Effect of Glucose-Insulin-Potassium Infusion on Mortality in Patients With Acute ST-Segment Elevation Myocardial Infarction

Abstract

The CREATE-ECLA Randomized Controlled TrialThe CREATE-ECLA Trial Group Investigators* See also pp 427 and 489.

One‐Year Outcome of Intensive Insulin Therapy Combined to Glucose‐Insulin‐Potassium in Acute Coronary Syndrome: A Randomized Controlled Study

“…In the DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) 1 study6 where GIK administration was associated with aggressive glucose lowering, a significant reduction in 1‐year mortality was demonstrated in patients with ST‐segment elevation myocardial infarction 4. However, 2 other large studies, the DIGAMI 2 trial25 and CREATE‐ECLA‐II (Clinical Trial of Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation‐Estudios Cardiologicos Latinoamerica)12 did not confirm such beneficial effect of GIK therapy in similar patients. The common factor in both negative studies is that glycemic levels were not closely controlled.…”

“…It was suggested that there is probably a link between hyperglycemia and the lack of efficacy of GIK infusion in patients with ACS. Therapy with GIK has long been prescribed during the acute phase of myocardial infarction, but available data on its benefit have been controversial 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14. In the DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) 1 study6 where GIK administration was associated with aggressive glucose lowering, a significant reduction in 1‐year mortality was demonstrated in patients with ST‐segment elevation myocardial infarction 4.…”

“…The potential mechanisms by which GIK could improve clinical outcomes in ACS includes the decrease of the amount of circulating free fatty acids while enhancing the use of glucose as the primary energy substrate for myocardial tissue 3, 4. Although early trials have shown some benefit of GIK treatment,5, 6, 7, 8, 9 other studies have not demonstrated such benefit 2, 10, 11, 12, 13, 14. It was suggested that the inability of GIK to improve outcome might partly be attributable to the tendency of GIK to increase serum glucose levels 15, 16.…”

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

“…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].…”

“…Furthermore, because 6 either median or mean values are consistently quoted this means that a significant percentage of patients 7 received insulin therapy beyond that time frame. For example, in the largest study (CREATE-ECLA) of 20,000 8 patients with ST-elevation myocardial infarction (STEMI), the median time to randomisation was 4.7hrs 9 resulting in 20% of patients receiving GIK 8-12hrs after symptom onset [25]. In the REVIVAL study, 25% of 10 patients received insulin therapy more than 18hrs after symptom onset [24].…”