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Intensive insulin added no benefit for hyperglycemia after ischemic stroke

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SHINE results give a clear answer

SHINE was a well-designed trial that was run with a high degree of rigor, and its results advance the field. The results left no doubt that the result was neutral, that intensive insulin management of hyperglycemia immediately after an acute ischemic stroke produced no improvement in 90-day clinical outcomes, compared with standard insulin management, while resulting in an excess of severe hypoglycemia episodes.

Dr. Patrick D. Lyden, professor of neurology, Cedars-Sinai Medical Center, Los Angeles

Dr. Patrick D. Lyden

This study is highly relevant to current practice. Clinicians who manage acute ischemic stroke patients have long been uncertain over the best way to manage hyperglycemia. This topic has a significant back story, with results from several prior studies failing to definitively address the issue. SHINE has now given us a clear message and appears to preclude the need for additional studies of this specific question.

Using a less intensive insulin regimen that does not require a continuous drip is easier. The question of how aggressive treatment needs to be when managing glucose in acute ischemic stroke patients is something that U.S. clinicians who care for stroke patients argue about virtually daily. At my center, Cedars-Sinai in Los Angeles, we have recently used an approach that blended standard insulin treatment with more aggressive treatment. The SHINE results may not be practice changing, but they will be argument changing. The new results will make a difference. We will now stop arguing. We now know what we need to do.

Patrick D. Lyden, MD , is professor and chair of neurology at Cedars-Sinai Medical Center in Los Angeles. He had no relevant disclosures. He made these comments in an interview.



– 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.

Dr. Karen C. Johnston, professor of neurology, University of Virginia, Charlottesville Mitchel L. Zoler/MDedge News

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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