“Acute Coronary Syndrome” July 24, 2013

Item 72 A 78 year old man is evaluated in the ED with chest pain. The patient reports that the pain, which is present in the left substernal area, began at rest, and has been present for 12 hours. He reports no similar episodes of chest pain. Medical history is significant for hypertension and a 30-pack year history of ongoing tobacco use. His only medication is nifedipine. On PE, temperature is 37.90C, BP 130/80 mm Hg, pulse rate is 72/minute and respiration rate is 12/min. BMI is 28. A normal carotid upstroke without carotid bruits is noted, jugular venous pulsations are normal and S1 and S2 are heard without murmurs. Lung fields are clear, distal pulses are normal and no peripheral edema is present.

Item 72 (Con’t) Serum creatinine kinase level is 500 units/L and troponin I level is 26 ng/mL. Lab findings are otherwise normal. EKG shows sinus rhythm at 70/min; 2 mm ST-segment elevation in leads II, III and aVF; and 1 mm ST segment depression in leads V2 and V3. He is taken to the cardiac cath lab and found to have single vessel coronary disease with severe stenosis of the proximal left anterior descending coronary artery.

Item 72 (Con’t) Which of the following is the most appropriate treatment? Coronary artery bypass surgery Intracoronary thrombolytic therapy Medical therapy Primary percutaneous coronary intervention

STEMI Care and Time to Treatment Goals IIa IIb III 2013 ACC/AHA Guideline A Primary PCI is the recommended method of reperfusion when it can be performed in a timely fashion by experienced operators. JACC 2013;61:e1-63

STEMI Care and Time to Treatment Goals IIa IIb III 2013 ACC/AHA Guideline A Reperfusion therapy should be administered to all eligible patients with STEMI with symptom onset within the prior 12 hours JACC 2013;61:e1-63

STEMI Care and Time to Treatment Goals IIa IIb III 2013 ACC/AHA Guideline B Reperfusion therapy is reasonable for patients with STEMI within the prior 12 to 24 hours who have clinical and/or ECG evidence of ongoing ischemia. Primary PCI is the preferred strategy in this population JACC 2013;61:e1-63

Item 38: MKSAP A 54 year old man is evaluated in the ED for acute coronary syndrome that began 30 minutes ago. He has type 2 diabetes mellitus and hypertension. He reports no history of bleeding or stroke. He has a remote history of peptic ulcer disease for which he takes no medications. Medications are lisinopril and glipizide. On physical exam, he is afebrile, BP is 160/90 mm Hg, pulse rate is 80 and respiration 12/min. CV examination reveals a normal S1 and S2 without an S3 and no murmurs. Lung fields are clear.

MKSAP: Item 38 Serum troponin and creatinine kinase levels are pending. Hematocrit is 42% and platelet count is 220,000/L EKG shows 3 mm ST segment elevation in leads V2 through V4 and a 1 mm ST segment depression in leads II, III and aVF. A chest radiograph is normal. There is no cardiac cath lab present at the hospital and it would take approximately 1.5 hours to transfer the patient to the closest facility that performs PCI. -blockers, unfractionated heparin, clopidogrel and aspirin are initiated.

MKSAP: Item 38 Which of the following is the most appropriate management? Abciximab and thrombolytic therapy Await the results of troponin and CK Thrombolytic therapy Transfer for primary PCI

STEMI Care and Time to Treatment Goals IIa IIb III 2004 ACC/AHA Guideline B If the symptom duration is within 3 hours and the expected door to balloon time minus the expected door to needle time is: Within 1 hour, primary PCI is preferred Greater than 1 hour, fibrinolytic therapy is generally preferred. Circulation 2004;110:588-636

Target Door to Balloon Time Door to Balloon Time for Transfer and Direct Arrival Patients, National CV Data Registry (NCDR) Am Heart J 2011;161:76-83 210 180 Transfer PCI 150 120 Target Door to Balloon Time Time (Minutes) Direct PCI 90 60 30 Year 2005 QI 2005 Q3 2006 Q1 2006 Q3 2007 Q1 2007 Q3

Transfer and Direct PCI Door to Balloon Time Am Heart J 2011;161:76-83 50 90 minutes 40 Direct PCI = 79 min (n=86,382) 30 63.4% Percentage of Patients 20 Transfer PCI = 149 min 10 (n=29,248) 9.7% 1 2 3 4 5 6 Door to Balloon Time (hours)

STEMI Care and Time to Treatment Goals IIa IIb III 2013 ACCF/AHA Guideline B Immediate transfer to a PCI-capable hospital for primary PCI is recommended strategy for STEMI patients who initially arrive at or are transported to a non-PCI-capable hospital with a FMC-to-device time goal of 120 minutes or less.

