1 ACS and Stroke in the Rural Emergency SettingJason McElyea, D.O.

2 My Goal To make you comfortable setting in action a plan of attack for management of the Acute MI or Stroke in a Rural ER/Hospital setting.

3 Objectives Criteria of STEMI/NSTEMI /StrokeKnow the signs of a High Risk STEMI Early invasive vs Conservative therapy Acute medication management Utilizing your resources (TREC) Geared towards the small town doc also covering in the ER

4 Not Covered Typical vs Atypical ACS (appendix B)Differential diagnosis of chest pain (Appendix c) Differential diagnosis of altered sensorium Not bleeding edge Cardiology, follows recent text guidelines

5 Pearls Cardiac risk factors are poor predictors of risk for AMI or ACS, they look at the long term not the immediate.[2] Know what makes the 99th percentile for your area. You want 3 standard deviations from the median. Typically this is 3-5x the upper limit of normal.[3] A reflex cardiac evaluation based solely on an elevated cardiac biomarker without considering whether the episode is indeed consistent with an ACS is inappropriate and may be harmful. [6]

6 Pearls PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) study, mortality at 30 days was 5.1% in patients with ST-segment depression versus 2.1% among those without ST-segment depression [8] O2,nitro,beta blocker, ccb, cholesterol management are level I reccomendation, morphine is a class IIb and then only if you have got them on the maximum amount of anti-ischemic meds.[232,233] Routing use of oxygen in patients with an O2>90% may be associated with increased mortlity [212,213]

7 Pearls Effient has better outcomes than plavix but much greater risk of bleed so avoid in those older than 75 and less than 60kg (TRITON-TIMI) 38 trial [89] You can utilize Trauma TREC for referral to appropriate cardiac/stroke center.

8

9 Overly Simplified

10 European Society of Cardiologists/American College of Cardiology Definition of Myocardial Infarction 2007 [37] Cardiac markers above the 99th percentile of the upper reference limit (URL) and Symptoms of ischemia ECG changes indicative of new ischemia (new ST/T wave changes or new LBBB) Development of new pathologic Q waves on ECG Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality

11 Enzymes and Timing C-reactive protein,serum amyloid A, and interleukin-6 in patients with unstable angina.31-33 not valid for diagnosing myonecrosis at this time. E-selectin and intercellular adhesion molecule-1, are under investigation.34  fibrinopeptide and fibrinogen levels, appear to signify an increased risk of death in ACS patients.35,36 Clinically, none of these markers are currently accepted as a biochemical means of demonstrating myocardial infarction.

12 Enzyme onset [5]

13 Enzyme Sensitivity [5]

14 Elevated Troponin at Baseline

15 Causes of Troponin Elevation other than ACS (c4-perms) [6]Pulmonary embolus Myocarditis Cardiac contusion Congestive heart failure Chemotherapy (Adriamycin, 5-fluorouracil) Cardioversion or radiofrequency ablation Septic shock Extreme endurance athletics Renal failure

16 possible discuss q waves Types of stmiHurst says 2mm in precordials and 1mm In limb leads before tpa

17 Chest pain Establish your safety net EKG within 10 minutes no STEMITele, IV’s, bp, o2 (if<90), labs, aspirin EKG within 10 minutes no STEMI Nitro to effect Beta blocker if tolerable Trop> 3 times the upper limit of normal DX NSTEMI Risk Stratify: High,Med,Low Appendix A ,TIMI,HEART

18 So Step 1

19 Causes of NSTEMI Incomplete occlusionDynamic obstruction (Prinzmetals) Progressive mechanical obstruction (restenosis) Coronary dissection or vasculitis

20 NSTEMI tx Reduce risk of worsening Reduce risk of recurrent IschemiaASA 160 or 325mg [9][75] Clopidogrel (plavix) or Prasugrel (effient) Antithrombin Reduce risk of recurrent Ischemia Beta blockers Nitrates Statin Ccb (to a lesser extent) Selected high risk may benefit from GPIIb/IIIa

21 Clopidogrel (Plavix) dosingCURRENT/OASIS 7 trial showed a loading dose of 600mg before PCI had a 15% reduction in primary end point and 29% reduction in stent thrombosis Significant increase in bleeding in those not getting PCI so recommends 300mg dose

