What is the recommended immediate management for a patient presenting with a non‑ST‑elevation myocardial infarction (NSTEMI)?

Immediate Management of NSTEMI

For a patient presenting with NSTEMI, immediately administer aspirin 150–300 mg (non-enteric coated) plus a P2Y12 inhibitor (preferably ticagrelor 180 mg loading dose), initiate anticoagulation (fondaparinux preferred), start high-intensity statin therapy, and perform risk stratification to determine timing of coronary angiography—within 2 hours for very high-risk features or within 24 hours for high-risk features. 1, 2

Immediate Pharmacologic Therapy (Within Minutes of Diagnosis)

Antiplatelet Therapy

• Aspirin 150–300 mg loading dose (non-enteric coated) followed by 75–100 mg daily should be administered immediately to all NSTEMI patients 1, 2
• Ticagrelor 180 mg loading dose then 90 mg twice daily is the preferred P2Y12 inhibitor for all moderate-to-high-risk NSTEMI patients, regardless of whether an invasive or conservative strategy is planned 1, 2
• Prasugrel 60 mg loading then 10 mg daily may be used only after coronary anatomy is known and PCI is planned; it is contraindicated in patients with prior stroke/TIA, age ≥75 years, or weight <60 kg 1, 2
• Clopidogrel 300–600 mg loading then 75 mg daily is reserved for patients who cannot receive ticagrelor or prasugrel, or who require oral anticoagulation 1, 2

Anticoagulation

• Fondaparinux is the preferred anticoagulant for medically managed NSTEMI patients due to lower bleeding risk 1, 2
• Enoxaparin (low-molecular-weight heparin) is an acceptable alternative when fondaparinux is unavailable 2
• Unfractionated heparin should be used when PCI is planned within hours or in patients with renal dysfunction (eGFR <30 mL/min/1.73 m²) 1, 2

Additional Immediate Therapies

• High-intensity statin therapy (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) should be started immediately 2
• Nitroglycerin (sublingual 0.4 mg every 5 minutes up to 3 doses, or intravenous infusion) for ongoing chest pain 2
• Morphine 2–4 mg intravenous may be used for refractory pain, but clinicians must recognize it delays absorption of oral P2Y12 inhibitors and should be used sparingly 1, 2
• Supplemental oxygen only if oxygen saturation <90% or respiratory distress—routine oxygen is not beneficial 1, 2
• Oral beta-blocker within 24 hours unless contraindicated by heart failure, hypotension (systolic BP <100 mmHg), bradycardia (HR <60 bpm), or high-degree AV block 2

Risk Stratification and Timing of Invasive Strategy

Very High-Risk: Immediate Angiography (<2 Hours)

Proceed to coronary angiography within 2 hours if any of the following are present: 1, 2

• Hemodynamic instability or cardiogenic shock
• Recurrent or refractory chest pain despite optimal medical therapy
• Life-threatening arrhythmias (sustained ventricular tachycardia or ventricular fibrillation)
• Mechanical complications of MI (acute mitral regurgitation, ventricular septal defect, free wall rupture)
• Acute heart failure clearly related to ongoing ischemia
• ST-segment depression ≥1 mm in ≥6 leads plus ST-elevation in aVR and/or V1

High-Risk: Early Angiography (<24 Hours)

Perform coronary angiography within 24 hours if any of the following are present: 1, 2, 3

• Confirmed NSTEMI diagnosis (rise and/or fall in high-sensitivity troponin with at least one value above the 99th percentile)
• Dynamic or presumably new ST-segment or T-wave changes suggesting ongoing ischemia
• Transient ST-segment elevation
• GRACE risk score >140 1, 2, 3

Intermediate-Risk: Angiography Within 72 Hours

Consider coronary angiography within 72 hours for patients with: 1

• Diabetes mellitus
• Renal insufficiency (eGFR <60 mL/min/1.73 m²)
• Left ventricular ejection fraction <40%
• GRACE score 109–140
• Prior PCI or CABG

