyslipidemia and other metabolic abnormalities as part of a proatherogenic milieu. The “Hyperglycemia and hypertension” section (page unavailable) discusses elevated glucose and compensatory hyperinsulinemia, while noting that the relationship with hypertension is less clear. Our copy does not support the full proposed list of mediators, particularly hypercoagulability and increased platelet reactivity. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [9] source
  • Premisecitation

    Insulin sensitivity may be transiently impaired after a stroke.

    “Because insulin sensitivity may be transiently impaired after a stroke,21 the screening blood test was conducted at least 14 days after the index event.”
    Quote in the paperSubstantial claim1 of 1 sources checked
  • Premisecitation

    Insulin resistance raises the risk of vascular disease.

    “The presence of insulin resistance increases the risk of vascular disease, possibly because of associated hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, endothelial dysfunction, hypercoagulability, inflammation, and increased platelet reactivity.7–9”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [7] source
    • cites [8] source
    • cites [9] source
  • Findingown data

    The diabetes finding was unchanged when a glycated hemoglobin cutoff of 6.5% or more was used, with a hazard ratio of 0.49 (95% CI, 0.38 to 0.64).

    “The finding for diabetes was also unchanged when a cutoff for glycated hemoglobin of 6.5% or more was used in local analysis, consistent with the 2010 ADA recommendation30 (hazard ratio, 0.49; 95% CI, 0.38 to 0.64).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
  • Classified as probably not a substantial claim. 27
  • May combine two claims. 21

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    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”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Thiazolidinedione PPAR-γ agonists are among the most potent insulin-sensitizing drugs available.

    “The thiazolidinedione class of peroxisome proliferator–activated receptor γ (PPAR-γ) agonists are among the most potent insulin-sensitizing drugs available.14”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] source

      The Discussion (page not specified) reports that troglitazone increased insulin-mediated peripheral glucose disposal substantially more than metformin in a small group of patients with type II diabetes. It does not establish that thiazolidinediones as a class are among the most potent insulin-sensitizing drugs available or discuss their PPAR-γ mechanism. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Observational research in 2011 and 2012 suggested that pioglitazone may increase the risk of bladder cancer.

    “Observational research conducted in 2011 and 2012 suggested that pioglitazone may increase the risk of bladder cancer.46,47”
    Quote in the paperNot a substantial claim2 of 2 sources checked

  • May combine two claims.

    Interpretationcitation

    The IRIS results agree with a secondary outcome in PROactive, where death, MI, or stroke was significantly lower with pioglitazone, and with trials showing a favorable effect of pioglitazone on subclinical atherosclerosis progression.

    “However, the IRIS results are consistent with findings regarding a secondary outcome in the PROactive trial (i.e., that the rates of death, myocardial infarction, or stroke were significantly lower with pioglitazone than with placebo) and with findings of trials showing a favorable effect of pioglitazone on the progression of subclinical atherosclerosis among patients with and those without”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [32] source
    • cites [33] source
    • cites [34] source

      The Discussion reports a reduction in PROactive’s secondary composite cardiovascular endpoint and describes slower atherosclerosis progression with pioglitazone in trials involving people with and without type 2 diabetes. It does not specify that PROactive’s secondary endpoint comprised death, myocardial infarction, or stroke, so that detail cannot be verified from this paper. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other research suggests that PPAR-γ agonists might prevent certain cancers.

    “Other research suggests that PPAR-γ agonists might prevent certain cancers.50,51”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [50] source
    • cites [51] source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    HOMA-IR was selected because it is easy to perform and closely correlated with more definitive but complex tests.

    “We selected this measurement because it is easy to perform and is closely correlated with more definitive but complex tests.20,52”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [20] source
    • cites [52] source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    A total of 3895 patients were enrolled, and 67% came from US sites.

    “A total of 3895 patients were enrolled, with 67% from sites in the United States (Fig. S1 in the Supplementary Appendix).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    By 2010 ADA criteria, diabetes was present in 116 of 1939 pioglitazone patients (6.0%) and 129 of 1937 placebo patients (6.7%).

    “According to the 2010 criteria of the ADA (which include a glycated hemoglobin level of ≥6.5% as diagnostic of diabetes), diabetes was present in 116 of 1939 patients (6.0%) in the pioglitazone group and in 129 of 1937 (6.7%) in the placebo group (Table S2 in the Supplementary Appendix).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After 1 year, HOMA-IR index and C-reactive protein levels were lower in the pioglitazone group than in the placebo group.

    “After 1 year, the HOMA-IR index and C-reactive protein level were lower in the pioglitazone group than in the placebo group (Table S6 in the Supplementary Appendix).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Patients in the pioglitazone group had more weight gain, edema, shortness of breath, and bone fractures than those in the placebo group.

    “Patients in the pioglitazone group had more weight gain, edema, shortness of breath, and bone fractures than did patients in the placebo group (Table 3, and Table S7 in the Supplementary Appendix).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    During the trial, fasting glucose, fasting triglycerides, and systolic blood pressure were lower in the pioglitazone group, and diastolic blood pressure was lower in years 1 to 4.

