Strict glucose control does not improve outcomes in acute ischemic stroke patients

1. In this randomized controlled trial, intensive hyperglycemia treatment did not lead to improved outcomes compared to standard treatment in patients 90 days after stroke.

2. The intensive therapy group experienced more episodes of hypoglycemia and more adverse events attributed to hypoglycemia.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Hyperglycemia is common in acute ischemic stroke and is associated with worse clinical outcomes, including greater infarct growth and hemorrhagic infarct conversion. However, it is unclear if more intense hyperglycemia management would prevent these sequelae and improve outcomes. In this randomized controlled trial, intensive compared with standard glucose control did not improve 90-day functional outcomes in patients with acute ischemic stroke and hyperglycemia. The intensive therapy group had more episodes of hypoglycemia and more adverse events attributed to hypoglycemia.

This study has several limitations. First, almost half of the patients were enrolled by only six of the clinical sites, and site-specific practices may reduce the generalizability of the results. Second, treatment with intravenous tissue plasminogen activator therapy in 63% of the patients may suggest a selection bias for patients requiring a higher level of care. Third, this trial did not capture recanalization data.

Click to read the study in JAMA (Journal of the American Medical Association)

Relevant Reading: The effect of post-stroke hyperglycaemia on the levels of brain damage and repair-related circulating biomarkers: the Glycaemia in Acute Stroke Study II.

In-Depth [randomized controlled trial]: The Stroke Hyperglycemia Insulin Network Effort (SHINE) included 1151 adults who received either intensive treatment of hyperglycemia (target blood glucose concentration of 80-130mg/dL) or standard treatment of hyperglycemia (target glucose concentration of 80-179mg/dL). Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (standard treatment group: n = 570) for up to 72 hours. The primary efficacy outcome was the proportion of patients with a favorable outcome at 90 days after randomization as defined as a modified Rankin Scale score of 0 in patients with a baseline NIHSS score of 3 to 7, a modified Rankin Scale score of 0 to 1 in patients with a baseline NIHSS score of 8 to 14, and a modified Rankin Scale score of 0 to 2 in patients with a baseline NIHSS score of 15 to 22. Key secondary outcomes included 90-day NIHSS score, 90-day Barthel Index score (scores range from 0-100; higher scores indicate greater ability to perform activities of daily living), and 90-day Stroke Specific Quality of Life score. 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; CI₉₅ 0.87 to 1.08). 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 (2.6%; risk difference 2.58%; CI₉₅ 1.29 to 3.87%).

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