Unstable angina/ NSTEMI resident survival guide

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

Unstable angina/ NSTEMI Resident Survival Guide Microchapters
Overview
Causes
Ischemia-guided Strategy vs. Invasive Strategy
FIRE
Revascularization Therapy
Pre-Discharge Care
Dosing of Parenteral Anticoagulants During PCI
Do's
Don'ts

Overview

Unstable angina and non ST elevation myocardial infarction (NSTEMI) belong to two different ends of the spectrum of acute coronary syndrome. These conditions have a similar clinical presentation characterized by an acute onset of chest pain that starts on minimal exertion, rest or sleep, lasts at least 20 minutes (but usually less that half an hour) and, is not relieved by medications or rest. NSTEMI is differentiated from unstable angina by the presence of elevated cardiac biomarkers secondary to myocardial injury. Unstabel angina and NSTEMI might not be differentiated early following the occurrence of symptoms because cardiac biomarkers may require a few hours to rise.

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

Myocardial Infarction

• Atherosclerotic plaque rupture and subsequent coronary thrombus (most common cause)
• Coronary artery spasm
• Arrhythmia
• Post-myocardial infarction
• Post-percutaneous coronary intervention
  • Abrupt closure
  • Loss of side branch
  • Distal embolization
  • Restenosis
  • Stent thrombosis
• Post-coronary artery bypass graft
  • Graft closure
  • New lesion in the graft

For a complete list of causes, click here for unstable angina and here for NSTEMI.

Ischemia-guided Strategy vs. Invasive Strategy

Shown below is a table that lists the factors that are associated with appropriate selection of invasive strategy vs. ischemia-guided strategy among patients with NSTE-ACS.

Strategy	Subcategory	Clinical Findings
Invasive	Immediate invasive (within 2 hours)	❑ Refractory angina
		❑ Signs or symptoms of either heart failure or new/worsening mitral regurgitation
		❑ Hemodynamic instability
		❑ Recurrent angina or ischemia at rest or with low-level activities despite intensive pharmacologic therapy
	Early invasive (within 24 hours)	❑ None of the requirements for immediate invasive strategy were met
		❑ GRACE risk score > 140
		❑ Temporal changes in troponin level
		❑ New/presumably new ST-segment depression
	Delayed invasive (within 25-72 hours)	❑ None of the requirements for immediate/early invasive strategies was met
		❑ Known history of diabetes mellitus
		❑ Known history of renal insufficiency (defined as eGFR < 60 ml/min/1.73 m2)
		❑ Reduced LV systolic function (LVEF < 40%)
		❑ Early post-infarct angina
		❑ PCI within 6 months
		❑ History of prior CABG
		❑ GRACE risk score 109-140 or TIMI risk score ≥ 2
Ischemia-guided strategy		❑ None of the requirements for any of the invasive (either immediate, early, or delayed) strategies was met
		❑ Low-risk score (either GRACE risk score < 109 or TIMI risk score = 0-1)
		❑ Low-risk Troponin-negative female patients
		❑ Patient or clinician preference in the absence of high-risk features

^{Adapted from Amsterdam et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes. J Am Coll Cardiol. 2014;64(24):e139-e228}

FIRE: Focused Initial Rapid Evaluation

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention. The following algorithm is derived from the 2014 AHA/ACC guideline for the management of patients with Non-ST-elevation acute coronary syndromes (either unstable angina or non-ST-elevation myocardial infarction).

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 ❑ Located in retrosternal region ❑ Sensation of heaviness, tightness, pressure, or squeezing ❑ Duration> 10 minutes (but usually less than half an hour) ❑ Radiation to both arms, jaw, neck, back or epigastrium ❑ No relief with medications ❑ No relief with rest ❑ Progressively worsening ❑ Worse with exertion ❑ Associated symptoms of palpitations, nausea, vomiting, diaphoresis, dyspnea, abdominal pain,lightheadedness, or syncope ❑ Known personal history of CAD ❑ Family history of early CAD ❑ Known risk factors for CAD (dyslipidemia, HTN, diabetes, smoking, peripheral vascular disease) ❑ Perform a thorough cardiovascular physical examination and search for signs of myocardial ischemia, signs of HF, and signs of other non-ischemic causes of the patient's symptoms that might suggestive alternative diagnoses: ❑ Presence of S4 during cardiac auscultation ❑ Paradoxical splitting of S2 ❑ New-onset murmur suggestive of mitral regurgitation (late systolic murmur heard in mitral region) style="color:white;">NSTEMI]]