22 Prasugrel (Effient) 60mg loading dose then 10mg per dayHigher risk of bleeding  Ideal candidates for more intensive platelet inhibition include patients (1) not pretreated with "upstream" clopidogrel, (2) at high risk for recurrent nonfatal ischemic events, and (3) not at high bleeding risk. *diabetics not at high risk for bleed not pretreated with clopidogrel may benefit per a subset of data from triton-timi 38 [90]

23 Ticagrelor (Brilinta)180 mg loading then 90mg BID [91] Activity within 30 minutes and full activity at 2 hours CURRENT/OASIS 7 showed benefit over plavix Much less surgical/bleeding complications because of shorter half life[91] *higher rate of side effects: dyspnea and ventricular pauses

24 Anticoagulant therapyAnticoagulants available for parenteral use include UFH, various LMWHs, synthetic pentasaccharides, direct-acting antithrombins hirudin and bivalirudin;

25 Unfractionated Heparin (UFH)Several trials have compared UFH with placebo and form the basis of the class I recommendation for use of UFH with ASA for patients with UA/NSTEMI.1 In a meta-analysis of six trials with end point assessment varying from 2 to 12 weeks, death or MI was reduced by 33% in UFH-treated patients (P = .06).98

26 UFH Initial bolus of 60-70 units/kg with a max bolus of 5000 [8]This is different from epocrates that says 60u/kg max 4000 Then units/kg/hr up to a max of 1000 units per hour[8] Guideline committees recommend dosage adjustments of the nomograms to correspond to a therapeutic range equivalent to heparin levels of 0.3 to 0.7 U/mL by antifactor Xa determinations, which correlates with aPTT values between 60 and 80 seconds. [8]

27 LMWH Enoxiparin (Lovenox) 1mg/kg BID [8]Maxes out at 150mg ESSENCE and TIMI 11B  trials found benefit from enoxaparin compared with UFH in patients with UA/NSTEMI.[99][100] Initial conservative strategy, enoxaparin 28% reduction in the primary composite end point. [102] Harder to reverse for surgery Renal clearance adjuste if GFR<30

28 Fondaparinux (arixtra)2.5mg/day in studies Hard to find a recommended dose Lacks reversibility, associated with catheter thrombus.

29 Direct thrombin inhibitorsHirudin (lepirudin) only approved for patients with HIT Bivalirudin (angiomax) studies support bivalirudin as a safe alternative to UFH or enoxaparinduring PCI, provided patients have been pretreated with a P2Y12 inhibitor. However, because of the high cost of the drug when given as an infusion for 12 to 48 hours and the absence of benefit seen in ISAR-REACT 3, widespread use of this agent does not appear warranted at this time. [8]

30 Glycoprotein IIb/IIIa Inhibitors Two broad strategies characterize current use of these agents in ACS. The first is an "upstream" strategy in which either eptifibatide (integrillin) or tirofiban (aggrastat) is administered in the ED or hospital for medical stabilization, usually in anticipation of an early invasive approach to PCI. The second strategy defers upstream use of these agents and uses either eptifibatide (integrillin) or abciximab (reopro) as adjunctive therapy immediately before PCI.

31 That Being Said Findings suggest that an appropriate strategy is to defer GP Iib/IIIa use until the decision to perform PCI has been made and to use them selectively among high-risk patients defined clinically or angiographically.[8] *Let the cardiologist decide

32 Fibrinolysis in UA/NSTEMIFibrinolytic agents in UA/NSTEMI have had no significant beneficial effect and actually increased the risk of MI in TIMI IIIB.60

33 Chest pain Establish your safety net EKG within 10 minutes no STEMITele, IV’s, bp, o2 (if<90), labs, aspirin EKG within 10 minutes no STEMI Nitro to effect Beta blocker if tolerable Trop> 3 times the upper limit of normal DX NSTEMI Risk stratify:High,Med,Low

