Download VBWG07_HACS5 (9 slides

Glucose-InsulinPotassium (GIK)
in AMI
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
Mortality rate (%)
Study
N
GIK
Odds ratio (99% CI)
Control
GIK better
Heng
27
8.3
0
110
7.3
16.4
134
6.5
12.3
17
0
0
170
11.8
28.2
102
13.9
29.3
200
15.0
16.0
968
21.4
23.6
204
10.6
20.0
1932
16.1
21.0
Placebo better
1977
Stanley
1978
Rogers
1979
Satler
1987
Mittra
1965
Pilcher
1967
Pentecost
1968
MRC
1968
Hjermann
1971
All patients
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
Study
(Year)
N
Treatment*
Outcomes
DIGAMI 1
(1995)
620 DM
IV GIK ≥24 hr + multidose
sc insulin ≥3 months
Mortality
18% In-hospital (NS)
21% 90-days (NS)
29% 1-year (P < 0.05)
DIGAMI 2
(2005)
1253 DM
IV GIK ≥24 hr ± multidose
sc insulin >3 months
Mortality neutral
CREATE-ECLA
(2005)
20,201
IV GIK 24 hr
Mortality, cardiac arrest,
cardiogenic shock,
reinfarction neutral
*vs usual care
Malmberg K et al. J Am Coll Cardiol. 1995.
Malmberg K et al. Eur Heart J. 2005.
CREATE-ECLA Trial Group Investigators. JAMA. 2005.
DIGAMI 1: CVD mortality after AMI
0.7
0.7
Total cohort
RRR = 28%
P = 0.011
0.6
0.5
26%
Mortality
0.5
0.4
n = 306
n = 133
0.3
0.3
0.2
0.2
19%
0.1
RRR = 51%
P = 0.004
0.6
n = 314
0.4
No insulin—low risk
n = 139
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
DIGAMI 2
• Treatment groups had identical
glucose control
• Results show long-term
benefit in DIGAMI 1 is
explained by better glucose
control and not by GIK
CREATE-ECLA
• Not a glucose control trial
• Patients randomized
irrespective of baseline
glucose
• Mean glucose increased from
baseline in GIK group
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
200
12.0
†
162
GIK infusion
10.0
187
150
148
†
Control*
8.0
Mortality,
cumulative
6.0
events
(%)
4.0
Mean
glucose 100
(mg/dL)
50
2.0
0
0
0
5
*Usual care only
†6 hours after randomization
10
15 20
Days
25
30
Baseline GIK Control*
(both group
groups)
CREATE-ECLA Trial Group Investigators. JAMA. 2005;293:437-46.
CREATE-ECLA: Correlation of baseline glucose
with mortality
Control group, n = 10,107
16
14
12
Mortality
at 30 days
(%)
8.5
8
6.6
4
0
Lowest
Middle
Highest
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.”
Califf RM. JAMA. 2005.
CREATE-ECLA Trial Group Investigators. JAMA. 2005.
Fath-Ordoubadi F, Beatt KJ. Circulation. 1997.