STEMI Patient, First Medical Contact PCI Capable Hospital Non-PCI Capable Hospital Door In Door Out (DIDO) ≤30 mins FMC* to Device Time ≤120 min Anticipated FMC* to Device Time ≥120 min FMC* to Device Time ≤90 mins Transfer for Primary PCI Cath Lab for PCI Thrombolytic Therapy within 30 mins *FMC: First Medical Contact JACC 2013;61:e1-63

Acute Coronary Syndrome Definition A constellation of clinical symptoms due to acute myocardial ischemia Circulation 2011,123:e426-e579

Myocardial Infarction Definition Myocardial necrosis (or myocardial cell death) due to prolonged ischemia. Third Universal Definition of MI Circulation 2012,126:2020-2035

Causes of Acute Coronary Syndrome Atherosclerosis Compression - Muscle bridges - Aortic aneurysm Congenital - Anomalous origin - Anomalous course - Single artery Drugs - Sumatriptan - Ergot alkaloids - Cocaine Embolic - Vegetations - Tumor - Calcium Aortic dissection Vasospasm Intimal proliferation - Fibromuscular hyperplasia - Radiation Trauma Arteritis

3 Major Causes of ACS Atherosclerosis Atherosclerosis Atherosclerosis

Types of Myocardial Infarction Type 1: Spontaneous MI due to plaque rupture, ulceration, fissuring, erosion, etc. Type 2: MI secondary to an ischemic imbalance Type 3: MI resulting in death and biomarkers are unavailable Type 4a: MI related to PCI Type 4b: MI related to stent thrombosis Type 5: MI related to CABG Circulation 2012;126:2020-2035

MI Type 1

Plaque Rupture

Healed Plaque

Erosion

Atherothrombosis: A Generalized and Progressive Process Atherothrombosis, or thrombosis superimposed on underlying atherosclerosis, is the usual underlying disease process for acute coronary syndromes.1 Everyone has atherosclerotic lesions from childhood on.2 Early atherosclerotic changes, such as fatty streaks (consisting primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells) are not clinically apparent. As atherosclerosis evolves over time, the lesions progress to atheromas, in which a lipid-laden core is separated from the lumen by a fibrous cap. Once the lumen narrows, symptoms such as angina on effort and intermittent claudication may develop, depending on the affected vascular bed.2 Unstable plaque (ie, having a large lipid core and a thin cap infiltrated with macrophages and lymphocytes) is associated with plaque rupture or fissure, hemorrhage, and thrombosis.1 Rupture of the cap permits blood from the arterial lumen to enter the core and come in contact with highly thrombogenic tissue factor and collagen from the vessel wall. Formation of platelet-rich and fibrin-rich thrombi can partly or totally occlude arteries. Note that the neat progression shown on the slide does not occur in all cases. Even small lesions may rupture; in fact, small lesions may be responsible for ACS in two thirds of patients.3 Atherothrombosis can result in acute coronary syndromes, ischemic stroke, transient ischemic attack, sudden cardiac death, or acute limb ischemia.1 Rauch U, Osende JI, Fuster V, et al. Thrombus formation on atherosclerotic plaques: pathogenesis and clinical consequences. Ann Intern Med. 134;224-238. Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. Circulation. 1995;92:1355-1374. Fuster V, Fayad ZA, Badimon JJ. Acute coronary syndromes: biology. Lancet. 1999;353(suppl II):5-9. 25

Progressive Narrowing of the Arterial Lumen Vessel Lumen Lipid Core Clot Atherosclerotic Vessel Progressive Narrowing (Time) Thrombotic Occlusion

Plaque Rupture and Atherothrombosis Vessel Lumen Lipid Core Thrombus Atherosclerotic Vessel Plaque Rupture Platelet Adhesion Activation and Aggregation Thrombus Formation Thrombotic Occlusion MI Stroke Vascular Death Am J Med 1996;101:199-209