    “During the trial, levels of fasting glucose, fasting triglycerides, and systolic blood pressure were also lower in the pioglitazone group, as was diastolic blood pressure in years 1 to 4.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was no significant between-group difference in other monitored adverse events, except that alanine aminotransferase change was more favorable with pioglitazone.

    “There was no significant between-group difference in the incidence of other monitored adverse events, with the exception of a change in the alanine aminotransferase level, which was more favorable with pioglitazone.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the pioglitazone group, 52.2% gained more than 4.5 kg and 11.4% gained more than 13.6 kg; the corresponding placebo percentages were 33.7% and 4.5%.

    “Among the patients in the pioglitazone group, 52.2% gained more than 4.5 kg and 11.4% gained more than 13.6 kg; the corresponding percentages in the placebo group were 33.7% and 4.5%.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Independent committees adjudicated all outcomes and selected safety events while blinded.

    “All outcomes and selected safety events (i.e., bone fracture, macular edema, and cancer) were adjudicated by the members of independent committees in a blinded fashion.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The primary outcome P value was adjusted for interim monitoring, and the five prespecified time-to-event secondary outcome P values were adjusted for multiple testing with the Hochberg procedure and a family-wise error rate of 0.05.

    “The P value for the primary outcome was adjusted for interim monitoring with the use of East software, version 6.3 (Cytel), and the P values for the five prespecified time-to-event secondary outcomes were adjusted for multiple testing with the Hochberg procedure and a family-wise error rate of 0.05.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Adherence to the study drug was lower in the pioglitazone group than in the placebo group; at exit, 60% of pioglitazone patients and 67% of placebo patients were still taking their assigned drug.

    “Patients in the pioglitazone group had lower adherence to the drug regimen than did those in the placebo group (Table S4 in the Supplementary Appendix); at the exit visit, 60% of the patients in the pioglitazone group were still taking pioglitazone and 67% in the placebo group were still taking placebo.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    No outcomes other than those specified were prespecified.

    “No other outcomes were prespecified.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The 19 patients at that site were removed, leaving a final cohort of 3876 patients: 1939 in the pioglitazone group and 1937 in the placebo group.

    “The 19 patients at this site were removed from the study, resulting in a final cohort of 3876 patients (1939 in the pioglitazone group and 1937 in the placebo group).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All patients gave written informed consent.

    “All the patients provided written informed consent.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All analyses followed an intention-to-treat approach.

    “All analyses were performed on an intention-to-treat basis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The local ethics committee at each site approved trial operations.

    “Trial operations were approved by the local ethics committee at each site.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Enrolling 3136 patients would give 90% power to detect a 4-year cumulative stroke or MI rate 20% lower with pioglitazone than placebo, assuming a two-sided type I error of 0.05 and a 27% placebo outcome rate.

    “We determined that enrollment of 3136 patients would provide a power of 90% to detect a 4-year cumulative rate of stroke or myocardial infarction that was 20% lower in the pioglitazone group than in the placebo group, assuming a two-sided type I error of 0.05 and a 27% outcome rate in the placebo group.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Baseline features were similar between the two groups among patients lost to follow-up.

    “Baseline features were similar for patients who were lost to follow-up in the two groups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    Takeda representatives had no role in developing the protocol, conducting the trial, interpreting data, or preparing the manuscript.

    “Representatives of Takeda were provided with a copy of the protocol (available at NEJM.org) and manuscript but had no role in the development of the protocol, the conduct of the trial, the interpretation of the data, or the preparation of the manuscript.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Eligible patients were randomly assigned in a 1:1 ratio to pioglitazone or matching placebo.

    “Eligible patients were randomly assigned in a 1:1 ratio to receive either pioglitazone or matching placebo.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study was conducted and reported in accordance with the protocol.

    “The study was conducted and reported with fidelity to the protocol.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Four interim analyses of the primary outcome assessed efficacy and futility using the O'Brien-Fleming method.

    “Four interim analyses of the primary outcome were conducted for efficacy and futility with the use of the O’Brien–Fleming method.19”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] source

  • May combine two claims.

    Premisecitation

    Insulin resistance is nearly universal in type 2 diabetes and is also found in more than half of patients without diabetes who have had an ischemic stroke or TIA.

    “Insulin resistance is nearly universal in patients with type 2 diabetes but is also present in more than 50% of patients without diabetes who have had an ischemic stroke or a TIA.6”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    An independent data and safety monitoring board appointed by NINDS monitored the trial.

    “The trial was monitored by an independent data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke, which funded the study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Reasons for stopping the study drug were similar between groups, except more pioglitazone patients stopped for edema or weight gain (172 vs 51) or were removed for safety reasons (146 vs 117).

