Live from the ISC: Standard treatment of hyperglycaemia in acute ischaemic stroke outperforms an intensive approach



Karen Johnston

Intensive glucose control (80–130mg/dL) does not improve 90-day functional outcome and increases the risk of severe hypoglycaemia. This is the conclusion presented by Karen Johnston, professor of neurology at the University of Virginia School of Medicine, Charlottesville, USA, during the International Stroke Conference (ISC; 6–8 February, Honolulu, USA).

Given that hyperglycaemia is common in acute stroke patients and is associated with worse functional outcomes when compared to stroke patients maintaining a normal blood sugar level, Johnston and colleagues set out to assess the efficacy and safety of up to 72 hours of glucose control using continuous intravenous insulin infusion, compared to standard subcutaneous sliding scale insulin.

Although the study’s findings suggested otherwise, Johnston and her team initially hypothesised that intensive glucose control (target range: 80–130 mg/dL) with IV insulin infusion in hyperglycaemic acute ischaemic stroke patients within 12 hours of symptom onset would elicit favourable outcomes, observed through an absolute 7% improvement measured by the modified Rankin Scale (mRS) at 90 days following stroke. In terms of safety, they theorised that such intensive control will be safe, measured by a <4% increase in severe hypoglycaemia (<40mg/dL) compared to the standard control in acute ischaemic stroke patients treated up to 72 hours.

The SHINE study was a multicentre, randomised controlled trial carried out at 63 sites across the USA, inclusive of 1,151 hyperglycaemic patients enrolled within 12 hours of stroke symptom onset, between April 2002 and August 2018. The trial also implemented a blinded outcomes assessment, while the randomisation algorithm prevented serious imbalance by NIHSS score, IV thrombolysis and clinical centre. Johnston reported that the main exclusion criteria deeming patient’s ineligible included those with: type I diabetes, pre-existing confounding conditions, renal dialysis, as well as patients that were unable to follow the protocol.

Johnston noted that the data safety and monitoring board recommended stopping enrolment after the fourth interim analysis as the necessary enrolment had been reached. The primary efficacy outcome—90-day mRS (baseline severity adjusted)—was achieved by 20.5% of patients in the intensive group, and 21.6% of those in the standard group. However, Johnston reported that the adjusted relative risk was 0.97 (95% confidence interval [CI]: 0.87, 1.08), indicating no difference between the two groups.

Regarding the primary safety outcome, severe hypoglycaemia (<40 mg/dL) occurred in 2.6% of the intensive group and did not occur in the standard group. Statistically speaking, the risk difference was 2.58 (95% CI: 1.29, 3.87), indicative of an increased risk of severe hypoglycaemia in the intensive group. Further efficacy outcomes included a favourable NIHSS (0 or 1) score that was achieved by 43.7% and 44.7% of patients in the intensive and standard group, respectively. Furthermore, a favourable Barthel Index (95–100) was reached by 55.2% and 54.7%, while median stroke specific quality of life (SSQOL) scores were 3.8 and 3.7 for patients in the intensive and standard group, respectively.

Concluding the findings, Johnston stressed that the successful and efficient completion of the SHINE trial has enabled questions to be answered regarding the best glucose control for hyperglycaemic patients that have undergone an acute ischaemic stroke. Despite this, she maintained that intensive glucose control (80–130mg/dL) does not improve 90-day functional outcomes and increases the risk of severe hypoglycaemia. Thus, SQ (subcutaneous) insulin with target <180mg/dL remains the preferred approach.

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