Pierre Fayad, M.D.
Pioglitazone, a drug used for type 2 diabetes, may prevent recurrent stroke and heart attacks in people with insulin resistance but without diabetes.
The results of the Insulin Resistance Intervention after Stroke (IRIS) trial, presented at the International Stroke Conference last month in Los Angeles and published in the New England Journal of Medicine, suggest a potential new method to prevent stroke and heart attack in high-risk patients who have already had one stroke or transient ischemic attack.
Pierre Fayad, M.D., professor in the University of Nebraska Medical Center Department of Neurological Sciences, and medical director, Nebraska Stroke Center, was the local principal investigator at UNMC in this large, international study, which was funded by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS).
“This is really exciting news,” Dr. Fayad said. “This is the first medication that has been shown to decrease the risk of stroke and heart disease in individuals at high risk for diabetes.”
The study was supported by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS).
The IRIS trial is the first study to provide evidence that a drug targeting cell metabolism may prevent secondary strokes and heart attacks even before diabetes develops. Insulin regulates metabolism and keeps blood sugar levels from getting too high, along with many other processes, in the body. Insulin resistance is a condition in which the body produces insulin but does not use it effectively.
“This study represents a novel approach to prevent recurrent vascular events by reversing a specific metabolic abnormality thought to increase the risk for future heart attack or stroke,” said Walter Koroshetz, M.D., director of the NINDS.
“The IRIS trial supports the value of more research to test the vascular benefits of other interventions such as exercise, diet and medications that have similar effects on metabolism as pioglitazone,” said Walter Kernan, M.D. professor of general medicine at Yale University School of Medicine, New Haven, Conn., and lead author of the study. Dr. Kernan was featured in a UNMC Today story when he visited UNMC in 2009.
Close to 4,000 patients from seven countries who had experienced an ischemic stroke or transient ischemic attack within the previous six months were randomized to receive pioglitazone or placebo for up to five years in addition to standard care. The UNMC/Nebraska Medicine study site enrolled a total of 49 patients from Nebraska and Iowa, ranking as the 11th highest enrolling site in the United States.
Ischemic stroke and transient ischemic attacks can occur when a cerebral blood vessel becomes blocked, cutting off the delivery of oxygen and nutrients to brain tissue.
In this study, stroke or heart attack occurred in 9 percent of participants taking pioglitazone and 11.8 percent of patients on placebo, which was a relative decrease of 24 percent. The results suggest that 28 strokes or heart attacks may be prevented for every 1,000 patients who take pioglitazone for up to five years.
Insulin resistance is a hallmark of type 2 diabetes but also occurs in more than 50 percent of people with ischemic stroke who do not have diabetes. People with diabetes are known to have increased risk of stroke.
Previous research suggested that insulin resistance increases risk for stroke, but the IRIS trial was the first to treat it and suggested that the therapy reduced the risk of recurrent stroke and heart attacks. However, pioglitazone is not FDA-approved for the uses studied in the IRIS trial.
In this study, pioglitazone also reduced the risk of diabetes by 52 percent in the study participants.
The study evidenced an additional known side effect of the drug, which is an increased risk of bone fractures. To help doctors and patients choose the best strategy for preventing recurring strokes, future studies will attempt to identify a person’s risk of bone fractures due to pioglitazone. As approved for use in medical practice, the drug also carries additional side effects.
“More research is needed to determine the mechanisms by which pioglitazone decreases risk for stroke and heart attack and increases bone fracture risk, with the hope of developing strategies that maximize benefit and minimize serious side effects in our patients,” said Dr. Kernan.
This work was supported by the NINDS (NS04486).
The NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.