1. STEMI ST ELEVATED MYOCARDIAL INFARCTION

2. TREATMENT Short term desired outcomes: Early restoration to the infarct related artery, to prevent the spread of MI, or prevent complete occlusion and MI. Prevention of death and other MI complications. Prevention of Coronary artery re-occlusion. Relief of ischemic chest discomfort. Long-term desired outcomes: Control of CV risk factors. Prevention of additional CV risk factors. (Re-infarction, stroke, HF) Improving the quality of life. 2

3. GENERAL APPROACH TO TREATMENT General treatment measures for all STE MI and high- and intermediate- risk NSTE ACS patients include: - Admission to hospital. - Oxygen administration (if oxygen saturation is low, less than 90%). - Continuous ST-segment monitoring for arrhythmias and ischemia. - Frequent measurement of vital signs. - Bedrest for 12 hours in hemodynamically stable patients. - Avoidance of the Valsalva maneuver (prescribe stool softeners routinely). - Pain relief (morphine sulphate) 3

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5. TIMI RISK SCORE FOR NSTE ACS One point is assigned for each of the seven medical history and clinical presentation findings. The point total is calculated and the patient is assigned a risk for experiencing the composite end point of death, myocardial infarction, or urgent need for re-vascularization as follows: Age 65 years or olderAge 65 years or older Three or more CHD risk factors: smoking, hypercholesterolemia, hypertension, diabetes mellitus, family history of premature CHD death/eventsThree or more CHD risk factors: smoking, hypercholesterolemia, hypertension, diabetes mellitus, family history of premature CHD death/events Known CAD (50% or greater stenosis of at least one major coronary artery on coronary angiogram)Known CAD (50% or greater stenosis of at least one major coronary artery on coronary angiogram) Aspirin use within the last 7 daysAspirin use within the last 7 days Two or more episodes of chest discomfort within the last 24 hoursTwo or more episodes of chest discomfort within the last 24 hours ST-segment depression 0.5 mm or greaterST-segment depression 0.5 mm or greater Positive biochemical marker for infarctionPositive biochemical marker for infarction 0-2 points (Low risk) 3-4 (Medium risk) 5-7 (High risk) One point is assigned for each of the seven medical history and clinical presentation findings. The point total is calculated and the patient is assigned a risk for experiencing the composite end point of death, myocardial infarction, or urgent need for re-vascularization as follows: Age 65 years or olderAge 65 years or older Three or more CHD risk factors: smoking, hypercholesterolemia, hypertension, diabetes mellitus, family history of premature CHD death/eventsThree or more CHD risk factors: smoking, hypercholesterolemia, hypertension, diabetes mellitus, family history of premature CHD death/events Known CAD (50% or greater stenosis of at least one major coronary artery on coronary angiogram)Known CAD (50% or greater stenosis of at least one major coronary artery on coronary angiogram) Aspirin use within the last 7 daysAspirin use within the last 7 days Two or more episodes of chest discomfort within the last 24 hoursTwo or more episodes of chest discomfort within the last 24 hours ST-segment depression 0.5 mm or greaterST-segment depression 0.5 mm or greater Positive biochemical marker for infarctionPositive biochemical marker for infarction 0-2 points (Low risk) 3-4 (Medium risk) 5-7 (High risk) 5

6. NON PHARMACOLOGIC THERAPY Treatment of Choice for patients presenting with STE MI who present within 12 hours of symptom onset: Early re-perfusion therapy with primary PCI of the infarct artery. The patient is taken from the emergency department to the cardiac catheterization laboratory and undergoes coronary angiography with either balloon angioplasty or placement of a bare metal or drug- eluting intra-coronary stent in the artery associated with the infarct. This is very vital. Every minute delay results in additional myocardial cell damage that may be irreversible. 62% of patients with STE MI are treated with primary PCI; 18% are treated with fibrinolytic. Intracranial hemorrhage (ICH) and major bleeding risks from primary PCI are lower than the risks of severe bleeding events following fibrinolysis. Less mortality with PCI than Fibrinolysis. Patients undergoing PCI should be taking acetylsalicylic acid. 6

