One-Year Outcomes of Out-of-Hospital Administration of Intravenous Glucose, Insulin, and Potassium (GIK) in Patients With Suspected Acute Coronary Syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial)

Abstract

The IMMEDIATE Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefit. Here we report 1-year outcomes. Pre-specified 1-year endpoints of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality, and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Among 871 participants randomized to GIK vs. placebo, respectively, death occurred within 1 year in 11.6% vs. 13.5% (unadjusted hazard ratio [HR] 0.83; 95% CI 0.57, 1.23, P=0.36). The composite of cardiac arrest or 1-year mortality was 12.8% vs. 17.0% (HR 0.71; 95% CI 0.50, 1.02, P=0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% vs. 17.2% (HR 0.98; 95% CI 0.70, 1.37, P=0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% vs. 20.4% (HR 0.85; 95% CI 0.62, 1.16, P=0.30). Among patients presenting with suspected ST elevation myocardial infarction (STEMI), hazard ratios for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33, 1.27, P=0.21); 0.52 (95% CI 0.30, 0.92, P=0.03); 0.63 (95% CI 0.35, 1.16, P=0.14); and 0.51 (95% CI 0.30, 0.87, P=0.01). Among patients with suspected ACS, serious endpoints generally were lower with GIK than placebo, but the differences were not statistically significant. However, among those with STEMI, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced.

Obesity induced by high fat diet attenuates postinfarct myocardial remodeling and dysfunction in adult B6D2F1 mice

“…Different experimental [47,48] and clinical studies [49][50][51] observed a beneficial effect of glucoseinsulin-potassium (GIK) infusion against myocardial reperfusion injury. In the IMMEDIATE trial, the only clinical trial in which GIK was administered well before reperfusion in all patients, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced in a pre-specified subgroup of patients with ongoing acute myocardial infarction [51]. In addition, insulin but not glucose or potassium has been shown to directly activate PI3K/Akt/eNOS signaling, leading to cardiovascular protection [52].…”

Genetic modifiers of response to glucose–insulin–potassium (GIK) infusion in acute coronary syndromes and associations with clinical outcomes in the IMMEDIATE trial

“…There was no significant difference with treatment in the composite outcome of 1-year death or heart failure or cardiac arrest. 17 …”

Insulin in Acute Coronary Syndrome: a Narrative Review with Contemporary Perspectives

“…However, in 5 studies the rates were not mentioned at all 7 [28,26,27,29,21]. Some studies recorded symptomatic hypoglycaemia only (not biochemical) and this would 8 significantly underestimate true biochemical hypoglycemia [22,25].…”

“…Free fatty acids are normally the primary fuel source for the heart but are toxic to the 17 myocardium in the ischemic setting causing sarcolemmal and mitochondrial membrane disruption [15]. evidence in favour of GIK (total 525 patients) [21,22], seven showed no difference (25,496 patients) [23][24][25][26][27][28][29], and 7 one showed increased harm (954 patients) [30].…”