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Original Investigation
July 23/30, 2019

Intensive vs Standard Treatment of Hyperglycemia and Functional Outcome in Patients With Acute Ischemic Stroke: The SHINE Randomized Clinical Trial

Author Affiliations
  • 1Department of Neurology, University of Virginia, Charlottesville
  • 2Department of Neurology, Medical College of Georgia, Augusta University, Augusta
  • 3Department of Public Health Sciences, Medical University of South Carolina, Charleston
  • 4Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas
  • 5Department of Neurology, Mayo Clinic Florida, Jacksonville
  • 6Department of Emergency Medicine, University of Michigan, Ann Arbor
  • 7Brain Institute, University of Virginia, Charlottesville
  • 8National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
JAMA. 2019;322(4):326-335. doi:10.1001/jama.2019.9346
Key Points

Question  Does intensive glucose control improve functional outcome in patients with hyperglycemic acute ischemic stroke?

Findings  This randomized clinical trial included 1151 adults who received either intensive treatment of hyperglycemia (target blood glucose concentration of 80-130 mg/dL) or standard treatment of hyperglycemia (target glucose concentration of 80-179 mg/dL). The proportion of patients achieving a favorable outcome based on the 90-day modified Rankin Scale score was 20.5% in the intensive treatment group and 21.6% in the standard treatment group, which was not statistically significant.

Meaning  Intensive compared with standard glucose control did not improve 90-day functional outcomes in patients with acute ischemic stroke and hyperglycemia.

Abstract

Importance  Hyperglycemia during acute ischemic stroke is common and is associated with worse outcomes. The efficacy of intensive treatment of hyperglycemia in this setting remains unknown.

Objectives  To determine the efficacy of intensive treatment of hyperglycemia during acute ischemic stroke.

Design, Setting, and Participants  The Stroke Hyperglycemia Insulin Network Effort (SHINE) randomized clinical trial included adult patients with hyperglycemia (glucose concentration of >110 mg/dL if had diabetes or ≥150 mg/dL if did not have diabetes) and acute ischemic stroke who were enrolled within 12 hours from stroke onset at 63 US sites between April 2012 and August 2018; follow-up ended in November 2018. The trial included 1151 patients who met eligibility criteria.

Interventions  Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (target blood glucose concentration of 80-130 mg/dL [4.4-7.2 mmol/L]; intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (target blood glucose concentration of 80-179 mg/dL [4.4-9.9 mmol/L]; standard treatment group: n = 570) for up to 72 hours.

Main Outcomes and Measures  The primary efficacy outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) that was adjusted for baseline stroke severity.

Results  Among 1151 patients who were randomized (mean age, 66 years [SD, 13.1 years]; 529 [46%] women, 920 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futility based on prespecified interim analysis criteria. During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. A favorable outcome occurred in 119 of 581 patients (20.5%) in the intensive treatment group and in 123 of 570 patients (21.6%) in the standard treatment group (adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08], P = .55; unadjusted risk difference, −0.83% [95% CI, −5.72% to 4.06%]). Treatment was stopped early for hypoglycemia or other adverse events in 65 of 581 patients (11.2%) in the intensive treatment group and in 18 of 570 patients (3.2%) in the standard treatment group. Severe hypoglycemia occurred only among patients in the intensive treatment group (15/581 [2.6%]; risk difference, 2.58% [95% CI, 1.29% to 3.87%]).

Conclusions and Relevance  Among patients with acute ischemic stroke and hyperglycemia, treatment with intensive vs standard glucose control for up to 72 hours did not result in a significant difference in favorable functional outcome at 90 days. These findings do not support using intensive glucose control in this setting.

Trial Registration  ClinicalTrials.gov Identifier: NCT01369069

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