7. EARLY PHARMACOTHERAPY FOR STEMI According to the ACCF/AHA STE MI practice guidelines, in addition to re-perfusion therapy, other early pharmacotherapy that all patients with STE MI and without contraindications should receive within the first day of hospitalization, and preferably in the emergency department, are: Intranasal oxygen (if oxygen saturation is low), Intranasal oxygen (if oxygen saturation is low), Sublingual (SL) nitroglycerin (NTG), Sublingual (SL) nitroglycerin (NTG),nitroglycerin ASA (acetylsalicylic acid) ASA (acetylsalicylic acid) P2Y 12 inhibitor ( clopidogrel, prasugrel, or ticagrelor depending on re-perfusion strategy) P2Y 12 inhibitor ( clopidogrel, prasugrel, or ticagrelor depending on re-perfusion strategy)clopidogrel, Anticoagulation with bivalirudin (reversible direct thrombin inhibitor) Anticoagulation with bivalirudin (reversible direct thrombin inhibitor) Unfractionated heparin (UFH), (*for patients undergoing primary PCI they should receive a GPIIb/IIIa inhibitor) Unfractionated heparin (UFH), (*for patients undergoing primary PCI they should receive a GPIIb/IIIa inhibitor)heparin Enoxaparin (low molecular weight heparin) Enoxaparin (low molecular weight heparin) Fondaparinux (factor Xa inhibitor). Fondaparinux (factor Xa inhibitor). Oral beta blockers, for patients without cardiogenic shock. Oral beta blockers, for patients without cardiogenic shock. Morphine for patients with refractory angina as an analgesic and ventilator to lower preload. Morphine for patients with refractory angina as an analgesic and ventilator to lower preload. Within 24 hours, patients with an LVEF less than 40% should receive ACEI 7

8. Fibrinolytic therapy Contraindicated in ICH patients. Contraindicated in ICH patients. Given if PCI is not possible Given if PCI is not possible If patient can’t take fibrinolytics and can have no PCI ——> UFH for up to 8 days. If patient can’t take fibrinolytics and can have no PCI ——> UFH for up to 8 days. Most patients present after 12 hours of symptom onset, so they can neither receive PCI nor fibrinlytics. “door to needle” time should be 30 mins. Most patients present after 12 hours of symptom onset, so they can neither receive PCI nor fibrinlytics. “door to needle” time should be 30 mins. Fibrin specific agents: alteplase, reteplase, or tenecteplase. (first line agents) Fibrin specific agents: alteplase, reteplase, or tenecteplase. (first line agents)alteplase Non–fibrin-specific agent: streptokinase. Non–fibrin-specific agent: streptokinase. Risk of ICH is higher with fibrin specific agents than streptokinase. Risk of ICH is higher with fibrin specific agents than streptokinase. Systemic bleeding higher with streptokinase>alteplase>tenecteplase Systemic bleeding higher with streptokinase>alteplase>tenecteplase 8

9. ASPIRIN Is the preferred antiplatelet agent in the treatment of all ACSs Works by inhibiting the synthesis of Thromboxane A2 through an irreversible inhibition of platelet cyclooxygenase-1. In patients undergoing PCI, ASA prevents acute thrombotic occlusion during the procedure. In patients receiving fibrinolytics, ASA reduces mortality, and its effects are additive to fibrinolysis alone. Additionally, in patients undergoing PCI, ASA, in addition to a P2Y 12 inhibitor, reduces the risk of stent thrombosis. Nonsteroidal antiinflammatory agents other than ASA, as well as cyclooxygenase-2 (COX-2) selective antiinflammatory agents, should be discontinued at the time of STE MI secondary to increased risk of death, reinfarction, HF, and myocardial rupture. Most frequent side effects with ASA: 1. Dyspepsia 2. Bleeding (gi) 3. Nausea 9

10. Platelet P2Y 12 Inhibitors ClopidogrelClopidogrel, prasugrel, and ticagrelor block a subtype of ADP receptor, the P2Y 12 receptor, on platelets, preventing the binding of ADP to the receptor and subsequent expression of platelet GP IIb/IIIa receptors, reducing platelet activation and aggregation. Clopidogrel **Both prasugrel and ticagrelor are more potent ADP inhibitors than clopidogrel. clopidogrel **Prasugrel has the fewest significant drug–drug interactions. **The production of clopidogrel’s active metabolite and consequently its antiplatelet effect is reduced by moderate and strong inhibitors of CYP2C19, while ticagrelor’s concentration is reduced by strong inhibitors of CYP3A. clopidogrel Prasugrel is not as dependent on CYP2C19 genotype for its conversion to the active metabolite and has a lower frequency of poor antiplatelet responsiveness. (While clopidogrel depends genetic make up) Two subgroups of patients do not have an increased bleeding risk with prasugrel compared with clopidogrel and have even greater benefit, namely, patients undergoing primary PCI for STE MI and patients with a history of diabetes mellitus clopidogrel

