HONOLULU – In patients who were hyperglycemic following an acute ischemic stroke, intensive insulin control using a continuous insulin drip and an aggressive blood glucose target of 80-130 mg/dL provided no incremental benefit in clinical outcome, compared with a more standard approach of serial, subcutaneous insulin injections and a moderate blood glucose target in a multicenter, U.S. trial with more than 1,100 patients.
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Dr. Karen C. Johnston
The results also highlighted the potential downside to aggressive insulin treatment, with an associated 2.6% incidence of severe hypoglycemia, defined as blood glucose falling below 40 mg/dL, Karen C. Johnston, MD, said at the International Stroke Conference sponsored by the American Heart Association.
“Our data suggest that subcutaneously administered insulin with a target blood glucose level of less than 180 mg/dL is the preferred treatment” because it produces similar efficacy without causing any episodes of severe hypoglycemia, concluded Dr. Johnston, professor and chair of neurology at the University of Virginia in Charlottesville. “There should be no further debate” over the potential superiority of a glucose target substantially below 180 mg/dL, she added in an interview.
Continuing to use a glucose target of less than 180 mg/dL and treating patients with subcutaneous insulin injections every 6 hours to achieve this will mean substantially less resource use and precludes the need for keeping patients in intensive care beds as is needed with an insulin drip, Dr. Johnston noted. A treatment target of less than 180 mg/dL is also consistent with the most recent American Heart Association stroke treatment guidelines, which listed a blood glucose target of 140-180 mg/dL as a class IIa recommendation (Stroke. 2018 March;49[3]:e66-99).
The SHINE (Stroke Hyperglycemia Insulin Network Effort) trial enrolled 1,151 adults diagnosed with an acute ischemic stroke at 63 U.S. centers during 2012-2018, excluding patients with type 1 diabetes. Patients had to enter the study within 12 hours of their last known well time, and with an elevated blood glucose level, above 110 mg/dL in patients with type 2 diabetes or at or above 150 mg/dL in other patients. The median glucose level of enrolled patients was about 188 mg/dL. Enrolled patients averaged 66 years old, and about 80% had type 2 diabetes. The median time from last known well to randomization was just over 7 hours. Almost two-thirds of the patients received thrombolytic treatment, and about 13% underwent thrombectomy.
During up to 72 hours of treatment following enrollment the patients in the standard-treatment arm showed a fairly steady average blood glucose level of 179 mg/dL; patients in the intensive arm showed a steady average of 118 mg/dL.
The study’s primary end point was the percentage of patients with a favorable outcome 90 days after enrollment based on their modified Rankin scale score at that time, with the scores that qualified for this end point varying depending on stroke severity at baseline. The percentage of patients achieving this was 20.5% among the intensive patients and 21.6% among those who received standard insulin treatment, a difference that was not statistically significant.
The findings left open the question of how to better manage acute ischemic stroke patients who present with hyperglycemia.
“Hyperglycemic stroke patients have worse outcomes than stroke patients without hyperglycemia. More aggressively treating the hyperglycemia did not help these patients, We need to figure out what will help them,” Dr. Johnson said.
SOURCE: Johnston KC et al. ISC 2019, Abstract LB1.
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