Pioglitazone Prevents Stroke in Patients with a Recent TIA or Ischemic Stroke: A Planned Secondary Analysis of the IRIS Trial
Background—The Insulin Resistance Intervention after Stroke (IRIS) trial demonstrated that pioglitazone reduced the risk for a composite outcome of stroke or myocardial infarction among non-diabetic patients with insulin resistance and a recent stroke or TIA. 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 randomized to receive pioglitazone (45 mg per day 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% compared to 10.7 for placebo group; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60 to 0.94; log-rank p=0.01). Pioglitazone reduced risk for ischemic strokes (HR, 0.72; 95% CI, 0.57 to 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 non-diabetic patients with insulin resistance.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00091949
- insulin resistance
- stroke, ischemic
- stroke, hemorrhagic
- cerebrovascular disease/stroke
- clinical trial
- Received July 10, 2017.
- Revision received September 22, 2017.
- Accepted October 4, 2017.