Unstable angina/ NSTEMI resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Andrea Tamayo Soto [2]; Rim Halaby, M.D. [3]

Unstable angina/ NSTEMI Resident Survival Guide Microchapters
Overview
Causes
FIRE
Diagnosis
Treatment
Do's
Don'ts

Overview

Unstable angina is an unexpected chest pain that starts on minimal exertion, rest or sleep, lasts at least 20 minutes up to half an hour and is not relieved by medications or rest. Unstable angina and non ST elevation myocardial infarction (NSTEMI) belong to two different ends of the spectrum of acute coronary syndrome. Unstable angina is differentiated from NSTEMI by the absence of elevated cardiac biomarkers.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Unstable angina and NSTEMI are life-threatening conditions and must be treated as such irrespective of the causes.

Common Causes

• Atherosclerosis
• Non-occlusive thrombus

FIRE: Focused Initial Rapid Evaluation

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention.

Boxes in the red color signify that an urgent management is needed.

Identify cardinal findings of Unstable angina/ NSTEMI : ❑ Chest pain or chest discomfort ❑ Sudden onset ❑ Sensation of heaviness, tightness, pressure, or squeezing ❑ Duration> 20 minutes ❑ Radiation to the left arm, jaw, neck, right arm, back or epigastrium ❑ No relief with medications ❑ No relief with rest ❑ Worse with time ❑ Worse with exertion ❑ Associated symptoms of palpitations, nausea, vomiting and sweating ❑ Characteristic ECG changes consistent with unstable angina/ NSTEMI ❑ No changes ❑ Non specific ST / T wave changes ❑ Flipped or inverted T waves ❑ ST depression (carries the poorest prognosis) ❑ Increase in troponin and / or CK MB

Rule out life threatening alternative diagnoses: ❑ Aortic dissection (suggestive findings: back pain, |interscapular pain, aortic regurgitation, pulsus paradoxus, blood pressure discrepancy between the arms) ❑ Pulmonary embolism (suggestive findings: acute onset of dyspnea, tachypnea, hemoptysis, previous DVT) ❑ Cardiac tamponade (suggestive findings: hypotension, jugular venous distention, muffled heart sounds, pulsus paradoxus) ❑ Tension pneumothorax (suggestive findings: sudden dyspnea, tachycardia, chest trauma, unilateral absence of breath sound) ❑ Esophageal rupture (suggestive findings: vomiting, subcutaneous emphysema)

Begin initial treatment: ❑ Administer 162 - 325 mg of non enteric aspirin ❑ Orally, crushed or chewed, OR ❑ Intravenously ❑ Administer 2-4 L/min oxygen via nasal cannula when saturation <90% ❑ Caution in COPD patients: maintain an oxygen saturation between 88% and 92% ❑ Administer beta-blockers (unless contraindicated) and titrate to the heart rate and blood pressure Contraindicated in heart failure , prolonged or high degree AV block , reactive airway disease , high risk of cardiogenic shock and low cardiac output state ❑ Metoprolol IV, 5 mg every 5 min, up to 3 doses ❑ Carvedilol IV, 25 mg, two times a day ❑ Administer sublingual nitroglycerin 0.4 mg every 5 minutes for a total of 3 doses Contraindicated in suspected right ventricular MI , recent use of phosphodiesterase inhibitors , decreased blood pressure 30 mmHg below baseline ❑ Administer IV morphine if needed ❑ Initial dose 4-8 mg ❑ 2-8 mg every 5 to 15 minutes, as needed ❑ Administer 80 mg atorvastatin ❑ Monitor with a 12-lead ECG all the time

Does the patient have any of the following indications that require immediate angiography and revascularization ? ❑ Hemodynamic instability or cardiogenic shock ❑ Severe left ventricular dysfunction or heart failure ❑ Recurrent or persistent rest angina despite intensive medical therapy ❑ New or worsening mitral regurgitation or new VSD ❑ Sustained VT or VF ❑ Prior PCI within past 6 months or CABG

