PM03Data from a new systematic review and meta-analysis provides evidence the pioglitazone can help prevent secondary stroke in people with abnormal glucose metabolism. Pioglitazone reduced major vascular events after ischemic stroke in a recent randomized controlled trial. The purpose of this study was to conduct a meta-analysis of randomized controlled trials to evaluate the effect of pioglitazone therapy in reducing the risk of recurrent stroke in stroke patients.

Ischemic stroke and transient ischemic attack (TIA) affect more than 14 million persons worldwide annually. Affected patients are at increased risk for future cardiovascular eventsand prevention of these adverse outcomes is a major goal in their care.

Treatment of insulin resistance represents a potential new preventive strategy that could be added to standard care after ischemic stroke or TIA. Insulin resistance is nearly universal in patients with type 2 diabetes but is also present in more than 50% of patients without diabetes who have had an ischemic stroke or a TIA. The presence of insulin resistance increases the risk of vascular disease, possibly because of associated hypertension, hyperglycemia, hyperinsulinemia, dyslipidemia, endothelial dysfunction, hypercoagulability, inflammation, and increased platelet reactivity. Clinical strategies to improve insulin sensitivity include exercise, diet, weight reduction, and medications. The thiazolidinedione class of peroxisome proliferator–activated receptor γ (PPAR-γ) agonists is among the most potent insulin-sensitizing drugs available. One medication in this class, pioglitazone, may reduce the risk of cardiovascular events, including stroke, in patients with type 2 diabetes, for whom the drug is currently approved as a glucose-lowering agent. The Insulin Resistance Intervention after Stroke (IRIS) trial was designed to test the hypothesis that pioglitazone would reduce the rates of stroke and myocardial infarction after ischemic stroke or TIA in patients without diabetes who have insulin resistance. It is been postulated by some experts that the benefit of pioglitazone in this patient population may reflect that PPAR (peroxisome proliferator-activated receptor) agonists, in addition to their primary effect on glycemic control, also exert potential beneficial effects on inflammation, lipid and protein metabolism, and vascular wall function.

In a study recently published online December 20 in Stroke, Dr. Saver and colleagues searched the major medical databases over a 50-year span for randomized controlled trials that compared pioglitazone with controls and trials that estimated the hazard ratios and 95% confidence intervals for recurrent stroke associated with pioglitazone therapy in stroke patients. Three randomized controlled trials with 4980 participants were identified from this analysis. Use of pioglitazone in stroke patients with insulin resistance, prediabetes, and diabetes mellitus was associated with lower risk of recurrent stroke (hazard ratio 0.68; 95% confidence interval, 0.50–0.92; P=0.01) and future major vascular events (hazard ratio 0.75; 95% confidence interval, 0.64–0.87; P=0.0001). There was no heterogeneity across trials. There was no evidence of an effect on all-cause mortality and heart failure.

The authors of the recently published Stroke article concluded from their analyses that pioglitazone reduces recurrent stroke and major vascular events in ischemic stroke patients with insulin resistance, prediabetes, and diabetes mellitus.

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