Most MI’s Arise From Smaller Stenoses Baseline Study Circulation 1988;78:1157-1166

Most MI’s Arise From Smaller Stenoses 13 Days Later Circulation 1988;78:1157-1166

Most MI’s Arise From Smaller Stenoses Baseline Study Circulation 1988;78:1157-1166

Most MI’s Arise From Smaller Stenoses 2 months later Circulation 1988;78:1157-1166

Most MI’s Arise From Smaller Stenoses Circulation 1995;92:657-671 80 68% Asymptomatic 60 Symptomatic MI Patients (%) 40 18% 20 14% < 50% 50-70% > 70% Percentage Stenosis

Acute Coronary Syndrome Circulation 2002;105:2000-2004 PCI With Stent Systemic Medical Therapy to Stabilize Plaque Aspirin Clopidogrel/Prasugrel/Ticagrelor Statins ACE Inhibitors/ARBs Beta Blockers Smoking Cessation

Multiple Plaques in ACS Circulation 2002;106:804-808 79% of patients had >1 plaque ruptured 40 29% 30 25% 21% MI Patients (%) 20 12.5% 10 7.5% 4.5% Culprit Lesion 1 2 3 4 5 Number of Ruptured Plaques in Addition to Culprit Lesion Detected by IVUS

The Asymptomatic Progression of CAD Initial Presentation 62% MEN (65.8 years) 46% ACS or Sudden Cardiac Death WOMEN (70.4 years) 10 20 30 40 50 60 70 Levy D, Textbook of CV Medicine 1998 AHA: Heart Disease and Stroke Statistics-2006 Update

Ventricular Fibrillation

Ventricular Fibrillation and Survival 1.0 0.8 0.6 Proportion Surviving 0.4 0.2 1 2 3 4 5 6 7 8 9 10 Minutes

Ventricular Fibrillation

Deaths due to Acute MI In-hospital mortality had improved significantly 1960’s – prior to introduction of CCUs, in-hospital mortality averaged ~25-30%. 1980’s – CCU, pre-reperfusion era ~16% 1990 - 2000’s – era of fibrinolysis, coronary interventions, those who participated in clinical trials, one month mortality is ~4-6% Eur HJ 2208;29:2909-2945

Mortality in Acute MI 21% 8% 52% 19% Pre-Hospital 21% 24 Hours In-Hospital 8% 52% 48 Hours In-Hospital 30 Days 19% One-half of all deaths occur “in the field” within one hour after symptom onset

Acute Coronary Syndrome ST elevation myocardial infarction Non-ST elevation myocardial infarction Unstable Angina

Hospitalizations in the US due to ACS Acute Coronary Syndromes 1.57 Million Hospital Admissions 79% 21% UA/NSTEMI STEMI Approximately 2.3 million Americans will present to the emergency department with chest pain due to acute coronary syndrome.[1] Of these patients, twice as many (1.43 million) will be admitted and diagnosed with unstable angina (UA) or non–ST-segment elevation myocardial infarction (NSTEMI; also known as non–Q-wave MI) compared with 829,000 patients who will be diagnosed with ST-segment elevation MI (STEMI; also known as Q-wave MI).[1] According to the American Heart Association, 1.1 million new or recurrent coronary attacks (defined as MI or coronary heart disease) will occur this year.[2] Of these cases, 650,000 will be first cases and 450,000 will be recurrent cases. Additionally, about 150,000 new cases of UA will be diagnosed.[2] National Center for Health Statistics. 1999 National Hospital Discharge Survey: Annual Summary with Detailed Diagnosis and Procedure Data. Hyattsville, Maryland: US Dept of Health and Human Services; 2001: Series 13, No. 151. American Heart Association. 2002 Heart and Stroke Statistical Update. 2001. 0.33 million admissions 1.24 million admissions 0.57 million NSTEMI 0.67 million UA Heart Disease and Stroke Statistics 2007 Update Circulation 2007;115:69-171 ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update 42

Incidence Rate (No. of cases/100,000 per person-year) Rates of Acute MI, 1999 - 2008 JACC 2013;61e7 300 MI 250 200 Non-STEMI 150 Incidence Rate (No. of cases/100,000 per person-year) 100 STEMI 50 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Year

