IRIS Trial Shows Decreased Risk of Stroke and MI Among Insulin-Resistant Patients Treated With Pioglitazone
Treatment with pioglitazone – an insulin-sensitizing drug in the thiazolidinedione class – may result in a decreased risk of stroke and myocardial infarction (MI) in patients without diabetes who have insulin resistance plus a recent history of ischemic stroke or transient ischemic attack (TIA), according to results of the IRIS Trial presented Feb. 17 at the International Stroke Conference and simultaneously published in the New England Journal of Medicine.
The multicenter, double-blind trial randomly assigned either pioglitazone (target dose 45 mg) or a placebo to 3,876 patients who had recently had ischemic stroke or TIA. A primary outcome (fatal or non-fatal stroke or MI) occurred in 9 percent of patients who received pioglitazone and in 11.8 percent of patients who received the placebo. In addition, the rate of progression to diabetes was lower in the pioglitazone group than in the placebo group.
However, results also showed that the patients in the pioglitazone group experienced higher rates of weight gain, edema, and shortness of breath and bone fracture. No significant difference was found in the number of patients with heart failure or incidence of cancer between groups.
In an accompanying editorial, Clay F. Semenkovich, MD, calls the results surprising. “Despite having a history of very effective cerebrovascular treatment, patients who were assigned to the pioglitazone group were 24 percent less likely than those in the placebo group to have a stroke or heart attack … at five years.” He explains that it is unclear how pioglitazone decreased these vascular events. Although some risk factors decreased among patients in the pioglitazone group, low-density lipoprotein cholesterol levels increased.
Though the results of the study “may represent a potentially important therapy,” moving forward, Semenkovich cautions against overzealous prescribing of pioglitazone, noting that the patients in the trial met strict criteria. He adds that pioglitazone’s association with increased risks of weight gain, edema and bone fracture should be considered alongside potential benefits when making patient-specific care decisions.
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