What is the appropriate management for a patient presenting with Non-ST-Elevation Myocardial Infarction (NSTEMI)?

Management of Non-ST-Elevation Myocardial Infarction (NSTEMI)

Immediately administer aspirin 150-300 mg orally (non-enteric, chewed or swallowed), initiate parenteral anticoagulation, admit to a monitored unit with continuous rhythm monitoring, and perform risk stratification to determine timing of invasive coronary angiography within 2-48 hours based on clinical presentation. 1, 2, 3

Immediate Initial Management (First Hour)

ECG and Monitoring

• Obtain a 12-lead ECG within 10 minutes of first medical contact and have it interpreted immediately by an experienced physician 1, 4
• Admit all patients to a monitored unit with continuous cardiac rhythm monitoring for at least 24 hours (longer if at increased risk for arrhythmias) 1, 3
• Obtain additional 12-lead ECGs if recurrent symptoms occur or diagnostic uncertainty exists 1, 4
• Consider additional ECG leads (V3R, V4R, V7-V9) if ongoing ischemia is suspected when standard leads are inconclusive 1

Cardiac Biomarkers

• Measure high-sensitivity cardiac troponin (hs-cTn) at presentation (0 hours) and at 1 hour using the ESC 0h/1h algorithm 1, 4
• If the first two troponin measurements are inconclusive and clinical presentation still suggests ACS, perform additional testing at 3 hours 1, 4
• Continue serial hs-cTn measurements for prognostic stratification 1

Oxygen and Symptomatic Relief

• Administer supplemental oxygen only if arterial oxygen saturation is <90%; routine oxygen is not indicated 3
• Give sublingual or intravenous nitroglycerin for ongoing ischemic chest pain 1, 3
• Critical contraindications to nitroglycerin: systolic blood pressure <90 mmHg or ≥30 mmHg below baseline, severe bradycardia (<50 bpm), tachycardia (>100 bpm without heart failure), right ventricular infarction, or phosphodiesterase inhibitor use within 24 hours (sildenafil) or 48 hours (tadalafil) 1, 3
• Administer morphine sulfate intravenously only for uncontrolled ischemic chest pain despite nitroglycerin, with additional therapy to manage underlying ischemia 1, 2

Antiplatelet Therapy

Aspirin (Mandatory for All Patients)

• Loading dose: 150-300 mg orally (non-enteric formulation, chewed or swallowed) or 75-250 mg intravenously 1, 3
• Maintenance dose: 75-100 mg daily indefinitely 1, 2, 3

P2Y12 Inhibitor Selection (Add to Aspirin)

Ticagrelor is the preferred P2Y12 inhibitor for all NSTEMI patients regardless of invasive or conservative strategy: 1, 2, 3, 4

• Loading dose: 180 mg orally
• Maintenance dose: 90 mg twice daily
• Continue for 12 months unless contraindicated or excessive bleeding risk 1, 2

Prasugrel is preferred for P2Y12 inhibitor-naïve patients proceeding to PCI: 1, 4

• Loading dose: 60 mg orally
• Maintenance dose: 10 mg daily (5 mg daily for patients ≥75 years or weight <60 kg)
• Do not use if history of stroke or TIA 1

Clopidogrel should only be used when prasugrel or ticagrelor are unavailable, not tolerated, or contraindicated: 1, 4, 5

• Loading dose: 300-600 mg orally
• Maintenance dose: 75 mg daily
• Critical caveat: Clopidogrel is a prodrug requiring CYP2C19 metabolism; patients who are CYP2C19 poor metabolizers have reduced antiplatelet effect and should receive an alternative P2Y12 inhibitor 5
• Avoid concomitant use with omeprazole or esomeprazole as they significantly reduce clopidogrel's antiplatelet activity 5

Timing of P2Y12 Inhibitor Administration

• Do not routinely pre-treat with a P2Y12 inhibitor before coronary anatomy is known if early invasive management is planned 1
• Administer loading dose after coronary anatomy is defined and revascularization strategy is determined 1, 2

Glycoprotein IIb/IIIa Inhibitors

• Do not use GP IIb/IIIa antagonists in patients when coronary anatomy is not known 1, 2

Anticoagulant Therapy

Immediate Parenteral Anticoagulation (Mandatory for All Patients)

All NSTEMI patients require parenteral anticoagulation in addition to antiplatelet therapy at the time of diagnosis: 1, 2, 4

Agent Selection

First-line options: 1, 2, 4

• Unfractionated heparin (UFH): Continue for at least 48 hours or until discharge if given before diagnostic angiography
• Enoxaparin: Continue for duration of hospitalization, up to 8 days, if given before diagnostic angiography
• Fondaparinux: Continue for duration of hospitalization, up to 8 days, if given before diagnostic angiography
• Bivalirudin: Alternative option, particularly for patients at increased bleeding risk 2, 4

Special Considerations for Anticoagulation

• For patients with severe renal impairment or end-stage renal disease: UFH is preferred as it does not accumulate with renal dysfunction 2
• For patients with moderate renal impairment: Enoxaparin requires dose adjustment; bivalirudin or UFH may be preferred 2
• For patients with increased bleeding risk: Fondaparinux or bivalirudin are reasonable first choices 2
• Critical pitfall: If fondaparinux is used, add UFH during PCI to prevent catheter thrombosis 2, 4
• Do not switch between anticoagulants as this increases bleeding risk 2

Risk Stratification and Invasive Strategy Timing

Immediate Invasive Strategy (<2 Hours)

