Expert Review: Acute Coronary Syndrome

Out-of-hospital administration of IV glucose-insulin-potassium in patients with suspected ACS: the IMMEDIATE trial

The authors investigated whether the immediate intravenous (IV) administration of glucose, insulin and potassium (GIK) in the setting of emergency medical services would reduce ischemia-related arrhythmias and myocardial injury in suspected acute coronary syndromes. Compared with placebo, GIK administration was associated with lower rates of the composite outcome of cardiac arrest or in-hospital mortality. 

Background

Experimental investigations suggest that during the very early phase of coronary occlusion, intravenous glucose-insulin-potassium (GIK) reduces ischemia-related arrhythmias and myocardial injury.

Knowledge Gap 

Clinical trials have not consistently shown significant benefits by GIK therapy, possibly due to delayed GIK administration. If immediately administered, GIK may be effective in the clinical settings as well as laboratory settings.

Aim of the Study

To test whether out-of hospital emergency medical service (EMS) administration of GIK in the first hours of suspected acute coronary syndromes (ACS) will reduce progression of ACS to myocardial infarction (MI) and lower mortality.

Methods

The primary endpoint of this study was immediate progression of ACS to MI within 24 hours. The secondary endpoints were mortality at 30 days and a composite of pre-hospital or in-hospital cardiac arrest or in-hospital mortality. The authors performed a randomized, placebo-controlled, double-blind effectiveness trial including 911 (871 enrolled) patients with high probability of ACS. These patients were subjected to intravenous administration of either GIK solution (n = 411) or identical-appearing 5% glucose placebo (n = 460) in the out-of-hospital setting, and continued for 12 hours.

Results

There was no significant difference in the rate of progression to MI among patients who received GIK (48.7%) versus those who received placebo (52.6%) (P = .28). Thirty-day mortality was 4.4% with GIK vs. 6.1% with placebo (P = .27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK vs. 8.7% with placebo (odds ratio, 0.48; 95% CI, 0.27-0.85; P = .01). Among patients with ST-segment elevation (163 with GIK and 194 with placebo), there was no significant difference in progression to MI (85.3% with GIK vs. 88.7% with placebo, P = .34) and in 30-day mortality (4.9% with GIK vs. 7.7% with placebo, P = .29). The composite outcome of cardiac arrest or in-hospital mortality was 6.1% with GIK vs. 14.4% with placebo (odds ratio, 0.39; 95% CI, 0.18-0.82; P = .01). Serious adverse events occurred in 6.8% with GIK vs 8.9% with placebo (P = .26).

Conclusion

EMS administration of intravenous GIK, compared with glucose placebo, was not associated with reduced progression of ACS to MI or improvement in 30-day survival. However, GIK therapy was associated with lower rates of the composite outcome of cardiac arrest or in-hospital mortality.

Perspective-Clinical Impact

In this manuscript of JAMA, Selker and colleges reported the results of the Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care (IMMEDIATE) trial. The concept of GIK therapy to reduce infarct size and mortality by preventing sudden arrhythmias was confirmed by experimental laboratory investigations during 1980’s. In the clinical situation, GIK therapy can be performed simply by paramedics with low cost. While a clinical impact of GIK therapy would be very high, a previous large clinical trial showed no significant benefit of this therapy. Selker et al hypothesized that GIK therapy might be effective if GIK was administered within the first hours of ACS. The present study did not demonstrate significant difference between the placebo and GIK groups in terms of the primary endpoint, progression of ACS to MI. However, favorable results on GIK were observed in the secondary endpoints, the composite outcome of cardiac arrest or in-hospital mortality, which will be clinically more important.

Future studies on patients only within the first hour of symptom onset with total mortality as the primary outcome are needed. In addition, meta-analysis of all previous data examining the effect of GIK on mortality for patients treated within the first hour should be performed to generalize this old but attractive therapy in the clinical situation.

Corresponding author from original paper

Harry P. Selker, MD, MSPH, Institute f or Clinical Research and Health Policy Studies, Tufts Medical Center, 800 Washington St, #63, Boston, MA 02111.  E-mail: hselker@tuftsmedicalcenter.org

Citation: JAMA. 2012 May 9;307(18):1925-33. Epub 2012 Mar 27.

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