34 ACA/AHA Class I for Early Invasive The High Risk patientRecurrent angina/ischemia at rest or with low-level activities despite intensive anti-ischemic therapy Elevated TnT or TnI New or presumably new ST-segment depression Recurrent angina/ischemia with CHF symptoms, an S3 gallop, pulmonary edema, worsening rales, or new or worsening MR High-risk findings on noninvasive stress testing Depressed LV systolic function (eg, EF <0.40 on noninvasive study) Hemodynamic instability Sustained ventricular tachycardia PCI within 6 mo Prior CABG See the appendix for more

35 High Risk Consult cardiologist and initiate transferTo discuss: Cath Plans? Antiplatelet: choose Plavix 300 for later cath or 600 for now (good studies) Brilinta 180mg (less bleeding risk) Effient 60mg Anticoagulants: choose Heparin bolus of units/kg with a max bolus of 5000 , followed by 12u/kg/hr max 1000u/hr Lovenox 1mg/kg SC max dose Do you want GPIIb/IIIa?

36 How Early TIMACS [70] and GRACE[72] showed no difference in early (24 hours) vs delayed (36 hours) in low to moderate risk However urgent (not immediate) has an improvement on all cause mortality and reduced recurrent ischemia [8]

37 Low/Moderate Risk Fasting Lipids [8] Antiplatelet: choosePlavix 300 (good studies), 150mg x7 days, then 75mg /day [8] Brilinta 180mg (less bleeding risk) then 90mg /day Effient 60mg then 10mg per day Anticoagulants: choose Heparin bolus of units/kg with a max bolus of 5000 , followed by 12u/kg/hr max 1000u/hr Lovenox 1mg/kg SC max dose

38 Low to Moderate Risk Risk factor modification:Hypertension, smoking, hyperlipidemia, diabetes [8] As not contraindicated: ASA, plavix, beta blocker, statin, ace-I ( especially if EF <40%) Outpatient or Inpatient stress test.[9] Consider prn nitro,calcium antagonist, ranolazine *If at any point in time patient worsens, re-evaluate

39 Low to Moderate Risk that are acceptable for your facilityLow-risk patients who complete a stay in a chest pain unit without objective evidence of myocardial ischemia can safely undergo stress testing for diagnosis and prognostic purposes either immediately or as an outpatient within the next 72 hours. [9] See alsoAppendix D-so it wasn’t a stemi/nstemi

40 To Cath revisited Thus, in high-risk patients, a routine invasive strategy is generally preferred if there are no contraindications to coronary angiography and if the patient is a good candidate for prolonged clopidogrel therapy.[9] Intermediate-risk patients, the benefits of an invasive approach are attenuated but still present; among Low-risk patients, no benefit exists for the routine invasive approach [3]

41 History of STEMI Complete occlusion results in total cessation of coronary blood flow. Typically new Q waves evolve because of full or nearly full thickness necrosis of the ventricular wall. Q waves only occurs in 70% of patients Therefore the nomenclature has moved from Q-wave MI to STEMI [37][38]

42 STEMI guidelines, the key to documentationH&P 12 lead EKG within 10 minutes. If initial is negative and story is good repeat in 5-10 minutes[12] In inferior infarcts perform a Right sided EKG to look for RV infarction[24]

43 STEMI on EKG with LBBB 1) ST-segment elevation ≥1 mm concordant with the QRS complex; (2) ST-segment depression ≥1 mm in leads V1, V2, or V3; and (3) ST-segment elevation ≥5 mm discordant with the QRS [11]

44 EKG Limitation (1) Even though ST-segment elevation usually signifies acute coronary occlusion, acute coronary occlusion may not cause ST-segment elevation in certain circumstances, such as a circumflex artery occlusion; (2) in addition, not all ST-segment elevation is caused by AMI; and (3) finally, an old LBBB limits the usefulness of the ECG for AMI diagnosis in this subset of patients.

45 STEMI Criteria A history suggestive of coronary ischemia for a prolonged period of time (>30 minutes), Evolutionary changes on serial ECGs suggestive of myocardial infarction A rise and fall in serum cardiac markers consistent with myonecrosis. 