Perform immediate coronary angiography for very high-risk patients with: 2, 4

• Refractory or recurrent angina despite intensive medical therapy
• Hemodynamic instability or cardiogenic shock
• Life-threatening arrhythmias (ventricular fibrillation or ventricular tachycardia)
• Mechanical complications of MI
• Acute heart failure

Early Invasive Strategy (<24 Hours)

Perform early coronary angiography for high-risk patients with: 1, 2, 3, 4

• Elevated cardiac biomarkers (troponin)
• Dynamic ST-segment or T-wave changes on ECG
• High GRACE score (>140) or high TIMI risk score
• Recurrent symptoms despite medical therapy
• Electrical instability

Delayed Invasive Strategy (24-48 Hours)

Perform coronary angiography within 24-48 hours for intermediate-risk patients without very high-risk features 2, 3

Conservative Strategy

A conservative (ischemia-guided) strategy is appropriate for: 2, 3

• Lower-risk patients without ongoing ischemia
• Patients with significant comorbidities where invasive risks outweigh benefits
• Patient preference after informed discussion

Beta-Blocker Therapy

Initiation

• Oral beta-blockers should be initiated to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility 1, 3
• Oral route is preferred over intravenous administration 3

Contraindications to Beta-Blockers

Do not administer beta-blockers (especially intravenous) to patients with: 1, 3

• Signs of heart failure or low-output state
• Increased risk for cardiogenic shock
• PR interval >0.24 seconds, second- or third-degree heart block
• Active asthma or reactive airway disease
• Severe bradycardia or hypotension

Imaging

Echocardiography

• Perform echocardiography to evaluate regional and global left ventricular function and rule out differential diagnoses 1, 4
• In patients with cardiac arrest or hemodynamic instability of presumed cardiovascular origin, perform echocardiography immediately following 12-lead ECG 1

Non-Invasive Stress Testing or CCTA

• For patients with no recurrence of chest pain, normal ECG, and normal cardiac troponin but still suspected ACS, perform non-invasive stress test (preferably with imaging) or coronary CT angiography (CCTA) before deciding on invasive approach 1
• CCTA is recommended as an alternative to invasive coronary angiography to exclude ACS when there is low-to-intermediate likelihood of CAD and when troponin and/or ECG are normal or inconclusive 1

Post-Angiography Management

If PCI is Performed

• Continue aspirin indefinitely 2, 3, 4
• Administer P2Y12 inhibitor loading dose if not given before diagnostic angiography 2, 3, 4
• Continue dual antiplatelet therapy (aspirin + P2Y12 inhibitor) for 12 months 2, 3

If CABG is Planned

• Continue aspirin perioperatively 2, 3, 4
• Stop clopidogrel 5-7 days before elective CABG 2, 3, 4
• Stop prasugrel at least 7 days before surgery 4
• Stop ticagrelor at least 5 days before surgery 4

If Medical Management is Selected

• Continue aspirin indefinitely 2, 3
• Administer P2Y12 inhibitor loading dose if not given before diagnostic angiography 2, 3
• Continue dual antiplatelet therapy for 12 months 2

Long-Term Secondary Prevention

Left Ventricular Function Assessment

• Measure left ventricular ejection fraction (LVEF) in all patients 2, 3, 4
• If LVEF ≤0.40, consider diagnostic angiography if not already performed 2, 3
• If LVEF >0.40, consider stress testing for risk stratification 2, 3

ACE Inhibitors or ARBs

• Initiate ACE inhibitors for patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes 1, 2, 3
• Administer orally within the first 24 hours in the absence of hypotension (systolic BP <100 mmHg or >30 mmHg below baseline) or contraindications 1
• Do not give intravenous ACE inhibitors within the first 24 hours due to increased risk of hypotension (exception: refractory hypertension) 1, 3
• Consider ARBs for patients intolerant to ACE inhibitors 2, 3, 4

Beta-Blockers

• Continue beta-blockers indefinitely in all NSTEMI patients without contraindications 3

Statin Therapy

• Initiate high-intensity statin therapy regardless of baseline LDL levels 2, 3

Long-Term Oral Anticoagulation (If Indicated)

For patients requiring long-term oral anticoagulation (e.g., atrial fibrillation): 2, 6

• Triple antithrombotic therapy (oral anticoagulant + aspirin + P2Y12 inhibitor) for the shortest duration possible, typically 1 week to 1 month (or until hospital discharge)
• Dual therapy (oral anticoagulant + P2Y12 inhibitor, preferably clopidogrel) for up to 1 year
• Monotherapy with oral anticoagulant thereafter
• Prefer direct oral anticoagulants (DOACs) over warfarin 6
• Minimize triple therapy duration as bleeding risk increases from 4-6% with dual therapy to 10-14% with triple therapy 2

Critical Contraindications and Pitfalls to Avoid

Absolute Contraindications

• NSAIDs (except aspirin) should not be administered during hospitalization due to increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture 1, 2, 3
• Fibrinolytic therapy is contraindicated in NSTEMI patients without ST-segment elevation 3

Calcium Channel Blockers

• Do not administer immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 1, 3
• Long-acting nondihydropyridine calcium channel blockers are reasonable only for recurrent ischemia after beta-blockers and nitrates have been fully used 1

Intravenous Beta-Blockers

• Avoid intravenous beta-blockers in patients with signs of heart failure, low-output state, or risk factors for cardiogenic shock 1, 3

Drug Interactions

• Avoid concomitant use of clopidogrel with omeprazole or esomeprazole as they significantly reduce antiplatelet activity 5
• Avoid strong CYP2C19 inducers with clopidogrel as they may potentiate bleeding risk 5