ST elevation myocardial infarction glucose control
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-In-Chief: Anne-Marie Anagnostopoulos, M.D.
Overview
There has been a significant decrease in morbidity and mortality associated with acute coronary syndrome over the past few decades. The mortality from acute coronary syndrome that was somewhere between 30-40% in 1960s has significantly reduced to 6-7% in 2010. This marked improvement is primarily due to the advancement in drug developments, coronary care units, and the clinical trials done in the area. Despite these advancements diabetes put an added challenge in these groups of patients and is associated with poor prognosis. Additionally, hyperglycemia with or without documented history of diabetes acts as a predictor for mortality in the patients with acute coronary syndrome. However, there has been a lack of consensus regarding the glucose levels at which the treatment should be initiated, target glucose level, type of treatment (insulin), mode of insulin administration. Thus, large randomized clinical trials addressing these issues are warranted in this area.
Glucose Control in Acute myocardial infarction (AMI)
Problem statement
- Hyperglycemia has multiple adverse cardiovascular effects, especially in the setting of acute coronary syndromes. It has been associated with worse clinical outcomes among patients with STEMI.
- Although admission hyperglycemia (glucose > 140mg/dL) is observed in approximately 50% of STEMI patients at the time of presentation [1], [2], only approximately 20-25% of STEMI patients have a prior diagnosis of diabetes.
- Kosiborod et al in an observational study done on 17,000 patients found that approximately 41% of AMI patients have persistent hyperglycemia (mean glucose > 140mg/dL) and 14% have persistent severe hyperglycemia (glucose >200 mg/dl)[2].
- Elevated glucose and hemoglobin A1c levels are independent predictors of short and long-term cardiovascular outcomes as found in the DIGAMI study.
- One study found that for every 18mg/dL rise in glucose there was a 4% increase in mortality in non-diabetic patients.
Glucose metrics
- Many clinical trials have tried to search the best glucose metrics that can be used as a prognosis predictor in the patients with acute coronary syndrome.
- Admission hyperglycemia - The Cooperative Cardiovascular Project done with 141,680 patients found a linear relationship between admission hyperglycemia and 30 days and 1 year mortality [1]. These findings were reciprocated in other trials and the entire range of acute coronary syndromes [3].
- Fasting hyperglycemia - Fasting hyperglycemia in patients with acute syndrome has been found to be associated with increased mortality [4].
- Persistent hyperglycemia - Persistent or mean hyperglycemia during the course of hospitalization is considered the best prognostic marker of the mortality in patients with acute coronary syndrome. A recent study involving approximately 17,000 patients showed that patients with persistent hyperglycemia throughout the course of their hospitalization have higher mortality compared to those who don't have persistent hyperglycemia [2], only approximately 20-25% of STEMI patients have a prior diagnosis of diabetes.. These results were reciprocated in trials like [Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation–Estudios Cardiologicos Latin America (CREATE-ECLA)][5] and Hyperglycemia: Intensive Insulin Infusion in Infarction (HI-5)][6].
Pathophysiology
Physiologically, acute hyperglycemia can result in endothelial dysfunction, impaired flow-mediated vasodilation, platelet hyperactivity, and impaired microcirculatory function. Possible explanations for these adverse effects include activation of pro-inflammatory transcription factors, increased free radicals and increased plasminogen activator inhibitor-1. Among STEMI patients in particular, elevated glucose is associated with reduced TIMI 3 flow pre-intervention, lower rates of reperfusion, as well as impaired myocardial perfusion after successful intervention. Moreover, patients with hyperglycemia are often relatively insulinopenic; insulin has many cardiovascular benefits independent of glucose lowering including coronary vasodilation, improved endothelial and platelet function, decreased thromboxane AII levels, and anti-inflammatory effects as well.
- In addition to the association of hyperglycemia with adverse outcomes, hypoglycemia has also been associated with poorer clinical outcomes. When glucose data from a large number of patients enrolled in multiple TIMI trials was analyzed retrospectively, a U-shaped relationship was found between the admission glucose level and adverse outcomes among STEMI patients. In patients with hypoglycemia (glucose <81 mg/dL), the death or MI rate was 10.5% compared to 4.2% in patients with euglycemia (glucose 81-99 mg/dL) and 7.2% in those with hyperglycemia (glucose >199 mg/dL)(3 way p-value was significant at <0.001. )
- More recently, as admission hyperglycemia can be “stress induced” in the setting of an MI, fasting glucose levels in both STEMI and non-STEMI was found to be associated with worse in-hospital and 6 month mortality. Investigators used The Global Registry of Acute Coronary Events (GRACE registry) and analyzed 13,000 available fasting glucose levels in patients who presented with a range of acute coronary syndromes.
