Infarct Size and Mortality After Glucose-Insulin-Potassium Infusion in Primary Angioplasty for Acute Myocardial Infarction - Infarct Size and Mortality After Glucose-Insulin-Potassium Infusion in Primary Angioplasty for Acute Myocardial Infarction

Description:

The goal of this trial was to compare the effect of treatment with glucose-insulin-potassium (GIK) infusion versus placebo in patients with acute myocardial infarction (AMI) treated with primary angioplasty.

Hypothesis:

Treatment with GIK compared with placebo in patients with AMI will result in a reduction in mortality at 30 days.

Study Design

Study Design:

Patients Enrolled: 940
Mean Follow Up: 30 days
Mean Patient Age: Mean age 60 years
Female: 76

Patient Populations:

AMI within symptom onset within 24 hours

Exclusions:

Pretreatment with thrombolytic therapy; illness associated with restricted life expectancy

Primary Endpoints:

Mortality at 30 days

Secondary Endpoints:

Infarct size as assessed by cumulative enzyme release in the highest quartile, a LVEF <30%

Drug/Procedures Used:

Patients were randomized to GIK infusion (80 mmol potassium in 500 ml glucose 20%, at a rate of 3 ml/kg/h, and short-acting insulin for 8-12 hours; n=476) or placebo (n=464). All patients underwent primary angioplasty.

Principal Findings:

The large majority of patients had thrombolysis in myocardial infarction (TIMI) grade 3 flow following percutaneous coronary intervention (PCI; 96.4% with GIK vs. 93.8% with controls, p=NS). There was no difference in mortality at 30 days in the GIK arm compared with control (4.8% vs. 5.8%, relative risk [RR] 0.82, p=NS). However, in the subgroup of 856 patients (91%) without signs of heart failure (Killip class I), mortality was reduced in the GIK arm (RR 0.28, p=0.01). Cumulative enzyme release in the highest quartile occurred less frequently in the GIK arm versus the control arm (22% vs. 29%, p=0.05).

Left ventricular ejection fraction (LVEF) <30% also occurred less frequently in the GIK arm versus the control arm (12% vs. 18%, p=0.01). The composite of death, MI, or repeat PCI did not differ between the arms (8.0% vs. 9.9%, RR 0.79, p=0.08), but was significantly lower in the GIK arm when restricted to patients with Killip I on admission.

Interpretation:

Among patients with AMI undergoing primary angioplasty, treatment with GIK infusion was associated with a reduction in the frequency of the highest quartile of enzyme release, but was not associated with a difference in 30-day mortality in the total study population. Earlier studies showed a trend toward benefit with GIK infusion, but the studies were small, used varying doses of GIK, and patients were infrequently treated with primary angioplasty.

In the present trial, mortality was reduced in the subgroup of patients with Killip class I at enrollment. However, given the subgroup nature of the analysis, limited conclusions can be drawn. Further studies in patients without signs of heart failure at presentation may be warranted.

Possible explanation for the lack of benefit in patients with Killip class II-IV was the frequency of early death prior to full therapy in these patients, who remained classified in the GIK arm due to the intent-to-treat nature of the analysis. Additionally, volume overload may have influenced the lack of benefit in these heart failure patients.

References:

van der Horst ICC, et al. Glucose-Insulin-Potassium Infusion in Patients Treated With Primary Angioplasty for Acute Myocardial Infarction. J Am Coll Cardiol 2003;42:784–91.

Presented at Late-Breaking Clinical Trials, ACC 2003.

Clinical Topics: Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Acute Heart Failure

Keywords: Risk, Myocardial Infarction, Potassium, Insulin, Short-Acting, Heart Failure, Coronary Disease, Stroke Volume, Angioplasty, Balloon, Coronary, Glucose


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