46 Slide on EKG findings Picutres, definition

47 CP

48

49

50 To Consider How long does it take transport?Initiate a local Code STEMI 5 minutes Call ambulance 5 minutes Ambulance loads up 10 minutes I supervise a small town EMS, these numbers are hopeful. Have a plan and a location ahead of time Don’t know the nearest place with PCI capabilities, call Trauma TReC TIME IS MUSCLE

51 Recent randomized data suggest that all STEMI patients who are treated with fibrinolytic therapy benefit from routine coronary angiography during the index hospitalization.[68]

52 Adjuvant antiplatelet therapy

53 Plavix with fibrinolysisCurrent data suggest that a 300-mg loading dose before fibrinolysis followed by 75 mg daily of clopidogrel is beneficial and safe.

54 Plavix w/ PCI The effectiveness of clopidogrel in the setting of primary PCI for STEMI is unproven, but extrapolation of the data indicating that upstream clopidogrel dosing improves PCI outcomes in non–ST-segment elevation myocardial infarction and scheduled PCI has led to the recent reasonable recommendation for oral clopidogrel loading at STEMI presentation and long-term maintenance therapy, barring contraindications in those younger than age 75 [71]

55 Prasugrel (Effient) A boxed warning regarding bleeding risk emphasizes that prasugrel is not recommended for those with a history of transient ischemic attack or stroke, patients over age 75 years, or patients who are likely to undergo coronary artery bypass grafting within the ensuing 7 days. [73]

56 Clinical guidelines for thienopyridines [27][33]A)Plavix 300 to 600mg as early as possible or B)Prasugrel 60mg asap for primary PCI

57 For non primary PCI (i)If the patient has received fibrinolytic therapy and has been givenclopidogrel, clopidogrel should be continued as the thienopyridine of choice. (Level of Evidence: C) (ii)If the patient has received fibrinolytic therapy without a thienopyridine, a loading dose of 300 to 600 mg of clopidogrel should be given as the thienopyridine of choice. (Level of Evidence: C) (iii) If the patient did not receive fibrinolytic therapy, either a loading dose of 300 to 600 mg of clopidogrel should be given, or once the coronary anatomy is known and PCI is planned, a loading dose of 60 mg of prasugrel should be given promptly and no later than 1 hour after the PCI. (Level of Evidence: B)

58 At this point we have handed off to the Cardiologist.

59 PCI without Onsite Surgical Backup (is it possible) Aversano et al94 conducted the multicenter, prospective, randomized C-PORT (Atlantic Cardiovascular Patient Outcomes Research Team) trial to investigate the feasibility of off-site primary PCI. In this study, 11 centers with cardiac catheterization facilities, but no surgical backup, randomized 451 fibrinolytic therapy–eligible STEMI patients to fibrinolytic therapy or primary PCI at the community hospital. The composite primary end point of death, recurrent myocardial infarction, and stroke at 6 months occurred in 19.9% of those in the fibrinolytic group and 12.4% of those in the PCI group (P = .03).

60 Mayo studies Showed a 93% success rate without any major complications and no patienst requried emergency bypass. The primary endpoints for offsite was the same as onsite [95]

61 guideline Because rescue PCI appears to be the treatment of choice for patients who fail fibrinolytic therapy, all patients who are given fibrinolytics should be immediately transported to a PCI center in case of the need for rescue PCI.[12]

62 So they walk through the door with a stemi[12]What to the y need? 02 if <90 [24] (IIA-C for use in all) ASA 162 or 325 chewed Antiplatelets (clopidogrel or prasugrel) Beta blocker (in first 24 hours) If no failure, low output, heart block, bradycardia NTG x3 then drip if needed (be aware of RV and sytolic <90, PDE-I)

63 More drugs[24,27,33] If plan fibrinolyticHeparin 60mg/kg boluse up to 4000 then 12 u / kg/hr up to 1000u/hr (up to 48 hours) LMWH <75 and gfr >30 30mg IV then 1mg/kg bid (48 hr min, up to 8 days) Fondaparinux: 2.5mg IV then sq daily

