Cardiovascular researchers at Huntington Medical Research Institutes (HMRI) have reported significant reductions in stroke size and severity using empagliflozin in preclinical models. The findings, presented at the American Heart Association (AHA) Scientific Sessions, suggest a potential new approach to stroke treatment using an existing antidiabetic drug.
Empagliflozin's Impact on Stroke Size
In the study, led by Robert A. Kloner, MD, PhD, and Wangde Dai, MD, empagliflozin (EMPA), a sodium-glucose co-transporter-2 inhibitor, was administered to preclinical stroke models. The results showed that in an acute treatment scenario, intravenous EMPA given ten minutes before middle cerebral artery occlusion and one minute before reperfusion reduced the size of the stroke by 74%. The treatment also reduced brain swelling, a common and dangerous consequence of stroke.
Study Details and Administration
In a chronic treatment group, EMPA was administered for seven days before the experimental stroke model. Researchers observed a significant reduction in the size of cerebral infarctions. The acute treatment involved intravenous administration of EMPA shortly before and during reperfusion.
Mechanism of Action
While the precise mechanism behind empagliflozin's protective effects is still under investigation, researchers hypothesize that it may involve preserving mitochondrial function and reducing reactive oxygen species damage. "We hypothesize that it preserves the function of the mitochondria, the energy factories of the cells, and reduces reactive oxygen species or free radical damage," said Kloner.
The Growing Stroke Epidemic
Stroke incidence is on the rise, with a 70% increase in the absolute number of incident strokes between 1990 and 2019. In the United States alone, approximately 795,000 people experience a new or recurrent stroke each year. Ischemic strokes account for 87% of these cases, while hemorrhagic strokes make up the remaining 13%. The financial burden of stroke on the U.S. healthcare system ranges from $34 to $40 billion annually.
Future Research Directions
HMRI's cardiovascular researchers plan to continue their studies to determine if EMPA is effective after the onset of a stroke and whether it improves long-term neurological function. They speculate that EMPA could potentially be used preventatively in high-risk individuals or acutely to reduce stroke size. "Even with modern approaches to treatment for stroke, death rates remain high and are increasing — and the subsequent disability costs are intolerable," said Kloner. "There is an urgent need for new approaches that will better preserve brain cells in the setting of ischemic stroke and reduce the size of the stroke, also known as cerebral infarction."