Perform diagnostic tests ❑ Perform ECG within 10 minutes of patient arrival to the ED (LOE: IC) ❑ No electrocardiographic changes. If high suspicion of ACS and normal ECG, repeat ECG every 15-30 minutes during the first hour (LOE: IC) ❑ ST-segment depression (carries the poorest prognosis) - If patient has anterior ST-segment depression indicative of true posterior MI, manage patient according to STEMI guidelines. ❑ Non specific ST / T wave changes ❑ T wave inversions ❑ Transient ST-segment elevation ❑ Findings on ECG that may mask signs of ischemia. If ANY of the following findings is present, use the Sgarbossa's criteria for the diagnosis of MI: ❑ LBBB ❑ Ventricular pacing ❑ Consider supplemental ECG leads V7 to V9 in patients whose initial ECG is non-diagnostic and who are at intermediate/high risk of ACS (LOE: IIB) ❑ Consider continuous ECG monitoring in patients whose initial ECG is non-diagnostic and who are at intermediate/high risk of ACS (LOE: IIB) ❑ Biomarkers of myocardial necrosis (either sensitive cardiac troponin assay or high-sensitivity cardiac troponin assay). Positive troponin is defined as either 1) troponin > 99th percentile of upper reference level, 2) serial increase or decrease ≥ 20% if initial value is elevated, or 3) change ≥ 3 standard deviations of variation around initial value if troponin below or close to 99th percentile ❑ Perform serial cardiac troponin (either I or T) at presentation and 3-6 hours after onset of symptoms (LOE: IA) ❑ Obtain an additional set of troponin levels if the patient had normal troponin levels on serial exam when there is an intermediate/high index of suspicion for ACS based on clinical presentation or ECG changes (LOE: IA) ❑ Consider an additional set of troponin levels on day 3-4 as a surrogate marker for infarct size and dynamics of necrosis (LOE: IIB) ❑ Biomarkers of heart failure ❑ Consider measurement of BNP or N-terminal pro-BNP to assess risk in patients with suspected ACS (LOE: IIB)

Rule out alternative life threatening diseases ❑ Aortic dissection (classical findings: back pain, interscapular pain, murmur of aortic regurgitation, pulsus paradoxus, hypotension, blood pressure discrepancy between the arms, classically > 15 mm Hg difference of SBP) ❑ Pulmonary embolism (classical findings: acute onset of dyspnea, tachycardia, tachypnea, hemoptysis, history of prior coagulopathies, such as DVT) ❑ Cardiac tamponade (classical findings: hypotension, jugular venous distention, muffled heart sounds, pulsus paradoxus) ❑ Tension pneumothorax (classical findings: sudden dyspnea, tachycardia, tachypnea,, recent history of chest trauma, unilateral absence of breath sound) ❑ Esophageal rupture (classical findings: vomiting, subcutaneous emphysema)

Assess the Patient's Prognosis ❑ Apply ANY one of the following risk scores to evaluate the patient's prognosis (LOE: IA) ❑ TIMI risk score, OR ❑ GRACE risk score

Does the patient have any of the following (at least one is sufficient to determine that the patient has high-risk features)? ❑ High risk score (defined as either TIMI > 1 OR GRACE score > 109) ❑ Signs or symptoms of HF or new/worsening mitral regurgitation ❑ Hemodynamic instability ❑ Sustained VT or VF ❑ New or presumably new ST-segment depression ❑ Known history of diabetes mellitus ❑ Known history of renal insufficiency (defined as eGFR < 60 min/min/1.72 m2) ❑ Reduced LV systolic function (LVEF < 40%) ❑ Recent PCI within 6 months ❑ History of prior CABG Refer to the table Ischemia-guided strategy vs. Invasive strategy for a detailed distinction between the two based on the patient's clinical findings.

