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Intensive Treatment of Hyperglycemia Does Not Improve Functional Outcomes in Acute Ischemic Stroke
abstract
This abstract is available on the publisher's site.
Access this abstract nowImportance
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.
Additional Info
Intensive vs Standard Treatment of Hyperglycemia and Functional Outcome in Patients With Acute Ischemic Stroke: The SHINE Randomized Clinical Trial
JAMA 2019 Jul 23;322(4)326-335, KC Johnston, A Bruno, Q Pauls, CE Hall, KM Barrett, W Barsan, A Fansler, K Van de Bruinhorst, S Janis, VL Durkalski-MauldinFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
A bi-directional association between hyperglycemia and stroke has long been known. Diabetes mellitus is a major risk factor for ischemic stroke, and hyperglycemia often occurs in the setting of an acute stroke; however, the link between tight glycemic control and improved neurological outcomes following ischemic stroke has not been demonstrated.1 A systematic review and meta-analysis of 11 randomized controlled trials found no differences in clinical outcomes following acute stroke in patients treated with tight versus loose glucose control.2 It has been speculated that the narrow difference in mean blood glucose achieved between intensive and loose control groups (121 and 132 mg/dL) may have accounted for the lack of differences in clinical outcomes in these trials.1
This large randomized controlled trial has confirmed that intensive glycemic control (target glucose, 80–130 mg/dL) compared with standard treatment using sliding scale insulin (target glucose 80-179 mg/dL) does not improve 90-day functional outcomes following acute ischemic stroke. A major strength of this trial was the large differential in mean glucose achieved between the two groups (118 vs 179 mg/dL). As expected, there were significantly higher rates of severe hypoglycemia in the intensively treated group. Given this increased risk and lack of clinical benefits observed in this landmark study, hyperglycemia in patients with acute ischemic stroke should be managed as per the general non–critically ill population.
References