YES

NO

Proceed to angiography

Low risk Initial conservative strategy

High risk Initial invasive strategy

Administer ONE of the following antiplatelet agents (before or at the time of PCI): ❑ P2Y12 receptor inhibitors ❑ Clopidogrel 600 mg ❑ Ticagrelor 180 mg ❑ Prasugrel 60 mg Prasugrel is contraindicated in case of prior history of strokes or TIAs, active pathological bleeding, age ≥75 years, when urgent coronary artery bypass graft surgery (CABG) is likely, body weight <60 kg, propensity to bleed, concomitant use of medications that increase the risk of bleeding ❑ IV GP IIb/IIIa inhibitors ❑ Abciximab ❑ Loading dose 0.25 mg/kg IV bolus ❑ Maintenance dose 0.125 mg/kg/min ❑ Eptifibatide ❑ Loading dose 180 mcg/kg IV bolus ❑ Another 180 mcg/kg IV bolus after 10 minutes ❑ Maintenance dose 2 mcg/kg/min ❑ Decrease infusion by 50% if creatinine clearance <50 mL/min ❑ Avoid in hemodialysis patients ❑ Tirofiban ❑ Loading dose 25 mcg/kg ❑ Maintenance dose 0.15 mcg/kg/min ❑ Decrease infusion by 50% if creatinine clearance <30 mL/min Administer ONE of the following anticoagulant therapy: ❑ Unfractionated heparin ♦ If GP IIb/IIIa receptor antagonist is planned ❑ 50- to 70-U/kg IV bolus ♦ If no GP IIb/IIIa receptor antagonist is planned ❑ 70- to 100-U/kg bolus ❑ Bivalirudin ❑ 0.75-mg/kg IV bolus, then 1.75–mg/kg/h infusion ❑ Additional bolus of 0.3 mg/kg if needed ❑ Decrease infusion to 1 mg/kg/h when creatinine clearance <30 mL/min

Administer one of the following antiplatelet agents: ❑ Clopidogrel ❑ Loading dose (300 mg) ❑ Maintenance dose for up to 12 months (75 mg) ❑ Ticagrelor ❑ Loading dose (180 mg) ❑ Maintenance dose for up to 12 months (90 mg twice daily)

Administer one of the following antiplatelet agents: Before PCI ❑ P2Y12 receptor inhibitors ❑ Clopidogrel (600 mg), or ❑ Ticagrelor (180 mg), or ❑ IV GP IIb/IIIa inhibitors ❑ Eptifibatide ❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes ❑ Maintenance dose 2 mcg/kg/min, or ❑ Tirofiban ❑ Loading dose 25 mcg/kg ❑ Maintenance dose 0.15 mcg/kg/min At the time of PCI ❑ P2Y12 receptor inhibitors ❑ Clopidogrel (600 mg), or ❑ Ticagrelor (180 mg), or ❑ Prasugrel (60 mg) ❑ IV GP IIb/IIIa inhibitors ❑ Eptifibatide ❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes ❑ Maintenance dose 2 mcg/kg/min, or ❑ Tirofiban ❑ Loading dose 25 mcg/kg ❑ Maintenance dose 0.15 mcg/kg/min

Consider urgent CABG if the coronary anatomy is not amenable to PCI and one of the following: ❑ Patients with left main or left main equivalent disease ❑ Patients with three or two vessel disease involving the left anterior descending artery with left ventricular dysfunction ❑ Diabetic patients

Continue with the complete diagnostic approach below

❑ Perform an angiography

Complete Diagnostic Approach

A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.

Abbreviations: CABG: coronary artery bypass graft; ECG: electrocardiogram; LAD: left anterior descending; LBBB: left bundle branch block; MI: myocardial infarction; PCI: percutaneous coronary intervention; S3: third heart sound; S4: fourth heart sound; VSD: ventricular septal defect