No. The patient does NOT have ANY of the above high risk features.

Yes. The patient has at least one of the above high risk features

Follow an ischemia-guided strategy ❑ Administer dual antiplatelet therapy to all patients with NSTE ACS (aspirin plus only one P2Y12) ❑ Administer non-enteric-coated chewable aspirin PO 162-325 mg to all patients who have no contraindications to aspirin therapy as soon as possible following presentation (LOE: IA). Continue aspirin indefinitely at a maintenance dose of 81-162 mg daily (usually 81 mg preferred for maintenance dose, especially when co-administered with ticagrelor). Do not administer aspirin to patients who cannot tolerate aspirin (either hypersensitivity or GI distress). ❑ Administer a P2Y12 inhibitor (either clopidogrel or ticagrelor) for up to 12 months to NSTE ACS patients to patients with NSTE ACS (without contraindications) with either early invasive or ischemia-guided strategy. ❑ Ticagrelor: Loading dose of ticagrelor PO 180 mg followed by maintenance dose of ticagrelor 80 mg twice daily (LOE: IB) (preferred over clopidogrel for NSTE ACS patients who undergo early invasive or ischemia-guided strategy) (LOE: IIB) ❑ Clopidogrel: Loading dose of clopidogrel PO 300-600 mg followed by maintenance dose of clopidogrel 75 mg once daily (LOE: IB), OR ❑ Titrate oxygen via nasal cannula to SpO2 > 90% for patients with saturation <90%, respiratory distress, or other high-risk features of hypoxemia (LOE: IC) Caution in COPD patients: maintain an oxygen saturation between 88% and 92%. ❑ Administer nitroglycerin ❑ Administer sublingual nitroglycerin (0.3 to 0.4 mg, every 5 minutes for a total of 3 doses) then assess for further need to IV nitroglycerin (LOE: IC) ❑ Administer IV nitroglycerin in case of persistent chest pain despite PO nitroglycerin, heart failure, or hypertension (LOE: IB): 10 mcg/min, increase by 10 mcg/min every 3 to 5 minutes until symptom relief; in case no response at 20 mcg/min, increase by 10 microgram/minute and then by 20 microgram/minute ❑ Hold nitroglycerin is SBP < 100 mm Hg Contraindicated in suspected right ventricular MI, recent use of phosphodiesterase inhibitors (24 hours of sildenafil or vardenafil use or 48 hours of tadalafil use), decreased blood pressure 30 mmHg below baseline ❑ Administer ANY of the following PO beta-blockers (unless contraindicated) within 24 hours of ischemia and titrate to the heart rate and blood pressure (LOE: IA) Beta blocker is contraindicated in unstable/decompensated heart failure, low output states (bradycardia or hypotension), in patients at high risk of cardiogenic shock (defined as either old age > 70 years, HR > 110 bpm, SBP < 120 mm Hg, or late presentation), prolonged PR interval > 0.24 s, 2nd/3rd degree heart block without pacemaker, or active asthma/reactive airway disease. Reassess the patient's condition frequently to re-evaluate the eligibility of beta-blockage therapy (LOE: IC). ❑ Metoprolol succinate, OR PO: 50-200 mg twice daily ❑ Carvedilol, OR PO: 6.25 mg twice daily. Maximum dose 25 mg twice daily ❑ Bisoprolol PO: 5 mg once daily ❑ Consider PO non-dihydropyridine CCB (either verapamil or diltiazem) only if patients either cannot tolerate beta blockers, are allergic to beta blockers, or were administered beta blockers plus nitrates and have recurrent ischemia (LOE: IIC) ❑ Verapamil PO: 80-120 mg orally 3 times a day, OR ❑ Diltiazem PO: 30 to 60 mg orally 3 to 4 times a day ❑ Administer IV morphine if persistent symptoms (LOE: IIB) or pulmonary edema ❑ Initially, administer morphine IV 1-5 mg and monitor BP ❑ Add morphine IV 2-8 mg every 5 to 30 minutes, as needed ❑ Monitor for any adverse effects of morphine therapy, including hypotension, respiratory depression, nausea/vomiting. Administer naloxone o.4 mg to 2 mg IV if morphine therapy is associated with respiratory of circulatory depression ❑ Administer ANY of the following high-intensity statins to patients who have co contraindications to statin therapy (LOE: IA) ❑ Atorvastatin PO: 40-80 mg once daily ❑ Rosuvastatin PO: 20-40 mg once daily ❑ Administer ANY of the following anticoagulation therapies for all patients regardless of initial treatment strategy ❑ Enoxaparin 1 mg/kg subcutaneously twice daily from presentation until time of PCI or discharge (if no PCI is performed) (LOE: IA). Reduce the dose to 1 mg/kg subcutaneously once daily for patients with CrCl < 30 mL/min, OR ❑ Fondaparinux: 2.5 mg subcutaneously once daily continued for the duration of hospitalization or until PCI or discharge (if no PCI is performed) (LOE: IIB). If PCI is performed while the patient is on fondaparinux, add either UFH or bivalirudin to fondaparinux because of increased risk of catheter thrombosis (LOE: IB), OR ❑ Unfractionated hepatin (UFH) IV: Administer loading dose 60 IU/kg (maximum 4,000 IU) with initial infusion of 12 IU/kg/hour (maximum 1,000 IU/hour) adjusted per aPTT to maintain a therapeutic range per hospital protocol. Continue UFH for 48 hours or until PCI is performed (LOE: IB)

