What is the recommended acute management for a patient presenting with non‑ST‑elevation myocardial infarction?

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

All patients presenting with NSTEMI require immediate dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor), parenteral anticoagulation, high-intensity statin therapy, and risk-stratified invasive coronary angiography within 2-72 hours depending on clinical presentation. 1

Immediate Diagnostic Evaluation

• Obtain 12-lead ECG within 10 minutes of presentation to confirm non-ST-elevation pattern and identify dynamic ST-segment or T-wave changes 1
• Measure high-sensitivity troponin at 0 and 1 hour using a validated algorithm, or at 0 and 3 hours if the 1-hour protocol is unavailable; additional testing after 3-6 hours is indicated if initial measurements are inconclusive 1
• Perform echocardiography to evaluate regional and global left ventricular function and exclude mechanical complications or differential diagnoses 1
• Calculate GRACE score for risk stratification to determine the timing of invasive strategy 1, 2

Antiplatelet Therapy (Start Immediately)

Aspirin

• Administer aspirin 150-325 mg oral loading dose immediately (or 75-250 mg IV if oral route unavailable), followed by 75-100 mg daily maintenance indefinitely 1, 3

P2Y12 Inhibitor Selection

Ticagrelor is the preferred first-line P2Y12 inhibitor for all moderate-to-high risk NSTEMI patients (those with elevated troponins), regardless of initial treatment strategy 1, 3:

• Loading dose: 180 mg orally
• Maintenance: 90 mg twice daily for 12 months 1, 3
• Ticagrelor can be started immediately, even in patients already receiving clopidogrel (discontinue clopidogrel when ticagrelor is initiated) 1, 3
• Contraindications: prior intracranial hemorrhage or active bleeding 1

Prasugrel is second-line and should only be used in patients proceeding to PCI after coronary anatomy is known 1, 3:

• Loading dose: 60 mg orally
• Maintenance: 10 mg daily (5 mg if body weight <60 kg) 1, 3
• Contraindications: prior stroke/TIA, age ≥75 years, body weight <60 kg, prior intracranial hemorrhage, or active bleeding 1, 3
• Critical pitfall: Never administer prasugrel before coronary anatomy is known, as this markedly increases bleeding risk if urgent CABG is required 1, 3

Clopidogrel is third-line for patients who cannot receive ticagrelor or prasugrel, or who require oral anticoagulation 1, 4:

• Loading dose: 300-600 mg orally (600 mg preferred for faster platelet inhibition)
• Maintenance: 75 mg daily 1, 4
• Note that clopidogrel effectiveness is reduced in CYP2C19 poor metabolizers; consider genetic testing if available 4

Anticoagulation (Start Immediately)

Select one anticoagulant and continue until revascularization or hospital discharge (up to 8 days) 1:

• Fondaparinux 2.5 mg subcutaneously once daily is preferred for patients managed medically or awaiting angiography 2

  • Contraindicated if CrCl <30 mL/min
  • Critical pitfall: When proceeding to PCI, add UFH or enoxaparin to prevent catheter thrombosis 2, 3

• Enoxaparin 1 mg/kg subcutaneously every 12 hours is an acceptable alternative 1, 2, 3

  • Reduce to 1 mg/kg every 24 hours if CrCl <30 mL/min
  • Reduce dose by 25% if CrCl 30-60 mL/min 3

• Unfractionated heparin (UFH) is recommended for patients proceeding directly to PCI 1, 2:

  • Bolus: 60 IU/kg (max 4000 units)
  • Infusion: 12 IU/kg/hour (max 1000 units/hour)
  • Adjust to therapeutic aPTT (1.5-2.0 × control) 1, 3

High-Intensity Statin Therapy

Start atorvastatin 80 mg daily immediately upon admission, regardless of baseline cholesterol levels 1, 2:

• Target LDL-C <1.4 mmol/L (<55 mg/dL) with at least 50% reduction from baseline 2
• Continue long-term to reduce recurrent events 1, 2

Risk-Stratified Timing of Invasive Strategy

Very high-risk patients require immediate angiography within 2 hours if any of the following are present 1, 2:

• Hemodynamic instability or cardiogenic shock
• Recurrent or ongoing chest pain refractory to medical treatment
• Life-threatening arrhythmias or cardiac arrest
• Mechanical complications of MI
• Acute heart failure with refractory angina or ST-segment deviation

High-risk patients require early angiography within 24 hours if any of the following are present 1, 2:

• Rise or fall in cardiac troponin compatible with MI
• Dynamic ST-segment or T-wave changes (symptomatic or silent)
• GRACE score >140

Intermediate-risk patients require angiography within 72 hours if any of the following are present 1, 2:

• Diabetes mellitus
• Renal insufficiency (eGFR <60 mL/min/1.73 m²)
• LVEF <40% or congestive heart failure
• Early post-infarction angina
• Recent PCI or prior CABG
• GRACE score 109-140
• Recurrent symptoms or ischemia on non-invasive testing

Glycoprotein IIb/IIIa Inhibitors (High-Risk Patients Only)

Consider adding a GP IIb/IIIa inhibitor (eptifibatide or tirofiban) in troponin-positive, high-risk patients undergoing early invasive strategy 1, 3:

• Eptifibatide: 180 µg/kg IV bolus, then 2 µg/kg/min infusion (reduce to 1.0 µg/kg/min if CrCl ≤50 mL/min) 3
• Tirofiban: 12 µg/kg IV bolus, then 0.14 µg/kg/min infusion (reduce to 6 µg/kg bolus plus 0.05 µg/kg/min if CrCl <30 mL/min) 3
• Discontinue 4 hours before CABG 1

Additional Medical Management

• Beta-blockers should be initiated to reduce myocardial oxygen demand, targeting heart rate 50-60 beats per minute 5, 2
• Nitroglycerin (sublingual or IV) for ongoing chest pain 5, 2
• ACE inhibitor within 24 hours for patients with diabetes, hypertension, LVEF <40%, or heart failure 1

Post-Revascularization Management

Continue dual antiplatelet therapy (aspirin plus P2Y12 inhibitor) for 12 months after PCI unless excessive bleeding risk exists 1, 2:

• After 12 months, transition to aspirin monotherapy indefinitely 2
• Maintain high-intensity statin therapy long-term 1, 2

Critical Pitfalls to Avoid

• Never administer prasugrel before coronary anatomy is known – this markedly increases bleeding risk if urgent CABG is required 1, 3
• Do not delay dual antiplatelet therapy – both aspirin and a P2Y12 inhibitor should be given immediately on presentation 5, 2
• Never use fibrinolytic therapy in NSTEMI – it is contraindicated and harmful 1, 5
• Do not use aspirin maintenance doses >100 mg when ticagrelor is prescribed, as higher doses diminish ticagrelor efficacy 3
• Always calculate anticoagulant doses on a weight-based basis to avoid under- or overdosing 3
• Check renal function before dosing enoxaparin, eptifibatide, or fondaparinux and apply recommended dose adjustments 2, 3
• When fondaparinux is used and the patient proceeds to PCI, add UFH or enoxaparin to prevent catheter-related thrombosis 2, 3
• Do not postpone invasive strategy beyond the recommended timeframe based on risk stratification, as timely angiography reduces mortality 1, 2