Poststroke pioglitazone reduces risk in prediabetic patients

  • Spence JD & al.
  • JAMA Neurol
  • 7 Feb 2019

  • curated by Susan London
  • Clinical Essentials
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  • After stroke, pioglitazone (Actos) reduces risk for recurrence and/or myocardial infarction (MI) among patients with prediabetes.

Why this matters

Key results

  • 44.3% of the pioglitazone group, 55.7% of the placebo group had good adherence (taking ≥80% of protocol dose).
  • In this subset, pioglitazone reduced risks for:
    • Stroke and/or MI (HR, 0.57; P=.004).
    • Stroke (0.64; P=.04).
    • Acute coronary syndrome (0.47; P=.01).
    • Stroke, MI, and/or hospitalization for heart failure (0.61; P=.008).
    • Progression to diabetes (0.18; P<.001>
  • Other outcomes:
    • Nonsignificant reductions in overall mortality, cancer, hospitalization.
    • Increases in serious bone fractures, weight gain, edema.
  • Pioglitazone had attenuated benefit in intention-to-treat analysis:
    • stroke and/or MI (HR, 0.70; P=.002);
    • stroke (0.72; P=.01);
    • acute coronary syndrome (0.72; P=.052);
    • stroke, MI, and/or hospitalization for heart failure (0.78; P=.02); and
    • progression to diabetes (0.46; P<.001>

Expert comment

  • In an editorial, Leonardo Pantoni, MD, PhD, writes, "Of significance is the fact that this study might have a more direct impact on real-life practice because it does not require direct insulin measurement, opening new horizons and offering new tools to the armamentarium of physicians who are dedicated to cardiovascular prevention and who are currently mostly focused on the use of drugs with antithrombotic effects and statins."

Study design

  • Post hoc analysis of IRIS randomized controlled trial in patients with prior stroke or transient ischemic attack having insulin resistance (but not diabetes).
  • Randomization: pioglitazone vs placebo.
  • 2885 patients with prediabetes by American Diabetes Association criteria (hemoglobin A1c, 5.7%-6.4%; or fasting plasma glucose, 100-125 mg/dL).
  • Main outcome: recurrent stroke or MI over a median of 4.8 years.
  • Funding: National Institute of Neurological Disorders and Stroke.


  • Analyses based on trial subset.
  • Diabetes determined from fasting glucose, patient report.

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