Low-Risk: Selective Invasive Strategy

Perform ischemia testing or coronary CT angiography before deciding on invasive management in patients with: 1

• GRACE score <109
• No recurrent ischemia
• No high-risk features on ECG or biomarkers

Cardiac Biomarker Testing

• High-sensitivity cardiac troponin (hs-cTn) on arrival with results within 60 minutes is the standard of care 2
• 0-hour/1-hour algorithm for rapid rule-in/rule-out when hs-cTn assay is available 2
• 0-hour/2-hour algorithm is acceptable when 1-hour protocol is not feasible 2
• 0-hour/3–6-hour protocol if only conventional troponin assay is available 2

Periprocedural Management for Patients Proceeding to PCI

Antiplatelet Adjustments

• Continue aspirin throughout the procedure 1
• Administer P2Y12 inhibitor loading dose if not given before angiography 1
• GP IIb/IIIa inhibitor (eptifibatide, tirofiban, or abciximab) should be added in troponin-positive high-risk patients undergoing PCI 1, 2
• GP IIb/IIIa inhibitor may be omitted if bivalirudin was used and clopidogrel ≥300 mg was given ≥6 hours earlier 1

Anticoagulation Management

• Discontinue anticoagulation after uncomplicated PCI 1
• If CABG is planned: stop clopidogrel 5–7 days before surgery, stop GP IIb/IIIa inhibitors ≥4 hours before, stop enoxaparin 12–24 hours before, stop fondaparinux 24 hours before, and stop bivalirudin 3 hours before 1

Revascularization Strategy Selection

Indications for PCI

• Single-vessel or two-vessel disease with suitable anatomy 1
• Multivessel disease with normal LV function and no diabetes 1
• Focal saphenous vein graft lesions in poor surgical candidates 1

Indications for CABG

• Three-vessel disease (survival benefit greater with LV ejection fraction <50%) 1
• Two-vessel disease with significant proximal LAD stenosis and either LV ejection fraction <50% or demonstrable ischemia 1
• Left main disease >50% stenosis 4
• Multivessel disease with diabetes mellitus (preferably with internal mammary artery grafting) 1

Contraindications to Early Invasive Strategy

Do not perform early invasive strategy in: 1, 3

• Extensive comorbidities where procedural risks outweigh benefits (severe liver or pulmonary failure, active malignancy)
• Patients who refuse revascularization regardless of findings
• Terminal illness with limited life expectancy
• Low likelihood of ACS after comprehensive evaluation

Long-Term Secondary Prevention

• Dual antiplatelet therapy (aspirin + P2Y12 inhibitor) for 12 months after NSTEMI; shorter duration (3–6 months) may be considered in high bleeding risk 1, 2
• High-intensity statin therapy indefinitely 2
• ACE inhibitor (or ARB if intolerant) for patients with LV ejection fraction ≤40%, heart failure, hypertension, or diabetes 2
• Beta-blocker for patients with LV ejection fraction ≤40% 2
• Mineralocorticoid receptor antagonist (eplerenone preferred) for patients with LV ejection fraction ≤35% and heart failure or diabetes, if no significant renal dysfunction or hyperkalemia 2

Critical Pitfalls to Avoid

• Do not delay angiography in very high-risk patients while waiting for "stabilization"—hemodynamic instability or refractory ischemia mandates immediate catheterization 1, 2
• Do not administer prasugrel before coronary anatomy is known, as it must be stopped 7 days before CABG and increases bleeding risk 1, 2
• Do not use routine morphine liberally, as it delays P2Y12 inhibitor absorption and may compromise antiplatelet efficacy 1, 2
• Do not give fibrinolytic therapy to NSTEMI patients—it is contraindicated and increases risk of MI 1
• Do not withhold upstream antiplatelet therapy until after angiography; aspirin and P2Y12 inhibitor should be given immediately upon diagnosis 2, 4
• Do not routinely administer supplemental oxygen unless oxygen saturation <90% or respiratory distress is present 1, 2