Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA randomized controlled trial.
BACKGROUND
Glucose-insulin-potassium (GIK) infusion is a widely applicable, low-cost therapy that has been postulated to improve mortality in patients with acute ST-segment elevation myocardial infarction (STEMI). Given the potential global importance of GIK infusion, a large, adequately powered randomized trial is required to determine the effect of GIK on mortality in patients with STEMI.


OBJECTIVE
To determine the effect of high-dose GIK infusion on mortality in patients with STEMI.


METHODS
Randomized controlled trial conducted in 470 centers worldwide among 20,201 patients with STEMI who presented within 12 hours of symptom onset. The mean age of patients was 58.6 years, and evidence-based therapies were commonly used.


METHODS
Patients were randomly assigned to receive GIK intravenous infusion for 24 hours plus usual care (n = 10,091) or to receive usual care alone (controls; n = 10,110).


METHODS
Mortality, cardiac arrest, cardiogenic shock, and reinfarction at 30 days after randomization.


RESULTS
At 30 days, 976 control patients (9.7%) and 1004 GIK infusion patients (10.0%) died (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.95-1.13; P = .45). There were no significant differences in the rates of cardiac arrest (1.5% [151/10 107] in control and 1.4% [139/10,088] in GIK infusion; HR, 0.93; 95% CI, 0.74-1.17; P = .51), cardiogenic shock (6.3% [640/10 107] vs 6.6% [667/10 088]; HR, 1.05; 95% CI, 0.94-1.17; P = .38), or reinfarction (2.4% [246/10,107] vs 2.3% [236/10,088]; HR, 0.98; 95% CI, 0.82-1.17; P = .81). The rates of heart failure at 7 days after randomization were also similar between the groups (16.9% [1711/10,107] vs 17.1% [1721/10,088]; HR, 1.01; 95% CI, 0.95-1.08; P = .72). The lack of benefit of GIK infusion on mortality was consistent in prespecified subgroups, including in those with and without diabetes, in those presenting with and without heart failure, in those presenting early and later after symptom onset, and in those receiving and not receiving reperfusion therapy (thrombolysis or primary percutaneous coronary intervention).


CONCLUSIONS
In this large, international randomized trial, high-dose GIK infusion had a neutral effect on mortality, cardiac arrest, and cardiogenic shock in patients with acute STEMI.
Mehta
Shamir R
SR
Department of Medicine, McMaster University, and Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada. smehta@mcmaster.ca
Yusuf
Salim
S
Díaz
Rafael
R
Zhu
Jun
J
Pais
Prem
P
Xavier
Denis
D
Paolasso
Ernesto
E
Ahmed
Rashid
R
Xie
Changchun
C
Kazmi
Khawar
K
Tai
Javed
J
Orlandini
Andrés
A
Pogue
Janice
J
Liu
Lisheng
L
D000368:Aged; D001786:Blood Glucose; D002314:Cardioplegic Solutions / Q000627:therapeutic use*; D004573:Electrolytes / Q000097:blood; D005260:Female; D005947:Glucose / Q000627:therapeutic use*; D006323:Heart Arrest / Q000453:epidemiology; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D011188:Potassium / Q000097:blood / Q000627:therapeutic use*; D012008:Recurrence; D012770:Shock, Cardiogenic / Q000453:epidemiology
D001786:Blood Glucose; D002314:Cardioplegic Solutions; D004573:Electrolytes; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D005947:Glucose; D011188:Potassium