What is the treatment for Non-ST-Elevation Myocardial Infarction (NSTEMI)?

Treatment for NSTEMI

Immediately administer aspirin 162-325 mg (non-enteric, chewed or oral), initiate dual antiplatelet therapy with a P2Y12 inhibitor (preferably ticagrelor), add parenteral anticoagulation, and pursue early invasive strategy with angiography within 24-48 hours for high-risk patients. 1, 2, 3

Immediate Initial Management (First Hours)

• Administer aspirin 162-325 mg immediately as a non-enteric formulation, either chewed or taken orally, regardless of prior aspirin use 1, 2, 3
• Admit to a monitored unit with continuous cardiac rhythm monitoring for at least 24 hours to detect arrhythmias 1, 2, 3
• Provide supplemental oxygen only if arterial oxygen saturation is <90%—routine oxygen administration is not indicated 1, 2, 3
• Administer sublingual or intravenous nitroglycerin for ongoing ischemic chest pain, but avoid if:
  • Systolic blood pressure <90 mmHg or ≥30 mmHg below baseline
  • Severe bradycardia (<50 bpm) or tachycardia (>100 bpm without heart failure)
  • Right ventricular infarction
  • Phosphodiesterase inhibitor use within 24 hours (sildenafil) or 48 hours (tadalafil) 1, 3
• Consider morphine sulfate intravenously for uncontrolled ischemic chest discomfort despite nitroglycerin 2
• Initiate oral beta-blocker therapy (preferred over intravenous) to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility, unless contraindications exist 1, 2, 3

Antiplatelet Therapy Strategy

Aspirin

• Continue aspirin 75-162 mg daily indefinitely after the initial loading dose 1, 2, 3

P2Y12 Inhibitor Selection

• Add a P2Y12 receptor inhibitor to aspirin for 12 months unless contraindicated or high bleeding risk 1, 2
• Ticagrelor is the preferred agent over clopidogrel, with a loading dose of 180 mg, then 90 mg twice daily—recommended regardless of invasive or conservative strategy 4, 1, 2, 3
• If ticagrelor is unavailable or contraindicated, administer clopidogrel with a loading dose:
  • 300-600 mg loading dose if early conservative strategy is selected or if PCI is planned and not started before diagnostic angiography 2, 3
  • Note: Clopidogrel effectiveness is reduced in CYP2C19 poor metabolizers; consider alternative P2Y12 inhibitor in these patients 5
• The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily 4

Anticoagulant Therapy

• Administer parenteral anticoagulation to all NSTEMI patients in addition to antiplatelet therapy, irrespective of initial treatment strategy 4, 1, 2, 3

Anticoagulant Options (Choose One):

• Enoxaparin: 1 mg/kg subcutaneous every 12 hours (reduce to 1 mg/kg once daily if creatinine clearance <30 mL/min), continued for duration of hospitalization or until PCI is performed 4, 2, 3
• Unfractionated heparin (UFH): Initial loading dose of 60 IU/kg (maximum 4000 IU) with initial infusion of 12 IU/kg per hour (maximum 1000 IU/h) adjusted per aPTT, continued for at least 48 hours or until PCI is performed 4, 1, 2, 3
• Bivalirudin: 0.10 mg/kg loading dose followed by 0.25 mg/kg per hour (only in patients managed with early invasive strategy), continued until diagnostic angiography or PCI 4, 2
• Fondaparinux: 2.5 mg subcutaneous daily, continued for duration of hospitalization or until PCI is performed 4, 2, 3
  • If PCI is performed while on fondaparinux, administer additional anticoagulant with anti-IIa activity (either UFH or bivalirudin) because of catheter thrombosis risk 4, 2

Risk Stratification and Management Strategy Selection

Early Invasive Strategy (Angiography Within 24-48 Hours)

Indicated for high-risk patients with:

• Refractory angina or recurrent symptoms 1, 2, 3
• Hemodynamic instability 1, 2, 3
• Electrical instability (life-threatening arrhythmias) 1, 2, 3
• Elevated cardiac biomarkers (positive troponin) 4, 1, 2, 3
• High GRACE or TIMI risk score 1, 2, 3

Conservative (Ischemia-Guided) Strategy

• Appropriate for lower-risk patients without ongoing ischemia or patients with significant comorbidities where invasive risks outweigh benefits 2, 3

Post-Angiography Management

If PCI is Selected:

• Continue aspirin indefinitely 2, 3
• Administer P2Y12 inhibitor loading dose if not started before diagnostic angiography 2, 3

If CABG is Selected:

• Continue aspirin 2, 3
• Discontinue clopidogrel 5-7 days before elective CABG 2, 3
• Ticagrelor and prasugrel also require discontinuation before surgery 2

If Medical Therapy is Selected:

• Continue aspirin 2, 3
• Administer P2Y12 inhibitor loading dose if not given before diagnostic angiography 2, 3

Long-Term Management and Secondary Prevention

• Measure left ventricular ejection fraction (LVEF) in all patients 1, 2, 3
• If LVEF ≤0.40, consider diagnostic angiography 1, 2, 3
• If LVEF >0.40, consider stress testing 2
• Initiate ACE inhibitors for patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes 1, 2, 3
• Consider ARBs for ACE inhibitor-intolerant patients 1, 2, 3
• Continue beta-blockers indefinitely in all NSTEMI patients without contraindications 3
• Initiate high-intensity statin therapy regardless of baseline LDL levels 2, 3
• Continue P2Y12 inhibitor for at least 12 months after NSTEMI, regardless of whether a stent was placed 2

Critical Contraindications and Pitfalls

Absolute Contraindications:

• Intravenous fibrinolytic therapy is contraindicated in NSTEMI patients (without ST-elevation, true posterior MI, or new left bundle-branch block) 4, 3

Important Avoidances:

• Do not administer NSAIDs (except aspirin) during hospitalization due to increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture 1, 2, 3
• Do not give immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 1, 2, 3
• Avoid intravenous ACE inhibitors within the first 24 hours due to hypotension risk (exception: refractory hypertension) 2, 3
• Do not administer intravenous beta blockers to patients with signs of heart failure, low-output state, or cardiogenic shock risk factors 3
• Avoid concomitant use of clopidogrel with omeprazole or esomeprazole because both significantly reduce the antiplatelet activity of clopidogrel 5

Timing Considerations:

• Platelet transfusions may be less effective if given within 4 hours of the loading dose or 2 hours of the maintenance dose of clopidogrel 5
• The immediate invasive strategy (<2 hours) reduces death or new MI compared to delayed intervention (2-72 hours), mainly by preventing pre-catheterization MI 6