Glucose insulin potassium gik in ami
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Glucose-Insulin-Potassium (GIK) in AMI. Glucose-insulin-potassium “cocktail”. Proposed mechanisms of benefit. Glucose (G) Energy efficiency of the heart—becomes p referred fuel Insulin (I) Circulating FFA level and uptake — toxic to ischemic myocardium

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Glucose-Insulin-Potassium (GIK) in AMI

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Glucose insulin potassium gik in ami

Glucose-Insulin-Potassium (GIK)in AMI


Glucose insulin potassium cocktail

Glucose-insulin-potassium “cocktail”

Proposed mechanisms of benefit

  • Glucose (G)Energy efficiency of the heart—becomes preferred fuel

  • Insulin (I)Circulating FFA level and uptake—toxic to ischemic myocardium

  • Potassium (K)Depleted K levels in myocytes—lowers risk of ventricular arrhythmias

CREATE-ECLA Trial Group Investigators. JAMA. 2005;293:437-46.


Gik summary of early trials in ami

GIK: Summary of early trials in AMI

Odds ratio (99% CI)

GIK better

Placebo better

0.72 (0.57-0.90)

P = 0.004

0

0.5

1

1.5

2

Fath-Ordoubadi F, Beatt KJ. Circulation. 1997;96:1152-6.


Major trials of gik in ami

Major trials of GIK in AMI

Malmberg K et al. J Am Coll Cardiol. 1995.

Malmberg K et al. Eur Heart J. 2005.

CREATE-ECLA Trial Group Investigators. JAMA. 2005.

*vs usual care


Digami 1 cvd mortality after ami

DIGAMI 1: CVD mortality after AMI

0.7

0.7

Total cohort

No insulin—low risk

RRR = 28%

RRR = 51%

0.6

0.6

P = 0.011

P = 0.004

0.5

0.5

n = 314

0.4

0.4

26%

n = 306

Mortality

n = 133

0.3

0.3

0.2

0.2

n = 139

19%

0.1

0.1

0

0

0

1

2

3

4

5

0

1

2

3

4

5

Years in study

Control

Insulin-glucose infusion

CHF accounted for 66% of all deaths

Malmberg K et al. BMJ. 1997;314:1512-15.Malmberg K et al. Eur Heart J. 1996;17:1337-44.


Digami 2 and create ecla outcomes show need for glucose control

Treatment groups had identical glucose control

Results show long-term benefit in DIGAMI 1 is explained by better glucose control and not by GIK

Not a glucose control trial

Patients randomized irrespective of baseline glucose

Mean glucose increased from baseline in GIK group

DIGAMI 2 and CREATE-ECLA outcomes show need for glucose control

DIGAMI 2

CREATE-ECLA

Malmberg K et al. Eur Heart J. 2005.

Van den Berghe G. Eur Heart J. 2005.

CREATE-ECLA Trial Group Investigators. JAMA. 2005.


Create ecla effect of gik on mortality glucose

CREATE-ECLA: Effect of GIK on mortality, glucose

200

12.0

187

GIK infusion

162

10.0

148

150

Control*

8.0

Mortality, cumulative events(%)

Meanglucose(mg/dL)

100

6.0

4.0

50

2.0

0

0

Baseline(both groups)

GIKgroup

Control*

0

5

10

15

20

25

30

Days

*Usual care only†6 hours after randomization

CREATE-ECLA Trial Group Investigators. JAMA. 2005;293:437-46.


Create ecla correlation of baseline glucose with mortality

CREATE-ECLA: Correlation of baseline glucose with mortality

Control group, n = 10,107

Mortalityat 30 days

(%)

Glucose tertile

CREATE-ECLA Trial Group Investigators. JAMA. 2005;293:437-46.


What create ecla shows about gik

“Regardless of its scientific rationale and the positive results of small studies, this definitive trial, combined with a previous overview that showed only a modest potential benefit, answers the question beyond reasonable doubt: there is no benefit of GIK therapy.”

What CREATE-ECLA shows about GIK

Califf RM. JAMA. 2005.

CREATE-ECLA Trial Group Investigators. JAMA. 2005.

Fath-Ordoubadi F, Beatt KJ. Circulation. 1997.


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