Intensive glucose control no better than standard treatment after stroke
Intensive glucose control for up to 72 hours was no better than standard therapy in terms of improving outcomes in hospitalized patients with hyperglycaemia and acute ischaemic stroke in the SHINE* trial, suggesting that intensive glucose control may not be useful in this setting.
The two treatments were equally effective at helping the patients recover from stroke. After 90 days, about 20 percent of the patients showed favourable outcomes regardless of whether they received intensive glucose control or standard treatment. Severe hypoglycaemia (glucose level <40 mg/dL) occurred only in patients receiving intensive glucose control (15 vs 0, for a risk difference of 2.58 percent); p<0. 001). [JAMA 2019;doi:10.1001/jama.2019.9346]
“The extra risks associated with aggressive treatment were not worth it,” said lead investigator Dr Karen Johnston, professor of neurology and associate vice president of clinical and translational research at the University of Virginia in Charlottesville, Virginia, US. “We are grateful to the patients and research teams … who helped us answer this important question. Patients around the world will benefit [from these findings].”
No differences in functional outcomes
During treatment, the mean blood glucose level was 118 mg/dL with intensive glucose treatment vs 179 mg/dL with standard treatment. A favourable outcome occurred in 119 patients (20.5 percent) in the intensive treatment group vs 123 patients (21.6 percent) in the standard treatment group, for an adjusted relative risk (RR) of 0.97 (95 percent confidence interval [CI], 0.87-1.08; p=0.55).
The additional per protocol analysis did not show any significant between-group difference, so did the post hoc analysis of the primary outcome. Similarly, there were no differences in the prespecified secondary 90-day outcomes of minimal residual neurological deficits (NIHSS score), minimal residual limitations in activities of daily living (Barthel Index), and stroke specific quality of life score.
Hypoglycaemia higher with intensive treatment
Treatment was stopped early for hypoglycaemia or other adverse events in 65 patients (11.2 percent) in the intensive treatment group and in 18 patients (3.2 percent) in the standard treatment group. There were no neurological worsening events related to hypoglycaemia. However, the proportion of patients with hypoglycaemia that was reported as a serious adverse event was higher with intensive treatment (3.6 percent vs 0.35 percent with standard treatment).
Death occurred in 54 patients (9.3 percent) in the intensive treatment group and in 65 patients (11.4 percent) in the standard treatment group, for a risk difference of 2.11 percent. Intensive glucose control also necessitated a higher level of care vs standard treatment, with increased supervision from nursing staff.
The study included 1,151 adult patients who developed hyperglycaemia (blood glucose 110 mg/dL with diabetes or 150 mg/dL without diabetes) after an acute ischaemic stroke, and enrolled within 12 hours from stroke onset at 63 US sites. Mean age of the patients was 66 years, 46 percent were women, and 80 percent had diabetes.
Patients were randomized to receive continuous intravenous insulin to a blood glucose target of 80–130 mg/dL (intensive treatment; n=581) or subcutaneous insulin on a sliding scale to a target of 80–179 mg/dL (standard treatment; n=570) for up to 72 hours.
After 90 days, the patients were evaluated for disability, neurologic function, and quality of life. Primary outcome was the proportion of patients with a favourable outcome based on the 90-day modified Rankin Scale score, a global stroke disability scale (0=no symptoms or completely recovered; 6=death), adjusted for baseline stroke severity.
The trial was stopped early when the preplanned interim analysis showed that intensive glucose control did not yield a significant difference in favourable outcomes vs standard treatment.