Intensive use of insulin to regulate hyperglycemia in acute coronary syndrome (ACS) patients did not reduce infarct size, and may have caused harm, a new study found.
The prospective, open-label study was conducted at a large teaching hospital in the Netherlands. Between 2008 and 2012, 294 patients admitted with ACS and a plasma glucose of 140 to 288 mg/dL were randomized to either intensive glucose management (intravenous insulin therapy targeted at plasma glucose levels of 85 to 110 mg/dl) or conventional management (no insulin therapy unless plasma glucose exceeded 288 mg/dl). Patients with insulin-dependent diabetes before admission were excluded from the study. Results were published online Sept. 9 by JAMA Internal Medicine.
Percutaneous coronary intervention (PCI) was performed on 93.6% of the study patients, at a median of about 30 minutes after admission. The primary endpoint of the study was high-sensitivity troponin T about 72 hours after admission, with secondary endpoints the area under the curve of creatine kinase, myocardial band, release and myocardial perfusion scintigraphy at six weeks. The intensive group (whose median glucose was 112 mg/dl) showed an insignificant decrease in infarct size, as measured by all the endpoints, compared to the conventional group. Although severe hypoglycemia was rare, the intensive group did have a higher incidence of death or spontaneous second myocardial infarction (8 patients [5.7%] vs. 1 [0.7%]; P=0.04).
One possible explanation for the lack of effect is the timing of insulin therapy; it was often delayed until after PCI, a median of five hours after symptom onset. It's also possible that elevated plasma glucose was a marker of severity, rather than a causal factor, the authors speculated. They also noted that rapid delivery of PCI could have limited infarct sizes to the point that glucose control didn't provide further benefits. Based on the lack of benefit and possibility of harm observed, “strict, but not too strict, glucose control” seems to be the appropriate strategy, the authors concluded.
They called for additional research to focus on patients with persistently elevated glucose after PCI, as well as the association between intravenous insulin and early second myocardial infarction. An accompanying commentary also suggested a large trial targeting glucose to 140 mg/dl or below, noting that although this study did not show a significant benefit in infarct size, there was a trend favoring intensive glucose management, and other studies show promise with insulin treatment of hyperglycemia in patients with myocardial infarction.