Pioglitazone Prevents Stroke in Patients With a Recent Transient Ischemic Attack or Ischemic Stroke

Background: The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone reduced the risk for a composite outcome of stroke or myocardial infarction among nondiabetic patients with insulin resistance and a recent stroke or transient ischemic attack. The current planned secondary analysis uses updated 2013 consensus criteria for ischemic stroke to examine the effect of pioglitazone on stroke outcomes. Methods: Participants were randomly assigned to receive pioglitazone (45 mg/d target dose) or placebo within 180 days of a qualifying ischemic stroke or transient ischemic attack and were followed for a maximum of 5 years. An independent committee, blinded to treatment assignments, adjudicated all potential stroke outcomes. Time to first stroke event was compared by treatment group, overall and by type of event (ischemic or hemorrhagic), using survival analyses and Cox proportional hazards models. Results: Among 3876 IRIS participants (mean age, 63 years; 65% male), 377 stroke events were observed in 319 participants over a median follow-up of 4.8 years. Pioglitazone was associated with a reduced risk for any stroke at 5 years (8.0% in comparison with 10.7% for the placebo group; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60–0.94; log-rank P =0.01). Pioglitazone reduced risk for ischemic strokes (HR, 0.72; 95% CI, 0.57–0.91; P =0.005) but had no effect on risk for hemorrhagic events (HR, 1.00; 95% CI, 0.50–2.00; P =1.00). Conclusions: Pioglitazone was effective for secondary prevention of ischemic stroke in nondiabetic patients with insulin resistance. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00091949.