64 For patients proceeding to primary PCI who have been treated with aspirin and a thienopyridine, recommended supportive anticoagulant regimens include the following: For prior treatment with UFH, additional boluses of UFH should be administered as needed to maintain therapeutic activated clotting time levels taking into account whether glycoprotein IIa/IIIb receptor antagonists have been administered. (Level of Evidence: C) Bivalirudin may also be used in patients treated previously with UFH. (Level of Evidence: C) For prior treatment with enoxaparin, if the last subcutaneous dose was administered within the prior 8 to 12 hours earlier, an intravenous dose of 0.3 mg/kg of enoxaparinshould be given. (Level of Evidence: B) For prior treatment with fondaparinux, administer additional intravenous treatment with an anticoagulant possessing anit-IIa activity, taking into account whether glycoprotein IIb/IIIa receptor antagonists have been administered. (Level of Evidence: C) Bivalirudin is useful as a supportive measure for primary PCI with or without prior treatment with UFH. (Level of Evidence: B) if heparin allergies

65 Class I Every community should have a written protocol that guides emergency medical services system personnel in determining where to take patients with suspected or confirmed STEMI. (Level of Evidence: C) Hospitals should establish multidisciplinary teams (including primary care physicians, emergency medicine physicians, cardiologists, nurses, and laboratorians) to develop guideline-based, institution-specific written protocols for triaging and managing patients who are seen in the prehospital setting or present to the emergency department with symptoms suggestive of STEMI. (Level of Evidence: B)

66 Glycoprotein IIb/IIIa Inhibitors abciximab, tirofiban, and eptifibatide ASSENT-3, INTEGRITI , Gusto-V state that these should not be used in combination with fibrinolytic therapy.  A meta-analysis of six of these trials by Montalescot et al[88] showed that early administration of glycoprotein IIb/IIIa inhibitors in STEMI patients was associated with a greater prevalence of TIMI flow grade 2 or 3 (41.7% vs 29.8%; P < .001) in the infarct-related artery before PCI. 

67 Contraindications to fibrinolytics

68 Absolute ContraindicationsPrior Intracranial bleed Known structural cerebrl vascular leison Known malignat intracranial neoplasm Ischemic stroke within 3 months except acute ischemic stroke within 3 hours Actrive bleeding or bleeding diathesis Significant closed head trauma or facial trauma within 3 months.

69 Relative ContraindicationsHistory of Chronic , sever, poorly controlled hypertension Severe uncontrolled hypertension (Sbp>180, DBP >110) Traumatic or prolong CPR or major surgery (<3 weeks Recent internal bleeding Noncompressible vascular punctures Pregnancy Active Peptic Ulcer Current Use of anticoagulants( higher risk of bleeding)

70 Stroke [14] Stroke is the fourth leading cause of death in the USThere are ongoing studies to improve the publics awareness of signs and symptoms of a stroke. Pre hospital teams should be using there preferred scale and triaging as appropriate

71 Current Guidelines For patients with suspected stroke , EMS should bypass hospitals that do not have resources to treat stroke and go to the closest facilty most capable of treating acute stroke.

72 Insert Trauma TReC Map

73

74 Emergency evaluaton Move fast, test fast, have a plan in place ahead of time. The goal is to complete the evaluation and begin fibrolytic treatmentwithin 60 minuts of the patients arrival in the ED. NIHSS stroke scale is recognized as a standard Be aware, someone can have a high number at bseline. This number is really just useful for documenting change.

75 So they roll in the door Based on the AHA reccs, we call a code stroke. A team of nurses, lab, CT tech, and house supervisor respond. While we are awaiting arrival of the whole team the nurse starts a line to get cbc, cmp, coags, fsbs, trop A tech is placing leads for ekg As soon as CT is ready for him they go straight down. If ems encodes and it sounds legitmate we go straight to CT

76 Don’t delay Things like CXR that may not be pertinent or waiting for a UA shouldn’t delay decision making process to admin TPA Get them a NONCONTRAST head CT If available MRI is wonderful There are many more imaging studies but this is geared to the rural setting.