Follow an invasive strategy ❑ Administer dual antiplatelet therapy to all patients with NSTE ACS (aspirin plus only one P2Y12) ❑ Administer non-enteric-coated chewable aspirin PO 162-325 mg to all patients who have no contraindications to aspirin therapy as soon as possible following presentation (LOE: IA). Continue aspirin indefinitely at a maintenance dose of 81-162 mg daily (usually 81 mg preferred for maintenance dose, especially when co-administered with ticagrelor). Do not administer aspirin to patients who cannot tolerate aspirin (either hypersensitivity or GI distress). ❑ Administer a P2Y12 inhibitor (either clopidogrel or ticagrelor) for up to 12 months to NSTE ACS patients to patients with NSTE ACS (without contraindications) with either early invasive or ischemia-guided strategy. ❑ Ticagrelor: Loading dose of ticagrelor PO 180 mg followed by maintenance dose of ticagrelor 80 mg twice daily (LOE: IB) (preferred over clopidogrel for NSTE ACS patients who undergo early invasive or ischemia-guided strategy) (LOE: IIB) ❑ Clopidogrel: Loading dose of clopidogrel PO 300-600 mg followed by maintenance dose of clopidogrel 75 mg once daily (LOE: IB), OR ❑ Titrate oxygen via nasal cannula to SpO2 > 90% for patients with saturation <90%, respiratory distress, or other high-risk features of hypoxemia (LOE: IC) Caution in COPD patients: maintain an oxygen saturation between 88% and 92%. ❑ Administer nitroglycerin ❑ Administer sublingual nitroglycerin (0.3 to 0.4 mg, every 5 minutes for a total of 3 doses) then assess for further need to IV nitroglycerin (LOE: IC) ❑ Administer IV nitroglyerin in case of persistent chest pain despite PO nitroglycerin, heart failure, or hypertenion (LOE: IB): 10 mcg/min, increase by 10 mcg/min every 3 to 5 minutes until symptom relief; in case no response at 20 mcg/min, increase by 10 mcg/min and then by 20 mcg/min ❑ Hold nitroglycerin is SBP < 100 mm Hg Contraindicated in suspected right ventricular MI, recent use of phosphodiesterase inhibitors (24 hours of sildenafil or vardenafil use or 48 hours of tadalafil use), decreased blood pressure 30 mmHg below baseline ❑ Administer ANY of the following PO beta-blockers (unless contraindicated) within 24 hours of ischemia and titrate to the heart rate and blood pressure (LOE: IA) Beta blocker is contraindicated in unstable/decompensated heart failure, low output states (bradycardia or hypotension), in patients at high risk of cardiogenic shock (defined as either old age > 70 years, HR > 110 bpm, SBP < 120 mm Hg, or late presentation), prolonged PR interval > 0.24 s, 2nd/3rd degree heart block without pacemaker, or active asthma/reactive airway disease. Reassess the patient's condition frequently to re-evaluate