No improvement in 30-day mortality with high-dose Glucose-Insulin-Potassium (GIK) infusion CREATE-ECLA - GIK Trial Presented at: American Heart Association Scientific Sessions 2004 Presented by: Dr. S.R. Mehta

www. Clinical trial results.org GIK Infusion of high-dose GIK (25% glucose, 50 units/L insulin, and 80 mEq/L KCI) for 24 hours at 1.5 mL/kg per hour  n=10,088 Mean onset-to-treatment = 4.6 hr GIK Infusion of high-dose GIK (25% glucose, 50 units/L insulin, and 80 mEq/L KCI) for 24 hours at 1.5 mL/kg per hour  n=10,088 Mean onset-to-treatment = 4.6 hr Primary Endpoint: 30 day mortality Secondary Endpoints: 30 day cardiac arrest, cardiogenic shock, reinfarction, Safety Endpoints: Pulmonary edema, Heart failure, Killip class > 1, Hyperkalemia, Significant phlebitis, Hypoglycemia Primary Endpoint: 30 day mortality Secondary Endpoints: 30 day cardiac arrest, cardiogenic shock, reinfarction, Safety Endpoints: Pulmonary edema, Heart failure, Killip class > 1, Hyperkalemia, Significant phlebitis, Hypoglycemia CREATE-ECLA - GIK Presented at AHA ,195 patients with acute ST-segment-elevation MI presenting within 12 hours of symptom onset 77.8% male, mean age % received PCI, 74% thrombolytic therapy 97% Aspirin, 72% ACE inhibitors, 70% beta-blockers, 68% lipid-lowering therapy Also randomized to reviparin or placebo – results presented separately 20,195 patients with acute ST-segment-elevation MI presenting within 12 hours of symptom onset 77.8% male, mean age % received PCI, 74% thrombolytic therapy 97% Aspirin, 72% ACE inhibitors, 70% beta-blockers, 68% lipid-lowering therapy Also randomized to reviparin or placebo – results presented separately Usual Care  n=10,107 Mean onset-to-treatment = 4.7 hr Usual Care  n=10,107 Mean onset-to-treatment = 4.7 hr

www. Clinical trial results.org CREATE-ECLA – GIK: Primary endpoint No difference in 30-day mortality between the GIK and control groups 30 DAY MORTALITY p = 0.45 Presented at AHA 2004 %

www. Clinical trial results.org CREATE-ECLA –GIK: Secondary endpoint % Presented at AHA 2004 No difference in the secondary endpoints of cardiac arrest, cardiogenic shock or reinfarction between the two groups p=0.51 p=0.38 p=0.81

www. Clinical trial results.org CREATE-ECLA – GIK: Ischemia GIK was associated with a significant reduction in recurrent ischemia at 7 days. The reduction remained significant at 30 days (p=0.036) Recurrent ischemia was neither a primary nor secondary endpoint Recurrent Ischemia at 7 days p = Presented at AHA 2004 %

www. Clinical trial results.org CREATE-ECLA –GIK: Safety endpoints % Presented at AHA 2004 No difference in incidence of pulmonary edema, heart failure or worse Killip class between the two groups p=0.42 p=0.88 p=0.92

www. Clinical trial results.org CREATE-ECLA –GIK: Safety endpoints % Presented at AHA 2004 p=< p=0.0006

www. Clinical trial results.org CREATE-ECLA –GIK: Summary Among acute MI patients presenting within 12 hours of onset of symptoms, treatment with a high-dose glucose-insulin-potassium infusion was not associated with a difference in the primary endpoint of 30-day mortality compared with control. In addition, the two groups showed no difference in the secondary endpoints of cardiac arrest, cardiogenic shock, and reinfarction at 30 days. GIK was associated with a reduction in recurrent ischemia at 7 and 30 days, but an increase in hyperkalemia, phlebitis and hypoglycemia. These findings differ from a previous meta-analysis of 16 smaller studies, which suggested a reduction in mortality with GIK. Among acute MI patients presenting within 12 hours of onset of symptoms, treatment with a high-dose glucose-insulin-potassium infusion was not associated with a difference in the primary endpoint of 30-day mortality compared with control. In addition, the two groups showed no difference in the secondary endpoints of cardiac arrest, cardiogenic shock, and reinfarction at 30 days. GIK was associated with a reduction in recurrent ischemia at 7 and 30 days, but an increase in hyperkalemia, phlebitis and hypoglycemia. These findings differ from a previous meta-analysis of 16 smaller studies, which suggested a reduction in mortality with GIK.