77 Insert TPA contraindications

78 Imaging A change from the 2009 guidelines is that regardless of size areas of early ischemic changes should get tpa CTA and MRA may help selected patietns who are beyond IV thrombolytic therapy MRI is the first choice, if not immediately available then CT

79 Principle of care Restore tissue oxygenation,Correct hypoxemia and hypotension Cardiac mointoring for the first 24 hours Get bp to sbp<185 and diastolic <110 before tpa and keep it there for 24 hours after. Keep O2>94% Keep body temp <38C Correct hypoglycemia ( goal)and hypovolemia

80 The consensus is that if a pt is not receiving TPA there blood pressure may run as high as systolic 220 If it is higher you should lower no more than 15% in the first 24 hours Supplemental O2 is not reccomended in non-hypoxic patients.

81 RBA of TPA NINDS rtPA trial, has 1.9 odds ratio of an improved outcome at 1 year 6.4% of patients receiving tpa will have a worsening of symptoms However the mortality is the same as placebo at 3 months

82 Extended IV rtPA windowECASS III results indacted that IV rtPA can improve outcomes for carefully selected patietns hours after stroke A meta analysis show that it can be beneficial at 6 hours but is best within 3 hours. Each facility should have a door to needle to of 60 minutes for 80% of patients.

83 Future points The practice of withholding IV fibrinolytic therapy because of mild or rapdily improving symptoms has been questioned and is being looked in to. In patients known to be on direct thrombin inhibitors (-rudins) of factor Xa (-xaban, xarelto, eliquis), cautious treatment may be pursued. Only if you have the ablity to get an aPTT, ECT, TT, INR, and platelet count

84 Treatment rTPA (.9mg/kg, max 90mg) if within 3 hours.10% as bolus and then remainder over 60minutes Same dose may be used at hours if additional exclusioncriteria >80 yo, on oral anticoags, baseline NIHSS>25, >1/3 MCA territory, or hx of cva and diabetes

85 Contraindications I’ll be honest, most people don’t remember them allGet an app Use Mdcalc. If you do it enough they become second nature.

86 Eligibility >18 years old Diagnosed as stroke<4.5 hours since onset

87 Absolute Contraindications [15]Bleed on CT SBP>185 or DBP >110 History of Intracranial Hemorrhage Seizure at stroke onset ( may be changing) Known av malformation, neoplasm, or aneurysm Active internal bleeding Plt<100, heparin in last 48hrs, inr>1.7 Current direct thrombin inhibitor/ XA inhib Glucose<50 or >400

88 Relative contraindications[15]Minor or rapidly changing (in debate) Major surgery or serious trauma in past 14 days History of GI or urinary hemorrhage within 21 days Recent arterial puncture at noncompressible site. Recent lumbar puncture Post MI pericarditis (dressler syndrome) Pregnancy

89 Alteplase is the only fibrinolytic that has an FDA approval, others should only be used in clinical trials

90 Past the rural setting Intra-arterial fibrionlysisCombination of IA and IV (holding, not likely) Mechanical clot disruption/extraction These are back up plans/advanced options, Don’t alter your plans based on the possiblity of others

91 Early use of UFH or LMWH do not lower the risk of early recurrent stroke, including among persons with cardioembolic sources It increases the risk of bleeding. Do not give within 24 hours of IV rtPA

92 Antiplatelet agents ASA 325 at hours is the only reccomended option, Not within the first 24 hours Research is still ongoing in other drugs. Plavix is still being looked at gpIIb/IIIa not recommended

93 Remember These patients should be re-routed to the nearest stroke center ASAP. Call Trauma trec for your region, they can arrange the transfer and assignment

94 So Really, What Do the Guidelines say?If you are not a stroke center get them to one. While you are waiting correct any underlying disorders you can Hypoglycemia, Hypoxia (if decompensate, intubate) Infection Hypertension SBP>220 Keep them NPO

95 What not to do NO steroids NO anticonvulsants unless actively seizing

96 CAPTIM (Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction)Results indicated that regardless of time of symptom onset, there was no significant difference between prehospital fibrinolysis and primary PCI in the primary end point of combined death, reinfarction, or disabling stroke (7.4% vs 6.5% [P = .855] in those with <2 hours symptom onset and 9.1% vs 5.9% [P = .326] in those with >2 hours symptom onset). 

