Intensive vs Standard Treatment of Hyperglycemia and Functional Outcome in Patients With Acute Ischemic Stroke

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 Ն150 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]; 524 [46%] women, 923 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futilitybasedonprespecifiedinterimanalysiscriteria.Duringtreatment,themeanbloodglucoselevel 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.

Management of acute ischemic stroke

“…However, whether tighter control of blood glucose would be beneficial was unclear. The SHINE trial randomized patients to receive either intensive glucose control for 72 hours post-stroke (target 80-130 mg/dL with intravenous insulin infusion) or standard therapy with sliding scale insulin targeted to 80-179 mg/dL 102. The study was stopped for futility at the fourth planned interim analysis after 82% (1151/1400) of the planned maximum number of patients had been enrolled.…”

Stress hyperglycemia is associated with in-hospital mortality in patients with diabetes and acute ischemic stroke

“…The current stroke guidelines recommend that blood glucose be controlled between 140 and 180 mg/dL [32], but the guidelines do not make any distinction between patients with or without diabetes history. The recently completed phase 3 trial Stroke Hyperglycemia Insulin Network Effort (SHINE) demonstrated that intensive blood glucose control (80-130 mg/dL) did not improve the functional outcomes and even increased the risk of severe hypoglycemia [33]. To be worth mentioning, about 80% of the included patients had a history of diabetes.…”

Efficacy and Safety of Insulin Glargine in Patients With Acute Stroke and Hyperglycemia Receiving Intensive Care: Randomized Controlled Study

“…[31] The results of the Stroke Hyperglycemia Insulin Network Effort randomized clinical trial were recently published. [13] The purpose of the trial was to determine and compare the e cacy of intensive and standard treatment of hyperglycemia in patients with acute ischemic stroke. The study comprised 1151 participants randomly assigned to receive continuous intravenous insulin infusion through use of a computerized decision support tool to achieve blood glucose levels of 80 to 130 mg/dL or to receive subcutaneous insulin infusion on a sliding scale to achieve blood glucose levels of 80 to 179 mg/dL for up to 72 h. The results showed that the percentages of patients with favorable functional outcomes were comparable between the intensive and standard treatment groups (20.5% and 21.6%, respectively), but the incidence of early discontinuation of treatment due to hypoglycemia or other adverse effects was higher in the intensive group than in the standard group (11.2% versus 3.2%).…”

“…[12] However, a recent trial suggested that for patients with acute ischemic stroke and hyperglycemia, aggressive intravenous insulin infusion has a signi cantly higher chance of inducing hypoglycemia without absolute clinical bene ts compared with subcutaneous insulin injection. [13] Neutral protamine Hagedorn (NPH) insulin is widely used for the treatment of hyperglycemia during hospitalization. The duration of its effects is approximately 12 h, and it exhibits a peak in its time-action pro le at 5 to 7 h. These properties mean that NPH does not fully mimic the physiological secretion of basal insulin.…”