STRATEGIES TO PREVENTION OF MYOCARDIAL INFARCTION IN DIABETES MELLITUS

Diabetic patient with acute myocardial infarction (AMI) have a poorer prognosis. There is increase in mortality rate of diabetic patients with CHD (Atherosclerotic Coronary Heart Disease) Patient with diabetes who survive myocardial infarction have a 40% higher risk of death after 6 years.

Accelerated atherosclerosis in subjects with diabetes long lasting hyper glycemia, subsequent hyperinsulinemia leads to development microvascular disease, endothelial disfunction. Increased transmigration of macrophases and other inflammatory cells into the subendothelium. Macrophages ingest modified LDL cholesterol molecules giving hire to foam cells, the hallmark of atherosclerosis.

Prethrombotic state in subjects with diabetes because platelet have increased number of glycoprotein (GP) IIb/IIIa receptor and aggregate more readily also increased levels of plama fibrinogen and factors VII correlate with increased risk of myocardial infarction and sudden death.

Modifiable risk factor in patient of diabetes

1. Glycemic control: The benefit of good glycemic control in patient with type I and II diabetes for prevention of microvascular disease. The goal of glycemic therapy is to achieve a fasting glucose level between 90-130mg/dl and an A_1c <7% postprandial hyperglycemia is an independent risk factor for CHD.ADA recommended 2 hour post prandial glucose level <180mg/dl.
2. Weight reduction: Type II DM patient are overweight (BMI 25-29.9kg/m²) or obese (BMI ³ 30kg/m²). Excess body fat raises insulin resistance and accelerates a decline in insulin secretion. Weight reduction can reduce insulin resistance. The goal should be to lose 10% of initial body weight gradually over 12 months.
3. Physical activity: Physical inactivity contributes to development of obesity. Physical activity can improve insulin sensitivity lower total cholesterol, LDL cholesterol and TG raises HDL cholesterol and decrease the risk for CHD by improving overall cardiovascular fitness and function. The recommended prescription is ~30min of moderate intensity exercise daily.
4. Lipid Control: Patient with diabetes main an LDL cholesterol of <100mg/dl with an optional goal of <70mg/dl. For patient with TG>200mg/dl, the target goal is a non HDL cholesterol level (total cholesterol – HDL cholesterol) of ≤ 130mg/dl. Also maintain in HDL cholesterol level >40mg/dl for men and >50mg/dl for women. 
5. PROVE IT Trial: A significance reduction in events from using high dose atorvastatin (80mg) in patient with diabetes which achieves mean LDL cholesterol of 62mg/dl compared with standard dose pravastatin (40mg) which achieved mean LDL cholesterol of 95mg/dl. LDL cholesterol level of simvastatin (40mg/day) treated group was 77mg/dl. It is reasonable to prescribe statin therapy for high risk patients, such as those with diabetes even when the LDL cholesterol level in between 70-100mg/dl.
6. Blood Pressure Control: The risk of cardiovascular events and diabetes associated death increases with increase in BP. Even modest BP reduction in diabetic patient (10mmHg systolic and 5mm Hg diastolic) can reduce the risk of developing congestive heart failure.

MICRO-HOPE: Microalbuminuria, cardiovascular, renal outcomes HOPE. Ramipril reduces the incidence of myocardial infarction by 22%, stroke by 33% and cardiovascular death by 37%. For these reasons American Heart Association recommends that in the absence of contra indication, ACE inhibitors be administered to all diabetic patients. The recommendation that all diabetic patients maintain a BP of <130/80mmHg. National Kidney Foundation (NKF) recommends that diabetic patients with proteinurea >1g/day lower their BP goal to <125/75 mmHg. In long standing diabetic patients, who are more likely to have developed macro and microvascular disease, BP control appears to be a more important factor for prevention of cardiovascular events than glucose control.

7. Smoking Cessation: Smoking is an independent risk factor for developing Coronary Heart Disease, complete cessation should be the primary goal for all smokers, specially those with diabetes.

Initial Management of Myocardial Infarction in Diabetes Patient

Diagnosis upto 1/3 of patient with AMI have symptoms other than classical substernal chest pressure radiating to left arm or they have no symptoms at all until they develop congestive cardiac failure.

A typical presentation such as jaw/neck pain, epigastric pain associated with vomiting, isolated shortness of breath DKA are common.  Upto 35% will not have characteristics ECG ST Elevation indicating injury or Q wave indicating infarction. Diabetic patient often have renal insufficiency, which may falsely elevate cardiac markers.

The following assist in diagnosis of Acute Myocardial Infarction detection of a rise in cardiac biomarkers (tropronin) and at least one of the following.

1. Symptoms of ischemia
2. ECG changes indicative of new ischemia
3. Development of pathological Q waves on ECG
4. Imaginary evidence of a new loss of viable myocardium / new Regional Wall Motion Abnormality.

Management Strategies in STEMI

Emergent target vessel reperfusion with fibrinolytic therapy or primary percutaneous intervention (PCI) is the standard care for management of STEMI. Alteplase and reteplase should be used with adjuctive heparin, where as the non specific fibrinolytic agents such as streptokinase and urokinase) can be used without heparin. Adjuctive aspirin 42% reduction in vascular mortality.

Current guidelines patient with STEMI presentation

Symptoms > 3 hrs duration, when transfer to a PC I centre is possible within 60min of presentation a reperfusion strategy using PCI is more beneficial than fibrinolytic therapy.