11. Prasugrel is contraindicated if there is history of 1. prior stroke or 2. transient ischemic attack (TIA) because there’s an increased risk of ICH. Prasugrel is contraindicated if there is history of 1. prior stroke or 2. transient ischemic attack (TIA) because there’s an increased risk of ICH. Prasugrel compared with Clopidogrel, reduced MI and CV death more, but also increased the risk of bleeding. ( in the setting of stemi,nstemi) Prasugrel compared with Clopidogrel, reduced MI and CV death more, but also increased the risk of bleeding. ( in the setting of stemi,nstemi) Patients older than 75 years and those weighing less than 60 kg (132 lb) are at increased risk of bleeding with prasugrel compared with clopidogrel. Ticagrelor significantly reduced the rate of the CV death, MI, stroke, and stent thrombosis compared with clopidogrel. The frequency with non coronary artery bypass grafting bleeding was, nevertheless, increased compared to clopidogrel. Even if prasugrel and ticagrelor are more efficacious than clopidogrel they also have increased risk of bleeding. 11

12. Clopidogrel should NOT be used in 1. patients with active pathologic bleeding 2. clopidogrel ineffectiveness (e.g., poor metabolism, stent thrombosis during clopidogrel therapy) or 3. drug–drug interactions (e.g., avoid moderate and strong CYP2C19 inhibitors); Prasugrel should NOT be used in patients with 1. active pathologic bleeding or 2. a history of transient ischemic attack or stroke. Ticagrelor should NOT be used in patients with 1. active pathologic bleeding or 2. a history of intracranial hemorrhage (ICH) 3. concomitant maintenance aspirin dose above 100 mg should be avoided. Consider a. patient compliance (dosed twice daily), unique adverse effects (e.g., dyspnea), and b. potential drug–drug interactions (e.g., avoid strong CYP3A inhibitors/inducers). **if a patient subsequently goes on to receive CABG surgery, the drugs should be held for at least 5- 7 days if the surgery can be delayed. 12

13. Most frequent side effects of clopidogrel, prasugrel and ticagrelor (2-4%): 1. nausea 2. vomiting 3. diarrhea Most frequent side effects of clopidogrel, prasugrel and ticagrelor (2-4%): 1. nausea 2. vomiting 3. diarrhea Thrombotic thrombocytopenic purpura (TTP) has been reported with clopidogrel. Thrombotic thrombocytopenic purpura (TTP) has been reported with clopidogrel. Use of ticagrelor is associated with 1. dyspnea and, rarely 2. ventricular pauses and 3. bradyarrhythmias. Use of ticagrelor is associated with 1. dyspnea and, rarely 2. ventricular pauses and 3. bradyarrhythmias. Clopidogrel is used in patients with STEMI without reperfusion therapy, or fibrinolysis. Ticagrelor is also used nowadays. Clopidogrel is used in patients with STEMI without reperfusion therapy, or fibrinolysis. Ticagrelor is also used nowadays.

15. Anti-platelet drugs: Glycoprotein IIb/IIIa Receptor Inhibitors GP IIb/IIIa receptor inhibitors block the final common pathway of platelet aggregation: cross-linking of platelets by fibrinogen bridges between the GP IIb and IIIa receptors on the platelet surface. In patients with STE MI undergoing primary PCI who are treated with UFH, abciximab (IV or intracoronary administration), eptifibatide, or tirofiban may be administered. The major adverse effect is bleeding. This is increased with CKD GP IIb/IIIa inhibitors should not be administered to patients with a prior 1. history of hemorrhagic stroke or 2. recent ischemic stroke. Eptifibatide is contraindicated in patients dependent on dialysis and requires a reduced infusion dose in patients with creatinine clearance (CrCl) less than 50 mL/min. Thrombocytopenia occurs in 5% of abciximab patients.