Acute Coronary Syndrome Typical Symptoms: Central chest pain Chest discomfort Chest pressure Chest tightness Heaviness Cramping or burning sensation Indigestion or heartburn Call 911

Acute Coronary Syndrome Symptoms of Acute MI Hospitalized Recommended Discouraged Call 911 Ambulance Transport Self Transport JACC 2008;51:210-247

Percentage of Patients with ACS Calling 911 National Registry of MI -2 Emergency Medical System 53% Survey of confirmed ACS patients in 20 US communities Emergency Medical System 10-48% (23%) Driven by someone else 60% 16% Drove themselves Circulation May, 2011 e440

Acute Coronary Syndrome Physical signs: No physical signs diagnostic of Acute MI Activation of autonomic nervous system Pallor Sweating Hypotension or narrow pulse pressure Irregularities in heart rate, bradycardia, tachycardia Third heart sound Basal rales

Acute Coronary Syndrome Symptoms of Acute MI Ambulance Self Transport 12-Lead ECG Hospital/ED Obtained and Interpreted <10 mins 12 Lead-ECG JACC 2008;51:210-247

Hospitalizations in the US due to ACS Acute Coronary Syndrome 1.57 Million Hospital Admissions 79% 21% STEMI UA/NSTEMI Approximately 2.3 million Americans will present to the emergency department with chest pain due to acute coronary syndrome.[1] Of these patients, twice as many (1.43 million) will be admitted and diagnosed with unstable angina (UA) or non–ST-segment elevation myocardial infarction (NSTEMI; also known as non–Q-wave MI) compared with 829,000 patients who will be diagnosed with ST-segment elevation MI (STEMI; also known as Q-wave MI).[1] According to the American Heart Association, 1.1 million new or recurrent coronary attacks (defined as MI or coronary heart disease) will occur this year.[2] Of these cases, 650,000 will be first cases and 450,000 will be recurrent cases. Additionally, about 150,000 new cases of UA will be diagnosed.[2] National Center for Health Statistics. 1999 National Hospital Discharge Survey: Annual Summary with Detailed Diagnosis and Procedure Data. Hyattsville, Maryland: US Dept of Health and Human Services; 2001: Series 13, No. 151. American Heart Association. 2002 Heart and Stroke Statistical Update. 2001. 1.24 million Admissions per year 0.33 million Admissions per year Heart Disease and Stroke Statistics 2007 Update Circulation 2007;115:69-171 ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update 49

Atherosclerotic plaque Acute Coronary Syndromes Pathophysiology Large Fissure Small Fissure Mural thrombus (unstable angina/ non-ST elevation MI) Occlusive thrombus (ST Elevation MI) Thrombus Lipid Pool Macrophages Stress, tensile, internal Shear forces, external Fissure Atherosclerotic plaque Plaque rupture Fuster V et al. NEJM. 1992; 326: 310-318. Davies MJ et al. Circulation. 1990; 82 (Suppl II): II-38, II-46.

TIMI Flow Grade TIMI 0 Complete Occlusion TIMI 1 TIMI 2 TIMI 3 Penetration of obstruction by contrast but no distal perfusion TIMI 2 Perfusion of entire artery but delayed flow TIMI 3 Full perfusion, normal flow

ST elevation = coronary artery is completely occluded Myocardial Ischemia Blood Supply Oxygen Demand TIMI 0 Flow Heart Rate Blood Pressure Inotropicity ST elevation = coronary artery is completely occluded = TIMI 0 blood flow

ST Elevation MI Hours “Time is Muscle” Benefit (%) Circulation 1992;85;2311-2315 100 80 60 Benefit (%) “Time is Muscle” 40 20 1 2 3 4 5 6 7 8 9 10 11 12 Hours

The 12-Lead ECG The 12-lead ECG is the only modality that can best identify the presence of a completely occluded coronary artery

Acute Coronary Syndrome Diagnostic and Therapeutic Pathways in Patients With and Without ST-Segment Elevation Acute Coronary Syndrome ECG ST Elevation No ST Elevation Aspirin, clopidogrel, UFH or LMWH, 2B/3A antagonists b-blockers, nitrates Thrombolysis, PCI Hamm CW et al. Lancet. 2001;358:1533-1538. 2002 ACC/AHA UA/NSTEMI Guideline Update. Available at: www.acc.org