the eligibility of beta-blockage therapy (LOE: IC). ❑ Metoprolol succinate, OR PO: 50-200 mg twice daily ❑ Carvedilol, OR PO: 6.25 mg twice daily. Maximum dose 25 mg twice daily ❑ Bisoprolol PO: 5 mg once daily ❑ Consider PO non-dihydropyridine CCB (either verapamil or diltiazem) only if patients either cannot tolerate beta blockers, are allergic to beta blockers, or were administered beta blockers plus nitrates and have recurrent ischemia (LOE: IIC) ❑ Verapamil PO: 80-120 mg orally 3 times a day, OR ❑ Diltiazem PO: 30 to 60 mg orally 3 to 4 times a day ❑ Administer IV morphine if persistent symptoms (LOE: IIB) or pulmonary edema ❑ Initially, administer morphine IV 1-5 mg and monitor BP ❑ Add morphine IV 2-8 mg every 5 to 30 minutes, as needed ❑ Monitor for any adverse effects of morphine therapy, including hypotension, respiratory depression, nausea/vomiting. Administer naloxone o.4 mg to 2 mg IV if morphine therapy is associated with respiratory of circulatory depression ❑ Administer ANY of the following high-intensity statins to patients who have co contraindications to statin therapy (LOE: IA) ❑ Atorvastatin PO: 40-80 mg once daily ❑ Rosuvastatin PO: 20-40 mg once daily ❑ Administer ANY of the following anticoagulation therapies for all patients regardless of initial treatment strategy ❑ Enoxaparin 1 mg/kg subcutaneously twice daily from presentation until time of PCI or discharge (if no PCI is performed) (LOE: IA). Reduce the dose to 1 mg/kg subcutaneously once daily for patients with CrCl < 30 mL/min, OR ❑ Bivalirudin may only be used for patients with early invasive strategy. Loading dose bivalirudin 0.1 mg/kg loading followed by bivalirudin 0.25 mg/kg/hour until PCI (LOE: IB), OR ❑ Fondaparinux: 2.5 mg subcutaneously once daily continued for the duration of hospitalization or until PCI or discharge (if no PCI is performed) (LOE: IIB). If PCI is performed while the patient is on fondaparinux, add either UFH or bivalirudin to fondaparinux because of increased risk of catheter thrombosis (LOE: IB), OR ❑ Unfractionated hepatin (UFH) IV: Administer loading dose 60 IU/kg (maximum 4,000 IU) with initial infusion of 12 IU/kg/hour (maximum 1,000 IU/hour) adjusted per aPTT to maintain a therapeutic range per hospital protocol. Continue UFH for 48 hours or until PCI is performed (LOE: IB) ❑ Consider administration of GP IIb/IIIa in addition to dual antiplatelet therapy in high-risk (e.g. troponin positive) patients (LOE: IIB) ❑ Eptifibatide IV: Loading dose 180 microgram/kg bolus followed by a maintenance dose of 2 microgram/kg/minute ❑ Tirofiban dose for UA/NSTEMI (non-PCI): IV initial rate 0.4 microgram/kg/minute for 30 minutes then continued at infusion rate of 0.1 microgram/kg/minute