    “The reasons for drug discontinuation were similar in the two groups, except that more patients in the pioglitazone group than in the placebo group stopped because of edema or weight gain (172 patients vs. 51 patients) or were removed for safety reasons (primarily heart failure, repeated fracture, and incidence of or risk factors for bladder cancer) (146 patients vs. 117 patients).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Over a median follow-up of 4.8 years, 227 patients (5.9%) withdrew consent and 99 (2.6%) were lost to follow-up.

    “During a median follow-up of 4.8 years, a total of 227 patients (5.9%) withdrew consent and 99 (2.6%) were lost-to-follow-up (Fig. S1 in the Supplementary Appendix).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    An alleged irregularity in the informed-consent process at one institution led to halting local research activities while data remained blinded.

    “Alleged irregularity in the informed-consent process at one institution resulted in halting of local research activities while the data were still blinded.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Although no significant treatment effect on total or any specific cancer incidence was observed, the study was not powered to address these questions.

    “Although we did not observe a significant effect of treatment on the incidence of total or any specific cancer, our study was not powered to address these questions.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The mechanism of pioglitazone's bone fracture risk is uncertain, and studies have not shown a consistent effect of the drug on bone density.

    “The mechanism is uncertain, and studies have not shown a consistent effect of the drug on bone density.44,45”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [44] source
    • cites [45] source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Weight gain with PPAR-γ agonists such as pioglitazone reflects increased adipose tissue mass and a tendency for fluid accumulation from renal sodium retention.

    “Weight gain with PPAR-γ agonists, such as pioglitazone, reflects an increase in adipose tissue mass and a tendency for fluid accumulation owing to renal sodium retention.41”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Other measured and unmeasured effects may have contributed to pioglitazone's benefit on the primary outcome.

    “However, other measured and unmeasured effects may have contributed to the benefit of the drug with respect to our primary outcome.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sodium retention, if unchecked, can increase the risk of heart failure.

    “Sodium retention, if unchecked, can also increase the risk of heart failure.42”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] source

  • May combine two claims.

    Premisecitation

    Pioglitazone activates PPAR-γ and partially activates PPAR-α.

    “Pioglitazone activates PPAR-γ and also causes partial activation of PPAR-α.35”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] source

  • May combine two claims.

    Interpretationreasoning

    In IRIS, no greater incidence of heart failure was observed with pioglitazone, probably because patients with a history of heart failure were excluded and safety algorithms triggered dose reduction for excessive weight gain or edema.

    “However, in the IRIS trial, we did not observe a greater incidence of heart failure in the pioglitazone group than in the placebo group, which was probably because we excluded patients with a history of heart failure and used safety algorithms that triggered dose reduction for excessive weight gain or edema.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    To address lack of standardization of plasma insulin, all HOMA-IR testing in IRIS was performed in central laboratories.

    “To account for this, all HOMA-IR testing in the IRIS trial was performed in central laboratories.”
    Quote in the paperNot a substantial claim
40 of 40

  • The authors state this as an assumption.

    Data were missing at random for the cognitive function analysis.

    “We used a repeated-measures covariance-pattern model on the assumption that data were missing at random to analyze the effect of treatment on cognitive function”

  • The paper relies on this without support.

    Missing time-to-event data were noninformative censoring.

    “Missing time-to-event data were treated as noninformative censoring.”
2 of 2

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Cites

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Research works printed but not linked: 1

  1. Teng EL, 1987, J Clin Psychiatry, 48, 314

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Authors
Kernan, W. N., Viscoli, C. M., Furie, K. L., Young, L. H., Inzucchi, S. E., Gorman, M., Guarino, P. D., Lovejoy, A. M., Peduzzi, P. N., Conwit, R., Brass, L. M., Schwartz, G. G., Adams, H. P., Berger, L., Carolei, A., Clark, W., Coull, B., Ford, G. A., Kleindorfer, D., O’Leary, J. R., Parsons, M. W., Ringleb, P., Sen, S., Spence, J. D., Tanne, D., Wang, D., & Winder, T. R.
Affiliations
  • Western University (CA)
  • University of Vermont (US)
  • Yale University (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2016-04-07
Volume
374
Issue
14
Pages
1321-1331
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1506930
PMC
PMC4887756
OpenAlex
W2274836352
Semantic Scholar
192abcbc3012aaf42b8606eddd5adedcee96ce93
Cited by
1,127
References
63
Citations by year
2026: 50 · 2025: 64 · 2024: 93 · 2023: 106 · 2022: 80 · 2021: 128 · 2020: 118 · 2019: 113 · 2018: 119 · 2017: 150 · 2016: 87 · 2014: 1
FWCI
140.87
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • PubMed Central (submittedVersion)
  • Scholarship@Western (Western University) (submittedVersion)
  • Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
  • NOVA (University of Newcastle Australia) (submittedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
pioglitazone, ischemic stroke, transient ischemic attack, insulin resistance, HOMA-IR, secondary stroke prevention, myocardial infarction, weight gain
MeSH terms
Pioglitazone, Aged, Brain Ischemia, Ischemic Attack, Transient, Double-Blind Method, Female, Humans, Hypoglycemic Agents

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