Normal ECG

Acute Coronary Syndrome ST Elevation MI

Acute Coronary Syndrome ASA Chest Pain

Aspirin Give ASA as soon as possible unless there is GI bleed or patient is allergic to aspirin Dose 162 - 325 mg one dose Aspirin should be chewable or soluble If patient cannot take ASA due to nausea or GI disorder, use ASA suppositories Other than ASA, do not make the mistake of giving NSAID such as Motrin, Naprosyn, Celebrex, etc since NSAID increases mortality, re-infarction, myocardial rupture, CHF, and HBP JACC 2007;50:652-726

Acute Coronary Syndrome ASA Chest Pain NTG Arrival in ED ECG within 10 minutes ST Elevation NTG NTG NTG

ST Segment Elevation Baseline ECG

ST Segment Elevation After NTG

ST Segment Elevation Baseline ECG After NTG

ST Segment Elevation Baseline

ST Segment Elevation After NTG

ST Segment Elevation Baseline After NTG

Nitroglycerin For relief of chest pain, give NTG up to 3 doses at 3-5 minute intervals until pain is relieved or blood pressure is low Dose of NTG is 0.4 mg sublingual tablet or spray JACC 2007;50:652-726

Nitroglycerin Do not give if: Taking PDE Inhibitors for erectile dysfunction sildenafil (Viagra, Revatio) 24 h taladafil (Cialis, Adcirca) 48 h vardenafil (Levitra) ? Systolic BP <90 mm Hg or there is a drop of >30 mm Hg below baseline BP Bradycardia of <50 beats per minute Tachycardia of >100 beats per minute Suspected right ventricular MI JACC 2007;50:652-726

ST Elevation MI Thrombolytic Therapy Primary PCI Chest Pain ASA Chest Pain NTG ECG within 10 minutes ST Elevation NTG Self-Transport: Door to Needle <30 mins Self-Transport: Door to Balloon <90 mins NTG EMS Transport: <30 mins NTG EMS transport: <90 mins Thrombolytic Therapy Primary PCI

Acute Inferior MI Thrombolytic Therapy

Post Thrombolytic Therapy One Hour Later

Initial ECG Thrombolysis: One Hour Later

Thrombolysis No contraindication to thrombolysis Best results within 2 hours after onset of symptoms Hemodynamically stable: Not in cardiogenic shock or CHF or with mechanical complications of AMI

Contraindications to Thrombolysis Relative Contraindications History of chronic severe, poorly controlled hypertension Severe uncontrolled hypertension (SBP >180 mm Hg or DBP >110 mm Hg) History of prior ischemic stroke >3 mos, dementia or IC pathology Traumatic or prolonged (>10 mins) CPR or major surgery <3 weeks Recent (2-4 weeks) internal bleeding Pregnancy Active peptic ulcer Current use of anticoagulants Absolute Contraindications Any prior ICH Known structural cerebral vascular lesion (AVM) Known malignant intracranial neoplasm (primary/metastatic) Ischemic stroke within 3 months Suspected aortic dissection Active bleeding or bleeding diathesis (excluding menses) Closed head or facial trauma within 3 months

Thrombolytic Therapy and Mortality According to Admission ECG Lancet 1994;343:311-322 60 49% 50 40 37% 30 Lives Saved per Thousand 20 8% 10 -14% Anterior ST Elevation Inferior ST Elevation BBB -10 ST Depression Admission ECG

ST Elevation Criteria for STEMI ≥1 mm any 2 adjacent standard leads In V2 and V3: Males <40 years of age ≥2.5 mm for males ≥40 years of age ≥2.0 mm for males Females (any age) ≥1.5 mm ST elevation is measured at the J point JACC 2009;53:982-991

Fibrinolytic Agents Fibrin-specific Non-fibrin-specific Patency Rate 90 min TIMI 2 or 3 Tenecteplase (TNK-tPA) 85% Reteplase (rPA) 84% Alteplase (tPA) 73-84% Non-fibrin-specific Streptokinase 60-68% (No longer marketed in the US) JACC 2013;61e78-140