Characterize the symptoms: ❑ Chest pain or chest discomfort ❑ Sudden onset ❑ Sensation of heaviness, tightness, pressure, or squeezing ❑ Duration> 20 minutes ❑ Radiation to the left arm, jaw, neck, right arm, back or epigastrium ❑ No relief with rest ❑ Worse with time ❑ Worse with exertion ❑ Dyspnea ❑ Weakness ❑ Palpitations ❑ Nausea ❑ Vomiting ❑ Sweating ❑ Loss of consciousness ❑ Fatigue
Obtain a detailed history: ❑ Age ❑ Baseline blood pressure ❑ Previous episodes of chest pain ❑ Previous PCI or CABG ❑ Cardiac risk factors ❑ Hypertension ❑ Diabetes ❑ Hypercholesterolemia ❑ Smoking ❑ Obesity ❑ List of medications ❑ Family history of premature coronary artery disease Identify possible triggers: ❑ Physical exertion ❑ Air pollution or fine particulate matter ❑ Antecedant infection ❑ Heavy meal ❑ Cocaine ❑ Marijuana
Examine the patient: Vital signs ❑ Blood pressure ❑ Blood pressure lower than baseline, suggestive of: ❑ Discrepancy between arms (suggestive of aortic dissection) ❑ Narrow pulse pressure (suggestive of heart failure) ❑ Heart rate ❑ Tachycardia (suggestive of heart failure) ❑ Bradycardia (suggestive of heart block or bradyarrhythmias) Pulses ❑ Femoral pulse (if a patient is to undergo PCI) ❑ Strength ❑ Bruits Skin ❑ Xanthelasma (suggestive of dyslipidemia) ❑ Xanthoma (suggestive of dyslipidemia) ❑ Edema (suggestive of heart failure) ❑ Cyanotic and cold skin, lips, nail bed (suggestive of cardiogenic shock) Heart ❑ Heart sounds ❑ S3 (suggestive of heart failure) ❑ S4 (associated with conditions that increase the stiffness of the ventricle) ❑ Murmurs ❑ Aortic regurgitation: early diastolic high-pitched sound best heard at the left sternal border (suggestive of aortic dissection with propagation to the aortic arch) ❑ Pericardial friction rub (suggestive of pericarditis) Lungs ❑ Rales (suggestive of heart failure)
Order labs and tests: ❑ EKG ❑ Biomarkers ❑ Troponin I ❑ CK-MB ❑ Echocardiography ❑ Creatinine ❑ Glucose ❑ Hemoglobin ❑ Multislice CT coronary imaging (rule out CAD as cause of pain in patients with low to intermediate likelihood of CAD and when troponin and ECG are inconclusive) ❑ MRI (integrate imaging of function, perfusion and necrosis)

Treatment

Shown below is an algorithm summarizing the management of unstable angina and NSTEMI based on the 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction.

Initial Treatment ❑ Administer 162 - 325 mg of aspirin ❑ Administer oxygen when saturation <90% ❑ 2-4 L/min via nasal cannula ❑ Administer beta-blockers (unless contraindicated) ❑ Metoprolol IV, 5 mg every 5 min, up to 3 doses ❑ Carvedilol IV, 6,25 mg, two times a day (titrate to heart rate) ❑ Administer sublingual nitroglycerin 0.4 mg every 5 minutes for a total of 3 doses ❑ Administer IV morphine if needed ❑ Initial dose 2-4 mg ❑ 2-8 mg every 5 to 15 minutes, as needed ❑ Administer 80 mg atorvastatin ❑ Administer antithrombotic treatment ❑ Fondaparinux, or ❑ UFH in case of renal failure ❑ Monitor with a 12-lead EKG all the time

Determine the risk of adverse coronary event: ❑TIMI Score, or ❑HEART Risk Score, or ❑GRACE Risk Score

Low risk Initial conservative strategy

High risk Initial invasive strategy

Administer one of the following antiplatelet agents: ❑ Clopidogrel ❑ Loading dose (300 mg) ❑ Maintenance dose for up to 12 months (75 mg) ❑ Ticagrelor ❑ Loading dose (180 mg) ❑ Maintenance dose for up to 12 months (90 mg twice daily)

Administer one of the following antiplatelet agents: Before PCI ❑ P2Y12 receptor inhibitors ❑ Clopidogrel (600 mg), or ❑ Ticagrelor (180 mg), or ❑ IV GP IIb/IIIa inhibitors ❑ Eptifibatide ❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes ❑ Maintenance dose 2 mcg/kg/min, or ❑ Tirofiban ❑ Loading dose 25 mcg/kg ❑ Maintenance dose 0.15 mcg/kg/min At the time of PCI ❑ P2Y12 receptor inhibitors ❑ Clopidogrel (600 mg), or ❑ Ticagrelor (180 mg), or ❑ Prasugrel (60 mg) ❑ IV GP IIb/IIIa inhibitors ❑ Eptifibatide ❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes ❑ Maintenance dose 2 mcg/kg/min, or ❑ Tirofiban ❑ Loading dose 25 mcg/kg ❑ Maintenance dose 0.15 mcg/kg/min

Recurrent or worsening symptoms?