Does the patient meet ANY of the following findings to transfer to invasive strategy? ❑ Refractory angina, OR ❑ Angina at rest or with minimal activity, OR ❑ Objective evidence of ischemia (dynamic ECG changes or myocardial perfusion defect) by non-invasive testing, OR ❑ Presence of high prognostic risk (high TIMI or high GRACE score)

No. The patient does not have any of the above findings. The patient will continue to be managed according the the ischemia-guided strategy

Yes. The patient has at least of the above findings and will be transferred to the invasive strategy for revasculization

Perform Risk Stratification Before Discharge for Patients Who had an ischemia-guided strategy of NSTE-ACS ❑ Perform ANY of the following non-invasive testing among low/intermediate risk patients who have had no ischemia symptoms at rest/low-level activity for the past 12-24 hours (LOE: B):❑ Perform treadmill exercise testing (only if ECG is free of resting ECG changes that might alter the interpretation of the ECG results (LOE: IC) ), OR:❑ Perform Stress testing with imaging modality (if patients have resting ECG changes that might alter the interpretation of the ECG results (LOE: IB) ), OR ❑ Perform pharmacologic stress testing with imaging if patient has physical limitations (LOE: IC)

Proceed to pre-discharge care

Proceed to revascularization therapy

Revascularization Therapy

Confirmed NSTE ACS (either unstable angina or NSTEMI)

Ischemia-guided strategy

Early invasive strategy

Was pharmacologic therapy for ischemia-guided strategy effective? If the patient has ANY of the following findings, pharmacologic therapy is considered ineffective: ❑ Refractory angina, OR ❑ Angina at rest or with minimal activity, OR ❑ Objective evidence of ischemia (dynamic ECG changes or myocardial perfusion defect) by non-invasive testing, OR ❑ Presence of high prognostic risk (either high TIMI risk score > 1 or high GRACE score > 109)

Yes. Pharmacologic therapy was effective

No. Pharmacologic therapy was not effective

Proceed to pre-discharge care

Revascularization. Use SYNTAX score to determine if patient will undergo PCI or CABG

PCI with stenting

CABG

Continue the following drugs ❑ Administer/Continue non-enteric coated aspirin PO 81-325 mg before PCI (LOE: IA) ❑ Administer loading dose of ANY P2Y12 inhibitor (either clopidogrel, ticagrelor, or prasugrel) in addition to aspirin (LOE: IB) ❑ Clopidogrel 600 mg loading dose (LOE: IB), OR ❑ Ticagrelor 180 mg loading dose (LOE: IB), OR ❑ Prasugrel 60 mg loading dose (LOE: IB) Prasugrel contraindicated in patients with a history of prior stroke/TIA ❑ Continue anticoagulant (either UFH (LOE: IB), enoxaparin (LOE: IA), or fondaparinux (LOE: IB)). To view the dose of each anticoagulant during PCI, click here ❑ Administer/continue ANY GPIIb/IIIa at PCI dose only among patients with high risk features (with adequate clopidogrel or ticagrelor pretreatment (LOE: IA) or without adequate clopidogrel or ticagrelor pretreatment (LOE: IIB) who were not treated with bivalirudin at the time of PCI ❑ Abciximab PCI dose: IV 0.25 mg/kg bolus dose administered 10-60 minutes before PCI followed by 0.125 microgram/kg/minute maintenance dose (maximum 10 microgram/minute) for 12 hours, OR ❑ Eptifibatide PCI double-bolus dose: IV bolus 180 microgram/kg immediately before PCI, then another IV 180 microgram/kg bolus 10 minutes after first bolus, followed by IV 2 microgram/kg/min infusion, OR ❑ Tirofiban PCI dose: IV bolus 25 microgram/kg over 3 minutes at time of procedure followed by infusion of 0.15 microgram/kg/minute continued for 18-24 hours

Continue the following drugs ❑ Continue aspirin (LOE: IA)

Discontinue the following drugs ❑ Discontinue P2Y12 inhibitor (either clopidogrel or ticagrelor) 5 days before elective CABG / up to 24 hours in case of urgent CABG (LOE: IB) ❑ Discontinue prasugrel 7 days before elective CABG / before 7 days in case of urgent CABG ❑ Discontinue eptifibatide/tirofiban at least 2-4 hours before CABG (LOE: IB) ❑ Discontinue abciximab at least 12 hours before CABG (LOE: IB)