In diabetic patient presenting with STEMI, PCI with coronary stenting is preferred over PCI alone since PCI with coronary stenting reduce the composite end point of death, reinfarction, disabling stroke and need for revascularization. Comparing primary PCI with bare metal stent (BMS) and drug eluting stent (DES) there were lower rates of repeat revascularization and acute stent thrombosis and recurrent myocardial infarction with BMS.

Medical management of patient presenting with STEMI should include immediate therapy with Aspirin 325 mg and unfractionated heparin (UFH) or LMWH, clopidogrel is reasonable as a 300mg oral loading dose for patient who have received fibrinolytic therapy or have not received reperfusion therapy and clopidogril is recommended as a 600mg oral loading dose for patient undergoing PCI GP II b / IIIa receptor antagonist can be given enroute or in the catheterization laboratory.

Management Strategies in NSTEMI

The target vessel in patient with NSTEMI is usually not completely occluded for supplies a small territory.  The corners stone of therapy is rapid platelet inhibition and plaque stabilization, followed by medical management among low risk patient and an early invasive strategy for high risk patients.

Hemodynamically unstable patient with NSTEMI should receive emergent primary PCI.

All patient with NSTEMI should receive LMWH in the absence of Contraindications, Subcutaneous enoxaparin in non Qware coronary events significantly reduced the incidence of death, recurrent MI and angina at 30 days also 30 day mortality was significantly lower in diabetic patient using GPIIb / IIIa receptor inhibitors.

Surgical Revascularisation

Emergent coronary artery bypass graft (CABG) in setting  of acute myocardial infarction. CABG as the preferred revascularization strategy in diabetic patient with unstable angina and multivessel coronary disease.  Triple vessel disease and either clinically severe angina or objective evidence of marked myocardial ischemia requiring revascularization.

CABG was limited to 81% of diabetic patient receiving internal mammary graft  cardiac mortality was 2.9% when internal mammary grafts were used versus 18.2% when only saphenous vein graft were used (similar to PTCA).

Glycemic Control

DIGAMI study the diabetic insulin gluco infusion in acute myocardial infarction initial insulin glucose infusion followed by multidose insulin treatment for 3 months.

NSTEMI recommend in acute glucose management (in first 3 days) to keep preprandial <110 mg/dl and maximum glucose < 180 my/dl.

Longterm Management (Periinfartion) guidelines:

Patient with Diabetic surviving MI have higher late mortality, which is mainly related to recurrent MI and the development of heart failure

1. Aspiring – a chewed 325 mg aspirin can be administered as soon as possible after presentation and 162-325 to be continued for atleast 1 month for patient with BMS and 3-6 months for patient receiving DES.  Then patient can be continued indefinitely at 75 to 162 mg / day of aspirin.
2. Clopedogel: 75 mg / day clopidogrel be administered when aspirin contraindicated because of hypersensitivity and major Gastro intestinal intolerance.

In NSTEMI, conservative approach, clopidogrel added to aspirin as soon as possible on admission and administered for at least 12 months.  When PCI planned clopidogel should be taken a minimum of 1 month (ideally upto 12 months) for BMS and 12 months of DES.

When elective CABG planned, clopidogrel should be withheld for 5-7 days.

3. UFH and LMWH – Anti coagulation with S.C. LMWH or I.V. Unfractionate Heparin be added to antiplatelet therapy with aspirin clopidogel throughout the reminder of the hospitalization or for 7 days.

Enoxaporin is superior to UFH as an anticoagulant in patient with unstable angina or NSTEMI unless CABG is planned within 24 hrs.

4. GP IIb / III a Antagonist

The AHA recommended that platelet GPIIb/IIIa antagonist to be administered in addition to Aspirin, and heparin, to patient in whom catheterization and PCI are planned or just before PCI.

Epitifibatide or Tirofiban can be administrated in addition to Aspirin, LMWH, to patient with continuing ischemia with an elevated troponin, or with other high risk features.

5. b-Blockers: Oral b blockers can be administered to all patients in absence of Contra indications I.V. b blockers indicated in patients with hypertension or tacharrythimias as with contra indications in potential severe heart failure, cardiogenic shock or high degree AV block
6. ACE inhibitors administer to all patient with Diabetes
7. Statins and other lipid lowering agents in all post ACS patient including post revascularization patient, treating to a target LDL cholesterol level < 100 mg/dl, Fibrate should be administrated if HDL cholesterol is < 40mg/dl occurring as an isolated finding or in combination with other lipid abnormalities and TG > 200mg / dl ; Diet should begin 24-96 hrs after administration
8. Nitroglycerin If anginal discomfort lasting > 2-3 mins should prompt the patient to discontinue the activity if pain doesnot subside immediately patient should be instructed to take nitroglycerine.  If Nitroglycerine doesnot provide relief within 5 minutes, prompt the patient to seek immediate medical attention preferably via ambulance.
9. Other agents: Angiotensin receptor blockers are an appropriate alternative in patient with MI complicated by systolic LV dysfunction. Candesartan in heart failure assessment found a reduction in cardio vascular death and hospital admissions for heart failure independent of ejection fraction or baseline treatment.  The selective aldosterone receptor blocker eplerenone is used in patients with acute MI complicated by systolic left ventricular dysfunction and either heart failure or diabetes.

NOTE:

            In the setting of STEMI, emergent pci is preferable over fibronolysis, especially for those patients beyond the first 3 hrs of symptoms.

            Diabetes with NSTEMI will undergo coronary angiography and possibly primary PCI within the first 48 hrs of presentation.

            In diabetic patient with unstable angina, CABG (with left internal mammary artery grafting) is superior to multivessel PCI.

REFERENCE:

            Clinical Practice Recommendations ADA