❑ Perform an angiography

❑ Recurrence of symptoms ❑ Heart failure ❑ Serious arrhythmia ❑ Subsequent ischemia

No recurrent symptoms

❑ Perform an angiography Administer upstream antiplatelet agent: ❑ P2Y12 receptor inhibitors ❑ Clopidogrel ❑ Loading dose (600 mg) ❑ Maintenance dose (75 mg), or ❑ Ticagrelor ❑ Loading dose (180 mg) ❑ Maintenance dose (90 mg twice daily), or ❑ IV GP IIb/IIIa inhibitors ❑ Eptifibatide ❑ Loading dose 180 mcg/kg IV bolus followed by another bolus after 10 minutes ❑ Maintenance dose 2 mcg/kg/min, or ❑ Tirofiban ❑ Loading dose 25 mcg/kg ❑ Maintenance dose 0.15 mcg/kg/min

❑ Perform a stress test

Low Risk

High Risk

❑ Perform an angiography

❑ Continue aspirin for life ❑ Continue P2Y12 receptor inhibitors up to 12 months ❑ Clopidogrel (75 mg once a day), or ❑ Ticagrelor (90 mg twice a day) ❑ Discontinue GP IIb/IIIa inhibitors ❑ Continue antithrombotic therapy: ❑ UFH for 48 hours, or ❑ Enoxaparin for up to 8 days, or ❑ Fondaparinux for up to 8 days

Management Following Angiography

Does the angiography show coronary vessel obstruction ?

No

Yes

❑ 1 or 2 vessel disease CABG or medical therapy might also be considered

❑ Left main coronary artery disease ❑ 3 vessel disease ❑ 2 vessel disease with proximal left anterior descending artery affection ❑ Left ventricular dysfunction ❑Patient treated from diabetes

Medical treatment

PCI

CABG

❑ Continue aspirin ❑ Administer a loading dose of P2Y12 receptor inhibitors (if not given before angiography) ❑ Clopidogrel (600 mg), or ❑ Prasugrel (60 mg) ❑ Discontinue IV GP IIb/IIIa inhibitors if started ❑ Manage antithrombotic therapy if given before angiography: ❑ Continue IV UFH for 48 hours or until discharge ❑ Continue enoxaparin for entire hospital stay, up to 8 days ❑ Continue fondaparinux for entire hospital stay, up to 8 days ❑ Discontinue bivalirudin or continue, 0.25 mg/kg/hour for up to 72 hours

❑ Administer aspirin for life ❑ Administer a loading dose of P2Y12 receptor inhibitor (if not initially started) ❑ Clopidogrel 600 mg ❑ Ticagrelor 180 mg ❑ Prasugrel 60 mg ❑ Discontinue anticoagulant in uncomplicated cases

❑ Continue aspirin ❑ Discontinue IV GP IIb/IIIa inhibitors (4 hours before CABG) ❑ Manage the P2Y12 receptor inhibitor therapy (if CABG can be delayed) ❑ Discontinue clopidogrel (5 days prior to CABG) ❑ Discontinue ticagrelor (5 days prior to CABG) ❑ Discontinue prasugrel (7 days prior to CABG) ❑ Manage the antithrombotic therapy ❑ Continue UFH ❑ Discontinue enoxaparin (12-24 hours prior to CABG) ❑ Discontinue fondaparinux (24 hours prior to CABG) ❑ Discontinue bivalirudin (3 hours prior to CABG)

Pre-Discharge Care

Abbreviations: ACE: angiotensin converting enzyme; LVEF: left ventricular ejection fraction; PCI: percutaneous coronary intervention; PO: per os; VF: ventricular fibrillation; VT: ventricular tachycardia

Administer the following medications in patients without contraindications: ❑ Aspirin 81-325 mg (indefinitely) ❑ Beta blockers Contraindicated in heart failure, prolonged or high degree AV block, reactive airway disease, high risk of cardiogenic shock and low cardiac output state ❑ Metoprolol tartrate ❑ Begin with 25 to 50 mg PO every 6 to 12 hour ❑ Then, metoprolol tartrate twice daily or metoprolol succinate once daily for 2-3 days ❑ Titate to 200 mg daily, OR ❑ Carvedilol ❑ Begin with 6.25 mg twice daily ❑ Titrate to 25 mg twice daily ❑ Calcium channel blockers are used as anti-ischemic or antihypertensive drugs and also in atrial fibrillation when beta blockers are contraindicated Contraindicated in heart failure and left ventricular dysfunction ❑ ACE inhibitors and ARBs may also be considered in the management Contraindicated in hypotension, renal failure and hyperkalemia ❑ Atorvastatin 80 mg daily Administer antiplatelet therapy For patients who underwent PCI, for one year ❑ Clopidogrel 75 mg daily, OR ❑ Prasugrel 10 mg daily, OR ❑ Ticagrelor 90 mg twice a day Assess the patient for ischemia: ❑ Perform non invasive testing before discharge for the evaluation of ischemia among patients who did not undergo coronary angiography and in whom coronary angiography is not warranted due to the absence of high risk features (Class I, level of evidence B) ❑ Assess the LVEF (Class I, level of evidence C)