Proceed to pre-discharge care

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

❑ Counsel the patient on lifestyle change and signs/symptoms of myocardial ischemia and MI, including presenting to ED for suggestive symptoms > 3-5 minutes ❑ Refer patient to comprehensive cardiovascular rehabilitation program ❑ Administer the following medications in patients without contraindications: Dual Antiplatelet Therapy ❑ Administer maintenance aspirin PO 81-325 mg indefinitely (low dose preferred) (LOE: IA) Do not administer aspirin to patients with either hypersensitivity to aspirin or GI distress. ❑ Administer ANY of the following antiplatelet agents in addition to aspirin ❑ Clopidogrel 75 mg once daily (LOE: IIB), OR ❑ Ticagrelor 90 mg twice daily (LOE: IIB), OR ❑ Prasugrel 10 mg once daily (only in PCI patients) (LOE: IIB) Continue ANY of clopidogrel, ticagrelor, or prasugrel up to 12 months for patients without PCI and for at least 12 months for patients with stent (either bare metal stent (BMS) or drug-eluting stent (DES) ). Early discontinuation or prolonged use of non-aspirin antiplatelet agents is reasonable based on patient risk of bleeding Nitroglycerin ❑ Administer 1 dose of sublingual or spray nitroglycerin to all patients post-NSTE ACS with angina lasting more than 1 minute. Prescribe nitroglycerin with verbal and written instruction for its administration (LOE: IC) Statin ❑ Administer ANY of the following high-intensity statins indefinitely post-NSTE ACS ❑ Atorvastatin 40-80 mg PO once daily, OR ❑ Rosuvastatin 20-40 mg PO once daily Beta blockers ❑ Metoprolol tartrate, OR ❑ Starting dose: 25-50 mg PO every 6 to 12 hour ❑ Then, metoprolol tartrate twice daily or metoprolol succinate once daily for 2-3 days ❑ Titate up to maximum dose of 200 mg daily ❑ Carvedilol ❑ Starting dose: 6.25 mg PO twice daily ❑ Titrate up to maximum dose of 25 mg twice daily ❑ Bisoprolol ❑ Starting dose: 5 mg PO once daily Non-dihydropyridine calcium channel blockers in select patients ❑ Administer ANY of the non-dihydropyridine CCB only among patients who either cannot tolerate beta blockers, are allergic to beta blockers, or were administered beta blockers plus nitrates and have recurrent ischemia. Patients administered CCB should not have contraindications to CCB therapy (e.g. heart failure or LV dysfunction) ❑ Verapamil: 80-120 mg PO 3 times a day, OR ❑ Diltiazem: 30-60 mg PO 3-4 times a day ACE inhibitors or ARBs ❑ Administer ACE inhibitors indefinitely to patients with LVEF < 40% and among patients with HTN, diabetes, or stable CKD unless contraindicated (LOE: IA) ❑ If ACEI cannot be tolerated, administer ARB to patients with HF or MI with LVEF < 40% (LOE: IA) Aldosterone blocker ❑ Administer ANY aldosterone blocker to patients post-MI receiving therapeutic doses of ACEI and beta blockers with either LVEF <40%, diabetes, or HF (LOE: IA). Aldosterone blockers are contraindicated in significant renal insufficiency (defined as serum Cr > 2.5 mg/dL in men or > 2 mg/dL in women) or hyperkalemia (K > 5 mEq/L). ❑ Spironolactone: Starting dose 25 mg PO once daily. Increase dose to 50 mg once daily if the patient remains symptomatic at 6 weeks of therapy (reassess renal function and K level before increasing dose), OR ❑ Eplerenone: Starting dose 25 mg PO once daily (or 12.5 mg for elderly patients). Increase dose to 50 mg once daily (or 25 mg for elderly patients) if the patient remains symptomatic at 4 weeks of therapy (reassess K level before increasing dose) Individualize antiplatelet and anticoagulation therapy for NSTE ACS patients already receiving chronic anticoagulation ❑ Administer PPI therapy to patients who require triple antithrombotic therapy (anticoagulant plus aspirin plus P2Y12 inhibitor) with history of GI bleeding (LOE: IC) or without a history of GI bleeding (LOE: IIC) ❑ Administer warfarin to target an INR=2-2.5 among patients also receiving dual antiplatelet therapy (aspirin plus P2Y12 inhibitor) (LOE: IIC) Administer vaccinations ❑ Administer pneumococcal vaccine to patients older than 65 years of age and among high-risk patients with CV disease (LOE: IB) ❑ Administer influenza vaccine annually to all patients with CV disease (LOE: IC) Perform Risk Stratification Before Discharge for Patients Who had an ischemia-guided strategy of NSTE-ACS ❑ Perform ANY of the following non-invasive testing among low/intermediate risk patients who have had no ischemia symptoms at rest/low-level activity for the past 12-24 hours (LOE: B) ❑ Perform treadmill exercise testing (only if ECG is free of resting ECG changes that might alter the interpretation of the ECG results (LOE: IC) ), OR ❑ Perform Stress testing with imaging modality (if patients have resting ECG changes that might alter the interpretation of the ECG results (LOE: IB) ), OR ❑ Perform pharmacologic stress testing with imaging if patient has physical limitations (LOE: IC)