Supportive research data
- Baseline characteristics of the patients analyzed from the GRACE registry revealed that only 60% of patients with a fasting glucose >126 mg/dL had a prior diagnosis of diabetes. Also, patients with higher fasting glucose levels included women, those with higher Killip class, hypertension, prior stroke or TIA, and peripheral arterial disease. Patients were stratified into 5 different groups according to the fasting glucose level (<100, 100-125, 126-199, 200-299, and >/= 300 mg/dL). Among STEMI patients, in-hospital death increased as glucose level increased (this was also true for NSTEMI and unstable angina as well). At 6 months, increasing fasting glucose was associated with higher risk of post-discharge death among STEMI and NSTEMI patients (however, there was no similar association for unstable angina patients).
- These observations provided the basis for randomized trials evaluating glucose management in the setting of STEMI.
- Initially, the CREATE-ECLA study used a “metabolic cocktail” (glucose, insulin and potassium or GIK) in STEMI patients to not only treat glucose levels but also to stabilize cell membranes using potassium. However, there was no mortality benefit in patients treated with GIK. Also, the DIGAMI-2 trial attempted to establish that chronic insulin based therapy in STEMI patients would result in improved mortality rates. however, the study results did not support that hypothesis. Despite these initial negative studies, the question of how best to manage glucose effectively in STEMI patients, and if it will lead to improved survival, remains unanswered.
- There are currently trials underway that are addressing whether aggressive glucose control with insulin in STEMI patients (particularly anterior STEMI) improves infarct size and cardiovascular outcomes.
ACC / AHA Guidelines (DO NOT EDIT)[7][8]
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Class IIa1. It is reasonable to use an insulin-based regimen to achieve and maintain glucose levels less than 180 mg/dL while avoiding hypoglycemia for patients with STEMI with either a complicated or uncomplicated course. (Level of Evidence: B) |
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Sources
- The 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction [7]
- The 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction [9]
- The 2009 ACC/AHA Focused update on the guidelines for STEMI and PCI[8]
References
- ↑ 1.0 1.1 Kosiborod M, Rathore SS, Inzucchi SE; et al. (2005). "Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes". Circulation. 111 (23): 3078–86. doi:10.1161/CIRCULATIONAHA.104.517839. PMID 15939812. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ 2.0 2.1 2.2 Kosiborod M, Inzucchi SE, Krumholz HM; et al. (2008). "Glucometrics in patients hospitalized with acute myocardial infarction: defining the optimal outcomes-based measure of risk". Circulation. 117 (8): 1018–27. doi:10.1161/CIRCULATIONAHA.107.740498. PMID 18268145. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Wahab NN, Cowden EA, Pearce NJ, Gardner MJ, Merry H, Cox JL (2002). "Is blood glucose an independent predictor of mortality in acute myocardial infarction in the thrombolytic era?". Journal of the American College of Cardiology. 40 (10): 1748–54. PMID 12446057. Retrieved 2012-04-23. Unknown parameter
|month=ignored (help) - ↑ Suleiman M, Hammerman H, Boulos M; et al. (2005). "Fasting glucose is an important independent risk factor for 30-day mortality in patients with acute myocardial infarction: a prospective study". Circulation. 111 (6): 754–60. doi:10.1161/01.CIR.0000155235.48601.2A. PMID 15699267. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Díaz R, Goyal A, Mehta SR; et al. (2007). "Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction". JAMA : the Journal of the American Medical Association. 298 (20): 2399–405. doi:10.1001/jama.298.20.2399. PMID 18042917. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Cheung NW, Wong VW, McLean M (2006). "The Hyperglycemia: Intensive Insulin Infusion in Infarction (HI-5) study: a randomized controlled trial of insulin infusion therapy for myocardial infarction". Diabetes Care. 29 (4): 765–70. PMID 16567812. Retrieved 2012-04-23. Unknown parameter
|month=ignored (help) - ↑ 7.0 7.1 Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK (2004). "ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction)". Circulation. 110 (9): e82–292. PMID 15339869. Unknown parameter
|month=ignored (help) - ↑ 8.0 8.1 [1]
- ↑ Antman EM, Hand M, Armstrong PW; et al. (2008). "2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration With the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing Committee". Circulation. 117 (2): 296–329. doi:10.1161/CIRCULATIONAHA.107.188209. PMID 18071078. Unknown parameter
|month=ignored (help)