Long Term Management

Abbreviations: ACE: angiotensin converting enzyme; ARB: angiotensin receptor blocker;

❑ Prepare a list of all the home medications and educate the patient about compliance ❑ Aspirin 81-325 mg (indefinitely) ❑ Antiplatelet therapy ❑ Beta blockers ❑ ACE inhibitors or ARB ❑ Atorvastatin 80 mg daily ❑ Encourage lifestyle modification ❑ Smoking cessation ❑ Physical activity ❑ Dietary changes ❑ Ensure the initiation of the management of comorbidities ❑ Obesity ❑ Dyslipidemia ❑ Hypertension ❑ Diabetes ❑ Heart failure ❑ Educate the patient about the early recognition of symptoms of acute coronary syndrome ❑ Educate the patient about the use of nitroglycerin 0.4 mg, sublingually, up to 3 doses every 5 minutes

Thrombolysis in Myocardial Infarction (TIMI) Risk Score

Shown below is a table summarizing the TIMI scoring system. The risk of subsequent death, myocardial Infarction or need for revascularization within two weeks from the initial presentation is 4.7%, 8.3%, 13.2%, 19.9%, 26.2%, 40.9% for risk scores of 0-1, 2, 3, 4, 5, 6 and 7 respectively.

Criteria	Score
Adults 65 years and older	1
Previous coronary artery stenosis > 50% Cardiac catherterization Angioplasty or stent Bypass Myocardial infraction	1
Cardiac risk factors (three or more) Hypertension Diabetes High cholesterol MI in family history Tobacco history	1
Use of aspirin the previous week	1
Anginal events (two or more) in the previous day	1
ST segment alteration (>1mm elevation or depression)	1
Cardio bio-markers elevated	1

HEART Risk Score

Factors	Degree	Score
History	Highly suspicious Moderately suspicious Slightly suspicious	2 1 0
EGC	Significant ST depression Non-specific repolarisation disturbance Normal	2 1 0
Age	>65 years 45-65 years <45 years	2 1 0
Risk Factors	> 3 risk factors or history of atherosclerotic disease 1 or 2 risk factors No risk factors	2 1 0
Troponin	>3x the normal limit 1-3x the normal limit < the normal limit	2 1 0
		TOTAL

GRACE Risk Score

Factor	Categories	Score
Age (years)	<40 40-49 50-59 60-69 70-79 >80	0 18 36 55 73 91
Heart Rate (bpm)	<70 70-89 90-109 110-149 150-199 >200	0 7 13 23 36 46
Systolic Blood Pressure (mmHg)	<80 80-99 100-119 120-139 140-159 160-199 >200	63 58 47 37 26 11 0
Creatinine (mg/dL)	0-0.39 0.4-0.79 0.8-1.19 1.2-1.59 1.6-1.99 2-3.99 >4	2 5 8 11 14 23 31
Killip Class	Class I Class II Class III Class IV	0 21 43 64
Cardiac arrest at admission		43
Elevated Cardiac Bio-markers		15
ST-segment deviation		30

Do's

• Administer a loading dose followed by a maintenance dose of clopidogrel, ticagrelor or prasugrel (if PCI is planned) as initial treatment instead of aspirin among patients with gastrointestinal intolerance or hypersensitivity reaction to aspirin.

• Administer sublingual nitroglycerin in patients with ischemic chest pain; however, administer IV nitroglycerin among patients with persistent chest pain after three sublingual nitroglycerin.

• Discontinue NSAID drugs immediately.

Don'ts

• Do not administer IV GP IIb/IIIa inhibitors to patients with low risk of ischemic events or at high risk of bleeding and who are already on aspirin and P2Y12 receptor inhibitors therapy.

• Do not administer prasugrel among patients with prior history of strokes or TIAs.

• Do not administer IV beta-blockers among hemodynamically unstable patients.

• Do not administer a complete dose of prasugrel among patients under 60kg (132lbs) due to high exposure to the active metabolite. They should receive half the dose of prasugrel although there is no evidence that half the dose is as effective as a complete dose.

• Do not administer fibrinolytic therapy to patients with unstable angina.

• Do not administer abciximab for patients not scheduled for PCI.

References

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