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Impact of Glucose-Insulin-Potassium on Mortality and Morbidity in Over 20,000 Patients With Acute Myocardial Infarction: The CREATE-ECLA International Trial - CREATE-ECLA - GIK
Description:
The goal of the trial was to evaluate treatment with a high-dose glucose, insulin, and potassium (GIK) infusion compared with control in patients with acute myocardial infarction (MI).
Hypothesis:
Treatment with GIK would be associated with a reduction in mortality at 30 days compared with control among patients with acute MI.
Study Design
Study Design:
Patients Enrolled: 20,201
Mean Follow Up: 30 days
Mean Patient Age: Mean age 58.6 years
Female: 22
Patient Populations:
ST-segment elevation MI or new left bundle branch block and presentation within 12 hours of symptom onset
Exclusions:
Known contraindication to GIK; anticipated poor compliance with randomized treatment or life expectancy <1 month
Primary Endpoints:
Death at 30 days
Secondary Endpoints:
Cardiac arrest, cardiogenic shock, and reinfarction
Drug/Procedures Used:
Patients were randomized to treatment with GIK infusion for 24 hours (n=10,091) or control (n=10,110). The GIK solution contained 25% glucose, 50 U/l of insulin, and 80 mEq/l of potassium. Patients also received usual therapy for treatment of MI, including aspirin and reperfusion therapy.
The trial was a factorial design, and patients were also randomized to the low molecular weight heparin reviparin or placebo; the reviparin data are reported separately. Enrollment was conducted in Argentina, Pakistan, India, and China.
Concomitant Medications:
Aspirin (97%), thienopyridine (49%), angiotensin-converting enzyme inhibitors (72%), beta-blockers (70%), lipid-lowering therapy (68%), thrombolytic therapy (74%), and primary percutaneous coronary intervention (PCI) (9%)
Principal Findings:
The majority of patients were treated with a reperfusion regimen of thrombolytic therapy (74%). An additional 9% underwent primary PCI. Median time from symptom onset to treatment was 4.6 hours in the GIK group and 4.7 hours in the control group. Treatment with any GIK was given in 98% of the GIK group, with 84.2% receiving the full 24-hour infusion.
There was no difference in the primary endpoint of 30-day mortality (9.7% for control vs. 10.0% for GIK, hazard ratio [HR] 1.03, p=0.45). There was also no difference in the secondary endpoints of 30-day cardiac arrest (1.5% vs. 1.4%, p=0.51), cardiogenic shock (6.3% vs. 6.6%, p=0.38), or reinfarction (2.4% vs. 2.3%, p=0.81). Another endpoint of recurrent ischemia at seven days was lower in the GIK group (6.5% vs. 5.6%, p=0.004), a finding maintained at 30 days.
There was no difference in the primary endpoint analysis by the subgroups evaluated. There was no difference in pulmonary edema (2.1% control vs. 1.9% GIK, p=0.42) or heart failure (17.4% each, p=0.88).
Interpretation:
Among patients with acute MI, treatment with a high-dose GIK infusion was not associated with a difference in mortality compared with control.
Several previous studies have evaluated the use of high-dose or low-dose GIK in acute MI, but the trials were relatively small and were not powered to detect a difference in mortality. While the individual studies were not adequately powered for mortality, a meta-analysis of the trials suggested that high-dose GIK may reduce mortality.
Despite the promising findings of the meta-analysis, the present study of GIK, which was powered with >20,000 patients, found no difference in mortality or reinfarction. The only positive efficacy analysis was the association of GIK with a reduction in recurrent ischemia, although this was not a primary or secondary endpoint.
References:
The CREATE-ECLA Trial Group Investigators. Effect of Glucose-Insulin-Potassium Infusion on Mortality in Patients With Acute ST-Segment Elevation Myocardial Infarction. JAMA. 2005;293:437-446.
Presented by Shamir R. Mehta at the American Heart Association Scientific Sessions, November 2004, New Orleans, LA.
Keywords: Shock, Cardiogenic, Pulmonary Edema, Thrombolytic Therapy, Insulin, Potassium, Heparin, Low-Molecular-Weight, Heart Failure, Bundle-Branch Block, Coronary Disease, Heart Arrest, Glucose
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