• Harry P Selker, Joni R Beshansky, John L Griffith, Ralph B D'Agostino, Joseph M Massaro, James E Udelson, Eric J Rashba, Robin Ruthazer, Patricia R Sheehan, Patrice Desvigne-Nickens, Yves D Rosenberg, James M Atkins, Assaad J Sayah, Tom P Aufderheide, Charles E Rackley, Lionel H Opie, Costas T Lambrew, Leonard A Cobb, Bruce A Macleod, Joanne S Ingwall, Robert J Zalenski, and Carl S Apstein.
• Center for Cardiovascular Health Services Research, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA. hselker@tuftsmedicalcenter.org
• Am. Heart J. 2012 Mar 1;163(3):315-22.

BackgroundExperimental studies suggest that metabolic myocardial support by intravenous (IV) glucose, insulin, and potassium (GIK) reduces ischemia-induced arrhythmias, cardiac arrest, mortality, progression from unstable angina pectoris to acute myocardial infarction (AMI), and myocardial infarction size. However, trials of hospital administration of IV GIK to patients with ST-elevation myocardial infarction (STEMI) have generally not shown favorable effects possibly because of the GIK intervention taking place many hours after ischemic symptom onset. A trial of GIK used in the very first hours of ischemia has been needed, consistent with the timing of benefit seen in experimental studies.ObjectiveThe IMMEDIATE Trial tested whether, if given very early, GIK could have the impact seen in experimental studies. Accordingly, distinct from prior trials, IMMEDIATE tested the impact of GIK (1) in patients with acute coronary syndromes (ACS), rather than only AMI or STEMI, and (2) administered in prehospital emergency medical service settings, rather than later, in hospitals, after emergency department evaluation.DesignThe IMMEDIATE Trial was an emergency medical service-based randomized placebo-controlled clinical effectiveness trial conducted in 13 cities across the United States that enrolled 911 participants. Eligible were patients 30 years or older for whom a paramedic performed a 12-lead electrocardiogram to evaluate chest pain or other symptoms suggestive of ACS for whom electrocardiograph-based acute cardiac ischemia time-insensitive predictive instrument indicated a ≥75% probability of ACS, and/or the thrombolytic predictive instrument indicated the presence of a STEMI, or if local criteria for STEMI notification of receiving hospitals were met. Prehospital IV GIK or placebo was started immediately. Prespecified were the primary end point of progression of ACS to infarction and, as major secondary end points, the composite of cardiac arrest or in-hospital mortality, 30-day mortality, and the composite of cardiac arrest, 30-day mortality, or hospitalization for heart failure. Analyses were planned on an intent-to-treat basis, on a modified intent-to-treat group who were confirmed in emergency departments to have ACS, and for participants presenting with STEMI.ConclusionThe IMMEDIATE Trial tested whether GIK, when administered as early as possible in the course of ACS by paramedics using acute cardiac ischemia time-insensitive predictive instrument and thrombolytic predictive instrument decision support, would reduce progression to AMI, mortality, cardiac arrest, and heart failure. It also tested whether it would provide clinical and pathophysiologic information on GIK's biological mechanisms.Copyright © 2012 Mosby, Inc. All rights reserved.

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