ST Elevation MI Thrombolytic Therapy Primary PCI Chest Pain ASA Chest Pain NTG ECG within 10 minutes ST Elevation NTG Self-Transport: Door to Needle <30 mins Self-Transport: Door to Balloon ≤90 mins NTG EMS Transport: <30 mins NTG EMS transport: ≤90 mins Thrombolytic Therapy Primary PCI

AMI: Post PCI

ST Segment Elevation Admission Post PCI

STEMI PCI: National CV Data Registry In hospital mortality of 43,801 patients with STEMI undergoing PCI: JACC 2009;54:2205-2241 P <0.001 10 8.4% 7.0% 5.6% Mortality 5 4.3% 3% 3.5% 30 mins 60 mins 90 mins 120 mins 150 mins 180 mins Delay in Reperfusion in Minutes

Primary PCI vs IV Thrombolytic Therapy for Acute MI: Review of 23 Randomized Trials 23 randomized clinical trials with 7739 patients with STEMI Thrombolytic therapy = 3867 Primary PCI = 3872 Results: Primary PCI was better than thrombolytic therapy at reducing short-term and long-term death, non-fatal reinfarction, stroke and combined endpoint of death, non-fatal reinfarction and stroke Conclusion: Primary PCI is more effective than thrombolytic therapy for the treatment of STEMI Lancet 2003;361:13-20

PCI Vs Thrombolytic Therapy: Short Term Outcomes 25 P<0.0001 PCI 20 Thrombolytic Therapy P<0.0001 15 Frequency (%) P=0.0002 10 P=0.0003 P<0.0001 5 P=0.0004 Death Death, non-fatal re-infarction or stroke Death Excluding SHOCK data Non-fatal MI Recurrent Ischemia Total Stroke Lancet 2003;361:13-20

PCI Vs Thrombolytic Therapy: Long Term Outcomes 50 P<0.0001 PTCA 40 Thrombolytic Therapy P<0.0001 30 Frequency (%) P=0.0019 20 P<0.0001 P=0.0053 Data Not Available 10 * * Death, non-fatal re-infarction or stroke Death Death Excluding SHOCK data Non-fatal MI Recurrent Ischemia Total Stroke Lancet 2003;361:13-20

Options for Transport of Patients With STEMI and Initial Reperfusion Treatment Hospital fibrinolysis: Door-to-Needle within 30 min. Not PCI capable Call 9-1-1 Call fast EMS on-scene Encourage 12-lead ECGs. Consider prehospital fibrinolytic if capable and EMS-to-needle within 30 min. Inter-Hospital Transfer Onset of symptoms of STEMI 9-1-1 EMS Dispatch EMS Triage Plan PCI capable GOALS 5 min. 8 min. EMS Transport Patient EMS Prehospital fibrinolysis EMS-to-needle within 30 min. EMS transport EMS-to-balloon within 90 min. Patient self-transport Hospital door-to-balloon within 90 min. Dispatch 1 min. Golden Hour = first 60 min. Total ischemic time: within 120 min. Antman EM, et al. J Am Coll Cardiol 2008. Published ahead of print on December 10, 2007. Available at http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001.

Coronary Angioplasty VS Fibrinolytic Therapy in Acute Myocardial Infarction Fibrinolysis Door-to-Needle or FMC to Needle < 30 mins Not PCI capable EMS Transport PCI capable PCI Door-to-Balloon or FMC to Balloon ≤ 90 mins

Coronary Angioplasty VS Fibrinolytic Therapy in Acute Myocardial Infarction 2004 STEMI Guideline DIDO PCI Door-to-Balloon or FMC to Balloon ≤ 90 mins 30 mins Not PCI capable EMS Transport 2013 STEMI Guideline PCI Door-to-Balloon or FMC to Balloon ≤ 90 mins PCI capable PCI Door-to-Balloon or FMC to Balloon ≤ 120 mins

Mortality and Ejection Fraction 50 < 20% N = 799 Mean EF = 46% 40 30 One Year Cardiac Mortality (%) 20 20-39% 10 40-59% > 60% 10 20 30 40 50 60 70 80 Radionuclide Ejection Fraction (%)

STEMI: Standard Therapy Thrombolytic Agent or PCI Aspirin Heparin Clopidogrel Beta Blockers within 24 hours ACE Inhibitors or ARB’s within 24 hours Aldosterone antagonists for EF ≤40% Statins before hospital discharge