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

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

All NSTEMI patients require immediate aspirin 150-300 mg, parenteral anticoagulation, continuous cardiac monitoring in a monitored unit, and risk stratification to determine timing of invasive coronary angiography within 2-72 hours based on clinical risk factors. 1

Immediate Initial Management (First 10 Minutes)

• Obtain a 12-lead ECG within 10 minutes of first medical contact and have it interpreted immediately by an experienced physician 1, 2
• Administer aspirin 150-300 mg orally (non-enteric formulation, chewed) immediately upon presentation 1, 3, 2
• Admit to a monitored unit with continuous rhythm monitoring for at least 24 hours or until PCI, whichever comes first 1, 3
• Administer supplemental oxygen only if arterial oxygen saturation is <90% 3
• Consider sublingual or intravenous nitroglycerin for ongoing ischemic chest pain, unless systolic BP <90 mmHg, heart rate <50 or >100 bpm without heart failure, right ventricular infarction, or recent phosphodiesterase inhibitor use (sildenafil within 24h, tadalafil within 48h) 1, 3
• Consider morphine sulfate intravenously for uncontrolled ischemic chest discomfort despite nitroglycerin 3

Diagnostic Workup (First Hour)

• Measure high-sensitivity cardiac troponin (hs-cTn) at 0 hours and 1 hour using the ESC 0h/1h algorithm for rapid diagnosis 1, 2
• If the first two troponin measurements are inconclusive and clinical suspicion remains high, obtain additional troponin at 3 hours 1, 2
• Perform echocardiography to evaluate left ventricular regional and global function and exclude differential diagnoses 1, 2
• Obtain additional 12-lead ECG with leads V3R, V4R, V7-V9 if ongoing ischemia is suspected when standard leads are inconclusive 1

Antiplatelet Therapy

Aspirin

• Continue aspirin 75-100 mg daily indefinitely after the initial loading dose 1, 3, 2

P2Y12 Inhibitor Selection

A P2Y12 inhibitor must be added to aspirin and maintained for 12 months unless contraindicated or excessive bleeding risk exists. 1, 2

The preferred agents in order of priority are:

1. Ticagrelor (first-line choice): 180 mg loading dose, then 90 mg twice daily, regardless of invasive or conservative strategy 1, 3, 2
2. Prasugrel (for PCI patients only): 60 mg loading dose, then 10 mg daily (reduce to 5 mg daily if age ≥75 years or weight <60 kg); contraindicated in patients with prior stroke or TIA 1, 2, 4
3. Clopidogrel (only if ticagrelor/prasugrel unavailable or contraindicated): 300-600 mg loading dose, then 75 mg daily 1, 2

Critical caveat: Do NOT routinely pre-treat with P2Y12 inhibitors before coronary anatomy is known if early invasive management is planned 1. However, ticagrelor may be initiated regardless of strategy 1, 2.

Clopidogrel-specific warning: Patients who are CYP2C19 poor metabolizers have reduced conversion to active metabolite and diminished antiplatelet effect; consider alternative P2Y12 inhibitor 4. Avoid concomitant omeprazole or esomeprazole as they significantly reduce clopidogrel's antiplatelet activity 4.

Anticoagulation Strategy

Parenteral anticoagulation is mandatory for all NSTEMI patients in addition to antiplatelet therapy. 1, 3, 2

Agent Selection:

• Unfractionated heparin (UFH): Loading dose 60 U/kg IV bolus (max 4,000 U), continue for at least 48 hours or until discharge 1, 3
• Enoxaparin: 30 mg IV bolus followed by 1 mg/kg subcutaneous every 12 hours, continue for duration of hospitalization up to 8 days 1, 3, 2
• Fondaparinux: 2.5 mg subcutaneous once daily, continue for duration of hospitalization up to 8 days 1, 3, 2
• Bivalirudin: 0.1 mg/kg bolus with 0.25 mg/kg/h infusion (adjust based on strategy) 1, 3

Critical pitfall: If fondaparinux is used, must add UFH 50-60 U/kg IV bolus during PCI to prevent catheter thrombosis 3. Do not switch between anticoagulants as this increases bleeding risk 3.

