Hyperglycemia in ACS. Dr. Imhemed Eljazwi

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1 Hyperglycemia in ACS Dr. Imhemed Eljazwi

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4 Percentage of Population (n = 1181) Prevalence of Hyperglycemia in 181 Cardiac Patients Without Known Diabetes 100% 75% 50% 66% of AMI patients have IGT, or DM (including previously undiagnosed T2DM) - 35% IGT; 31% DM - 25% 0% At Discharge Norhammar A. Lancet. 2002;359:

5 Hyperglycemia In The Hospital Mortality = 16% 11% 26% 63% Diabetes New Hyperglycemia Normal Mortality = 3.0% Mortality = 1.7% Umpierrez, JCEM 87: , 2002

6 Hyperglycemia, in both diabetic and nondiabetic patients, has a significant negative impact on the morbidity and mortality of patients presenting with an acute myocardial infarction (AMI).

7 1mmol/l increase in blood glucose on admission in non-diabetics is associated with : 4% increased risk of death over 50 months (n = 737) 4.3% increased early death (n = 4408) 2% increased risk of death by 90 days (n 11000) Birkhead (MINAP) RCP website 2006 / Stranders et al Arch Intern Med 2004 / Scott et al Diabetes Obes Metab 2007

8 Detrimental Physiological Impact Of Hyperglycemia.

9 Metabolic stress response Stress hormones and peptides Glucose Insulin Immune dysfunction FFA Ketones Lactate Reactive O 2 species Transcription factors Infection dissemination Secondary mediators Cellular injury/apoptosis Inflammation Prolonged Tissue damage hospital stay Disability Acidosis Death Altered tissue/wound repair Thrombosis Infarction/ischemia Clement et al. Diabetes Care 27:553-90, 2004 (i.e., nfkb)

10 Possible mechanisms for glucose toxicity Endothelial dysfunction Promotion of coagulation Glycation of platelet glycoproteins. Amplif. of inflammation. Promotion of apoptosis. Direct myocyte toxicity Prolongation of QT Reduced effectiveness of collaterals.

11 Hyperglycaemia: Predicts incomplete resolution of ST elevation after thrombolysis. is associated with poor flow in infarctrelated artery before primary PCI. is associated with the no-reflow phenomenon after successful primary PCI esp if the glucose level remains elevated ( 180mg/dl ) through the first 24 hrs

12 Hyperglycaemia as an epiphenomenon Plasma catecholamine concentration correlates with infarct size and LVEF. Admission blood glucose asso. with : Larger infarcts.meier et al. Diabetes Care 2005 Faster heart rate. Foo et al. Heart 2003 Heart failure on admission. Kadri et al. Heart 2006 Increased BNP. Bhadriraju et al. Am J Cardiol 2006

13 The Prognostic Role Of Glucose Values in AMI

14 The prevalence of admission hyperglycemia >51% of pt admitted with AMI. Hyperglycemia at the time of admission has been tied to both long and shortterm negative outcomes. Hyperglycemia after hospital admission may yield a more important prognostic role than admission hyperglycemia in terms of morbidity and mortality.

15 Fasting glucose was superior to admission glucose in predicting 30-day mortality in 735 non-diabetic AMI patients. An extensive systemic review showed that persistent glucose levels offer a better model to predict ACS mortality than on-admission glucose level.

16 Hyperglycemia is marker of the stress response. A meta-analysis demonstrated that : with BG ( mg/dl) fold higher risk of death. BG ( mg/dl) ---3-fold higher risk of HF or card. shock. Diabetics with BG ( mg/dl ) had an risk of death (RR1.7).

17 2011 study, a cohort of STEMI patients PCI, in-hospital peak glycemia was an indep. Pred. for early death in patients NOT known diabetes, but not in diabetic. At follow-up, in hospital peak glycemia was able to affect long term survival in both diabetic and non-diabetic patients.

18 The Evidence for Use of Insulin During an Acute Myocardial Infarction

19 RCT S (DIGAMI) Diabetes Insulin-Glucose Infusion in Acute Myocardial infarction (DIGAMI 2) Intense metabolic control by means of insulin in patients with DM and acute myocardial infarction (CREATE-ECLA) Clinical Trial of Reviparin and Metabolic Modulation in MI Treatment Evaluation Estudios Cardiologicos Latin America, (HI-5) The Hyperglycemia Intensive Insulin Infusion In Infarction. (Sweet ACS )

20 Controlling hyperglycemia during AMI admissions has been the target of a great deal of basic and clinical research. The optimal glucose target has been elusive, and contemporary guidelines reflect this.

21 The Diabetes Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) Study 620 DM / AMI patients Conventional Diabetes Care Insulin-Glucose Infusion x 24-h (Target: mg/dl) + Multi-dose insulin injections x 3 mos. Malmberg K et al. BMJ 314: , 1997

22 Results : Mortality was significantly lower in the group assigned to more aggressive insulin therapy at one year. The greatest reduction in mortality was seen in low-risk patients who had not been receiving insulin prior to the infarction.

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24 Limitation : Since DIGAMI also included an outpatient insulin therapy component, the isolated effect of glycemic control in-hospital could therefore not be easily assessed.

25 DIGAMI 2 Group 1 - Intensive* Inpt + Outpt vs. Group 2 - Conventional Inpt + Outpt vs. Group 3 - Intensive Inpt + Conventional opt Methodological flaws (under-recruited; small separation in glucose between groups; lower mortality than expected.) Results: No significant difference in mortality. * Insulin infusion, target BG mg/dl x 24 hrs MDI, target FPG mg/d Malmberg K et al. Europ Heart J 2005

26 CREATE-ECLA : 20,201 pt, on GIK regimen did not demonstrate improved outcomes in AMI. BG > 144 mg/dl had a 2.5-fold higher risk of mortality VS BG < 126 mg/dl. GIK showed in mortality and HF at 30 days post-mi. The overall effect was neutralized by an increase in mortality and HF with this regimen in the immediate 3-day post-mi.

27 HI-5 Trial : Study tested whether an insulin infusion titrated to achieve a target glucose range would be beneficial in acute MI. Hi-5, BG > 140 mg/dll were randomised to intensive insulin therapy (target glucose mg/dl compared with control arm patients

28 There was NO difference between the insulin and control groups IN decrease both mortality and mean 24-hour BG.

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30 Observational evidence observational study of 7820 hyperglycemic patients (admission BG 140 mg/dl ) hospitalized with AMI. Result, lower mean postadmission glucose hospital mortality. There was no difference in mortality rates between insulin-treated and non-insulin treated patients irrespective of mean postadmission glucose level.

31 Conclusions I

32 Hyperglycemia is Risk factor OR Glycemic target?

33 Hyperglycaemia during ACS: Is common May reflect underlying diabetes or excess catecholamine release. Is associated with poorer prognosis, even in the thrombolytic and interventional. May have direct detrimental effects on outcome

34 Conclusions II Treatment of hyperglycaemia: Has not been adequately tested in RCT in ACS. Recent observational analysis suggests treatment that is likely to reduce blood glucose is independently associated with improved early outcome.

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36 Recommendations

37 Acute glucose targets 2009 ACC/AHA gave a weak recommendation for : Insulin based regimen to achieve and maintain BG <180 mg/dl. Hypoglycemia should be avoided..

38 Chronic glycemic control The 2007 ACC/AHA guidelines recommended that : Hemoglobin A1C < 7 % as goal for patients with type 2 diabetes.

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