97 Fibrinolysis is not superior to PCIThe results of CAPTIM are consistent with those of PRAGUE-2, which showed similar mortality rates for fibrinolysis and primary PCI when patients presented within 3 hours of symptom onset, but a higher mortality with fibrinolysis when patients were randomized after 3 hours. Long-term mortality data of CAPTIM were recently published, indicating outcomes consistent with those of the initial study[67]

98 Appendix A [6] High likelihood Known coronary disease (particularly recent PCI)Typical angina reproducing prior documented angina Hemodynamic or ECG changes during pain Dynamic ST-segment elevation or depression of ≥1 mm Marked symmetric T-wave inversion in multiple precordial leads Elevated cardiac enzymes in a rising and falling pattern Intermediate likelihood Absence of high-likelihood features and any of the following:Typical angina in a patient without prior documented angina Atypical anginal symptoms in diabetics or in nondiabetics with two or more other risk factors Male gender Age older than 70 y Extracardiac vascular disease ST depression mm or T-wave inversion of ≥1 mm Low-level troponin elevation that is "flat" and does not rise or fall Low likelihoodAbsence of high- or intermediate-likelihood features but may have:Chest discomfort reproduced by palpationT waves flat or inverted <1 mm Normal ECG

99 Appendix B

100 Timi Score TIMI Risk Score TIMI Score Calculation (1 point for each):Age ≥ 65 Aspirin use in the last 7 days (patient experiences chest pain despite ASA use in past 7 days) At least 2 angina episodes within the last 24hrs ST changes of at least 0.5mm in contiguous leads Elevated serum cardiac biomarkers Known Coronary Artery Disease (CAD) (coronary stenosis ≥ 50%) At least 3 risk factors for CAD, such as: Hypertension -> 140/90 or on anti-hypertensives Current cigarette smoker Low HDL cholesterol (< 40 mg/dL) Diabetes mellitus Family history of premature CAD Male first-degree relative or father younger than 55 Female first-degree relative or mother younger than 65 Score Interpretation: % risk at 14 days of: all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization. Score of 0-1 = 4.7% risk Score of 2 = 8.3% riskScore of 3 = 13.2% risk Score of 4 = 19.9% risk Score of 5 = 26.2% riskScore of 6-7 = at least 40.9% risk

101 Heart Score History Highly suspicious 2, Moderately suspicious 1, Slightly suspicious 0  ECG Significant ST-depression 2,Non specific repolarisation disturbance 1, Normal0  Age≥ 65 years 2, 45 – 65 years1 ,≤ 45 years 0  Risk Factors≥ 3 risk factors or history of atherosclerotic disease 2,1 or 2 risk factors 1,No risk factors known 0  Troponin≥ 3x normal limit 2,1 – 3x normal limit 1≤ ,normal limit0

102 Appendix D-so it wasn’t a stemi/nstemiDischarge From the ED or Chest Pain Unit: Recommendations Class IIa 1. It is reasonable to observe patients with symptoms consistent with ACS without objective evidence of myocardial ischemia (nonischemic initial ECG and normal cardiac troponin) in a chest pain unit or telemetry unit with serial ECGs and cardiac troponin at 3- to 6-hour intervals.196,197,199–201 (Level of Evidence: B) 2. It is reasonable for patients with possible ACS who have normal serial ECGs and cardiac troponins to have a treadmill ECG200–202 (Level of Evidence: A), stress myocardial perfusion imaging,200 or stress echocardiography203,204 before discharge or within 72 hours after discharge. (Level of Evidence: B) 3. In patients with possible ACS and a normal ECG, normal cardiac troponins, and no history of CAD, it is reasonable to initially perform (without serial ECGs and troponins) coronary CT angiography to assess coronary artery anatomy205–207 (Level of Evidence: A) or rest myocardial perfusion imaging with a technetium-99m radiopharmaceutical to exclude myocardial ischemia.208,209 (Level of Evidence: B) 4. It is reasonable to give low-risk patients who are referred for outpatient testing daily aspirin, shortacting nitroglycerin, and other medication if appropriate (eg, beta blockers), with instructions about activity level and clinician follow-up. (Level of Evidence: C)

103 Effient may be better than brilinta[30]

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