Do NOT use GP IIb/IIIa inhibitors routinely before coronary anatomy is known due to increased bleeding risk without reduction in ischemic events 1, 3.

Risk Stratification and Timing of Invasive Strategy

Immediate Invasive Strategy (<2 hours):

Indicated for very high-risk patients with: 1, 3

• Refractory or recurrent angina despite medical therapy
• Hemodynamic instability or cardiogenic shock
• Life-threatening arrhythmias or cardiac arrest
• Mechanical complications of MI
• Acute heart failure

Early Invasive Strategy (<24 hours):

Indicated for high-risk patients with: 1, 3, 2

• Elevated cardiac biomarkers (troponin)
• Dynamic ST-segment or T-wave changes
• GRACE score >140 or high TIMI risk score
• Diabetes mellitus
• Renal insufficiency (eGFR <60 mL/min/1.73m²)
• Left ventricular ejection fraction <40%
• Recent PCI or prior CABG

The RIDDLE-NSTEMI trial demonstrated that immediate intervention (<2 hours) reduced death or new MI at 30 days (4.3% vs 13%, p=0.008) and 1 year (6.8% vs 18.8%, p=0.002) compared to delayed intervention, primarily by preventing pre-catheterization MI. 5

Delayed Invasive Strategy (24-72 hours):

Appropriate for intermediate-risk patients without ongoing ischemia or high-risk features 3, 2

Conservative Strategy:

Consider for low-risk patients without elevated troponin, ongoing ischemia, or high-risk features, or patients with significant comorbidities where invasive risks outweigh benefits 3, 2

Post-Angiography Management

If PCI Performed:

• Continue aspirin indefinitely 3, 2
• Administer P2Y12 inhibitor loading dose if not given before angiography 3, 2
• Continue dual antiplatelet therapy for 12 months minimum regardless of stent type 3, 4

If CABG Planned:

• Continue aspirin 3, 2
• Stop clopidogrel 5-7 days before surgery 1, 3, 2
• Stop prasugrel at least 7 days before surgery 3, 2
• Stop ticagrelor at least 5 days before surgery 3, 2

If Medical Management Selected:

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

Long-Term Secondary Prevention

• Measure left ventricular ejection fraction (LVEF) in all patients 3, 2
• Initiate beta-blockers for all patients without contraindications to reduce myocardial oxygen demand 3, 2
• Initiate ACE inhibitors for patients with heart failure, LVEF <40%, hypertension, or diabetes 3, 2
• Consider ARBs for ACE inhibitor-intolerant patients 3, 2
• Initiate high-intensity statin therapy regardless of baseline LDL levels 3
• If LVEF ≤40%, consider diagnostic angiography if not already performed 3
• If LVEF >40%, consider stress testing for risk stratification 3, 2

Critical Contraindications and Pitfalls

• NEVER administer NSAIDs (except aspirin) during hospitalization due to increased mortality, reinfarction, hypertension, heart failure, and myocardial rupture risk 1, 3
• NEVER give immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 1, 3
• NEVER administer intravenous ACE inhibitors within the first 24 hours due to hypotension risk 1, 3
• NEVER give intravenous beta-blockers to patients with signs of heart failure, low-output state, or cardiogenic shock risk 1
• NEVER administer nitrates to patients with systolic BP <90 mmHg, severe bradycardia (<50 bpm), tachycardia (>100 bpm) without heart failure, right ventricular infarction, or recent phosphodiesterase inhibitor use 1

Special Considerations for Patients Requiring Long-Term Anticoagulation

For patients with atrial fibrillation or other indications requiring oral anticoagulation:

• Use triple antithrombotic therapy (oral anticoagulant + aspirin + clopidogrel) for the shortest duration possible, typically 1 week to 1 month 3, 6
• Transition to dual therapy (oral anticoagulant + clopidogrel) for up to 1 year 3, 6
• Continue oral anticoagulant monotherapy thereafter 6
• Prefer DOACs over warfarin when possible 3, 6