Glucose-Insulin-Potassium (GIK) in AMI

1
Glucose-Insulin-Potassium (GIK)in AMI
2
Glucose-insulin-potassium cocktail
Proposed mechanisms of benefit

• Glucose (G)?Energy efficiency of the
  heartbecomes preferred fuel
• Insulin (I)?Circulating FFA level and
  uptaketoxic to ischemic myocardium
• Potassium (K)?Depleted K levels in
  myocyteslowers risk of ventricular arrhythmias

CREATE-ECLA Trial Group Investigators. JAMA.
2005293437-46.
3
GIK Summary of early trials in AMI
Odds ratio (99 CI)
GIK better
Placebo better
P 0.004
0.72 (0.57-0.90)
0
0.5
1
1.5
2
Fath-Ordoubadi F, Beatt KJ. Circulation.
1997961152-6.
4
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
5
DIGAMI 1 CVD mortality after AMI
0.7
0.7
Total cohort
No insulinlow risk
RRR 28
RRR 51
0.6
P 0.011
P 0.004
0.6
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. 19973141512-15.Malmberg
K et al. Eur Heart J. 1996171337-44.
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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

CREATE-ECLA
DIGAMI 2
Malmberg K et al. Eur Heart J. 2005. Van den
Berghe G. Eur Heart J. 2005. CREATE-ECLA Trial
Group Investigators. JAMA. 2005.
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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 only6 hours after randomization
CREATE-ECLA Trial Group Investigators. JAMA.
2005293437-46.
8
CREATE-ECLA Correlation of baseline glucose with
mortality
Control group, n 10,107
Mortalityat 30 days ()
Glucose tertile
CREATE-ECLA Trial Group Investigators. JAMA.
2005293437-46.
9
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.

Califf RM. JAMA. 2005. CREATE-ECLA Trial Group
Investigators. JAMA. 2005. Fath-Ordoubadi F,
Beatt KJ. Circulation. 1997.