16. BETA BLOCKERS should be administered early, and continued indefinitely. should be administered early, and continued indefinitely. β 1 -Blockade produces a reduction in heart rate (HR), myocardial contractility, and blood pressure (BP), decreasing myocardial oxygen demand, consequently by increasing filling time there’ll be improved ventricular filling and coronary artery perfusion. As a result of these effects, β-blockers reduce the risk for 1. recurrent ischemia, 2. infarct size 3. risk of reinfarction, and 3. occurrence of ventricular arrhythmias in the hours and days following MI. β 1 -Blockade produces a reduction in heart rate (HR), myocardial contractility, and blood pressure (BP), decreasing myocardial oxygen demand, consequently by increasing filling time there’ll be improved ventricular filling and coronary artery perfusion. As a result of these effects, β-blockers reduce the risk for 1. recurrent ischemia, 2. infarct size 3. risk of reinfarction, and 3. occurrence of ventricular arrhythmias in the hours and days following MI. The most serious side effects of β-blocker administration early in ACSs are 1. hypotension 2. acute HF 3. bradycardia 4. heart block

17. ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS Angiotensin-converting enzyme (ACE) inhibitors should be used in all patients with a STEMI without contraindications. ACE inhibitors decrease myocardial afterload through vasodilatation. For patients with ACEI intolerance, ARB’s can be used. Ideally we start on a short acting low dose ACEI, then once reaching the maintenance dose, we change to a long acting dose equivalent ACEI.

18. STATINS STATINS A high-intensity statin (either atorvastatin or rosuvastatin) should be administered to all patients prior to PCI (regardless of prior lipid-lowering therapy) to reduce the frequency of periprocedural MI (a Type IVa MI) following PCI. atorvastatinrosuvastatinatorvastatinrosuvastatin NITRATES NITRATES One SL NTG tablet should be administered every 5 minutes for up to three doses in order to relieve myocardial ischemia. Nitrates promote the release of nitric oxide from the endothelium, which results in venous and arterial vasodilation. Venodilation lowers preload and myocardial oxygen demand. Arterial vasodilation may lower BP, thus reducing myocardial oxygen demand. Arterial vasodilation also relieves coronary artery vasospasm, dilating coronary arteries to improve myocardial blood flow and oxygenation. Nitrates can reverse the vasoconstriction associated with thrombosis and coronary occlusion. Headache, flushing, tachycardia, hypotension are the most common side effects. There’s a contraindication if the patient is taking sildenafil, or phosphodiesterase inhibitor. 18

19. CALCIUM CHANNEL BLOCKERS used for relief of ischemic symptoms. used for relief of ischemic symptoms. CCB’s should be avoided in acute ACS unless 1. clear contraindication to beta blockers or 2. clear symptomatic need. CCB’s should be avoided in acute ACS unless 1. clear contraindication to beta blockers or 2. clear symptomatic need. Administration of an agent that lowers HRs, either diltiazem or verapamil, is preferred unless the patient has LV systolic dysfunction, bradycardia, or heart block, and then either amlodipine or felodipine is preferred. Nifedipine should be avoided because it has demonstrated reflex sympathetic activation, tachycardia, and worsened myocardial ischemia. diltiazemverapamilamlodipinefelodipine Nifedipinediltiazemverapamilamlodipinefelodipine Nifedipine 19

20. ALDOSTERONE ANTAGONISTS A mortality benefit was seen with eplerenone administration in all post-MI patients, provided multiple criteria were met. The criteria included : - Concomitant use of an ACE inhibitor, - Ejection fraction less than 40%, - Symptomatic heart failure or diabetes, - A creatinine clearance greater than 30 mL/min, - A potassium level less than 5 mEq/dL

22. Secondary prevention guidelines from the ACCF/AHA suggest that following MI, all patients without contraindication should receive and indefinite treatment of: 1. Acetylsalicylic acid 2. ACE inhibitor 3.”High-intensity” Statin, to prevent stroke, death, or recurrent infarctions. 4. B-blocker for at least 3 years. (patient without HF or EF<40%) 5. P2Y12 inhibitor should be used for 12 months for patients undergoing PCI. Clopidogrel should be continued for at least 14 days in patients with STE MI not undergoing PCI. Clopidogrel should be continued for at least 14 days in patients with STE MI not undergoing PCI. Clopidogrel For all patients with ACS, treatment and control of modifiable risk factors such as HTN, dyslipidemia, obesity, smoking, and DM are essential. 22

23. SECONDARY PREVENTION FOLLOWING MI The long-term goals following MI are to (a) control modifiable CHD risk factors; (b) prevent the development of systolic HF; (c) prevent recurrent MI and stroke; (d) prevent death, including sudden cardiac death; and (e) prevent stent thrombosis following PCI.