Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

Ischemic stroke or transient ischemic attack (TIA) patients are at increased risk for future cardiovascular events. Interestingly, the identification of insulin resistance has been discovered as a risk factor for stroke and myocardial infarction. The resistance of insulin as a risk factor raised the possibility that pioglitazone might benefit patients with cerebrovascular disease. Pioglitazone, which is normally used in patients with Diabetes, improves insulin sensitivity; therefore, Pioglitazone could possibly help with the insulin resistance associated with cardiovascular complications.

In this article, the authors focused on a particular study using the treatment of pioglitazone in patients who had a recent ischemic stroke or TIA. It was a multi center, double-blind trial using 3876 randomly assigned patients. The patients were either treated with pioglitazone (target dose of 45 mg daily) or a placebo. There were 1939 patients in the pioglitazone group and 1937 in the placebo group. The patients involved in the study were not diagnosed with Diabetes, but were found to have insulin resistance based on the HOMA-IR, or homeostasis model assessment of insulin resistance, index.

After 1 year, the HOMA-IR index was lower in the pioglitazone group than in the placebo group. The results after 4.8 years of this study are as follows: A primary outcome (stroke or myocardial infarction) had occurred in 9.0% of the pioglitazone group and in 11.8% of the placebo group. Diabetes developed in 3.8% of the pioglitazone group as compared to 7.7% of the placebo group. Also, pioglitazone was associated with a higher frequency of weight gain (52.2%), edema (35.6%), and bone fracture requiring surgery or hospitalization (5.1%).

In conclusion, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received the placebo. Pioglitazone was also associated with a lower risk of diabetes, but with a higher risk of some of the side effects, such as weight gain, edema, and fracture.



Kernan, Walter N., Viscoli, Catherine M., Furie, Karen L., et al. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. 2016.