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Glucose-Insulin-Potassium (GIK) in AMI

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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  1. Glucose-Insulin-Potassium (GIK)in AMI

  2. 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.

  3. 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.

  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 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.

  6. 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.

  7. 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.

  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. 2005;293:437-46.

  9. “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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