Dosing of Parenteral Anticoagulants During PCI

Anticoagulant	Patients who have received prior anticoagulant therapy	Patients who have NOT received prior anticoagulant therapy
Enoxaparin	For prior treatment with enoxaparin, if last SC dose was administered 8 12 h earlier or if <2 therapeutic SC doses of enoxaparin have been administered, an IV dose of enoxaparin 0.3 mg/kg should be given If the last SC dose was administered within prior 8 h, no additional enoxaparin should be given	0.5 mg/kg–0.75 mg/kg IV loading dose
Bivalirudin	For patients who have received UFH, wait 30 min, then give 0.75 mg/kg IV loading dose, then 1.75 mg/kg/h IV infusion For patients already receiving bivalirudin infusion, give additional loading dose 0.5 mg/kg and increase infusion to 1.75 mg/kg/h during PCI	0.75 mg/kg loading dose, 1.75 mg/kg/h IV infusion
Fondaparinux	For prior treatment with fondaparinux, administer additional IV treatment with anticoagulant possessing anti-IIa activity, considering whether GPI receptor antagonists have been administered	N/A
UFH	IV GPI planned: additional UFH as needed (e.g., 2,000–5,000 U) to achieve activated clotting time (ACT) of 200-250 seconds No IV GPI planned: additional UFH as needed (e.g., 2,000–5,000 U) to achieve ACT of 250–300 s for HemoTec, 300-350 s for Hemochron	IV GPI planned: 50–70 U/kg loading dose to achieve ACT of 200-250 s No IV GPI planned: 70–100 U/kg loading dose to achieve target ACT of 250–300 s for HemoTec, 300–350 s for Hemochron

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.

• If fondaparinux is chosen to be administered ad the anticoagulant therapy during PCI, co-administer another antocoagulant with factor IIa activity such as UFH.

Don'ts

• Do not administer fondaparinux as the sola anticoagulant to support PCI in patients with NSTE ACS due to increased risk of catheter thrombosis.
• Do not administer anticoagulation therapy following PCI unless there is compelling reason to continue such therapy.
• 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 NSAIDs to patients post-NSTE ACS. Attempt managing musculoskeletal pains using either acetaminophen, non-acetylated salicylates, tramadol, or small doses of narcotics before considering NSAIDs (first consider non-selective NSAIDs then selective NSAIDs)
• Do not administer hormone therapy (estrogen with out without progestin) to patients for secondary prevention of coronary events in post-menopausal women.
• Do not administer vitamin supplements (e.g. vitamin E, C, beta-carotene, folic acid, or vitamin B6/B12) for secondary prevention of NSTE ACS.
• Do not administer prasugrel to patients with prior history of strokes or TIA.

• 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.

• Do not administer 2 P2Y12 receptor inhibitors, even in the presence of hypersensitivity or GI interoperability to aspirin.

References

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