Intensive blood sugar control has low value in acute stroke

2019 06 14 22 48 3147 Brain General 400

Contrary to expectations and advice in treatment guidelines, intensive lowering and monitoring of blood sugar did not lead to better outcomes for patients with acute ischemic stroke and hyperglycemia in a large randomized trial funded by the U.S. National Institutes of Health (NIH) and reported in the Journal of the American Medical Association.

The trial -- dubbed the Stroke Hyperglycemia Insulin Network Effort (SHINE) -- compared intensive and standard blood glucose control using insulin in 1,151 acute stroke patients and showed good outcomes for 20% in both cohorts, Dr. Karen Johnston, chair of neurology at the University of Virginia, and colleagues reported (JAMA, July 23/30, 2019, Vol. 322:4, pp. 326-335).

Intensive blood sugar lowering has a big downside -- the risk of hypoglycemia -- but the thinking has been that treating hyperglycemia, which is common in stroke patients, would be of benefit. Professional guidelines from the American Heart Association and the American Stroke Association advise getting blood glucose in between the levels of 140 mg/dL and 180 mg/dL and monitoring it closely to avoid hypoglycemia.

The rationale behind this approach is that approximately 40% of acute ischemic stroke patients have hyperglycemia and this "augments the ischemic injury by multiple potential mechanisms, such as endothelial dysfunction, increased oxidative stress, and impaired fibrinolysis," the authors wrote.

The SHINE study assessed the value of blood glucose lowering based on 90-day outcomes for minimal residual neurological deficits, minimal residual limitations in activities of daily living, and Stroke Specific Quality of Life score. Patients were treated to the target level with insulin shots for up to 72 hours after a stroke.

"The absence of a significant clinical benefit in this study was demonstrated even though there was a considerably lower mean blood glucose concentration in the intensive treatment group compared with the standard treatment group (difference of 61 mg/dL [3.4 mmol/L])," Johnston and colleagues wrote. "This differentiation in glucose control was substantially larger than in previous glucose control acute stroke trials."

The researchers used a computerized decision-support tool in a bid to manage the risk for hypoglycemia but nevertheless reported severe cases of this adverse event, all in the intensive group. Hypoglycemia and other adverse events resulted in a higher discontinuation rate for those on intensive versus standard treatment (24.8% versus 9.6%), they reported.

The study provides strong clinical evidence for the lack of benefits of aggressive blood sugar lowering in acute stroke patients, ending "decades of uncertainty," Dr. Walter Koroshetz, director of the NIH's National Institute of Neurological Disorders and Stroke (NINDS), said in a statement.

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