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

Management of NSTEMI

For patients presenting with NSTEMI, immediately administer aspirin 150-300 mg and a P2Y12 inhibitor (preferably ticagrelor 180 mg), initiate parenteral anticoagulation, and proceed to coronary angiography within 24 hours for high-risk patients or within 2 hours if hemodynamically unstable, ongoing ischemia, or life-threatening arrhythmias are present. 1, 2

Initial Assessment and Diagnosis

Immediate Evaluation (Within 10 Minutes)

• Obtain a 12-lead ECG within 10 minutes of first medical contact to differentiate STEMI from NSTE-ACS and identify high-risk features 1, 2
• Measure high-sensitivity cardiac troponin at presentation (0 h) and repeat at 1 hour using validated 0h/1h algorithms, or at 2-3 hours if using conventional assays 1, 2
• Initiate continuous cardiac rhythm monitoring immediately and maintain until NSTEMI is confirmed or ruled out 1
• Assess vital signs including blood pressure, heart rate, oxygen saturation, and perform cardiopulmonary auscultation with Killip classification 1

Diagnostic Criteria

• NSTEMI diagnosis requires: Elevated troponin (≥99th percentile upper reference limit) with a rising or falling pattern (≥20% change between measurements) plus clinical evidence of myocardial ischemia, without persistent ST-segment elevation 1, 2
• High-risk ECG findings include: ST-segment depression ≥0.5 mm in multiple leads, transient ST-elevation that resolves, T-wave inversions >1 mm in leads with dominant R waves, or dynamic ST-T changes during chest pain episodes 2

Additional Diagnostic Testing

• Draw blood for hemoglobin, serum creatinine with eGFR calculation, platelet count, blood glucose, and lipid profile on admission 1, 2
• Perform emergency transthoracic echocardiography to evaluate left ventricular function, regional wall motion abnormalities, right ventricular involvement, valvular disease, and exclude mechanical complications 1, 2
• Results of troponin measurements must be available within 60 minutes 1

Risk Stratification

GRACE Risk Score

• Calculate the GRACE risk score for all patients; a score >140 identifies very high-risk patients requiring early invasive strategy within 24 hours 1, 2, 3
• GRACE score >140 is an independent predictor of 1-year all-cause mortality 3

Very High-Risk Features (Emergency Angiography <2 Hours)

• Hemodynamic instability or cardiogenic shock 1, 2
• Recurrent or ongoing chest pain refractory to optimal medical therapy 1, 2
• Life-threatening ventricular arrhythmias (ventricular tachycardia or fibrillation) 1, 2
• Mechanical complications such as acute severe mitral regurgitation or ventricular septal defect 1, 2
• Acute heart failure syndrome complicating the acute coronary syndrome 1, 2

High-Risk Features (Early Invasive Strategy <24 Hours)

• Elevated troponin confirming NSTEMI 1, 2
• Dynamic ST-segment changes or new contiguous ST-T segment changes indicating ongoing ischemia 1, 2
• Transient ST-segment elevation 1, 2
• GRACE score >140 1, 2
• High-sensitivity troponin >50 ng/L is associated with adjudicated NSTEMI in 61.7% of patients and predicts 1-year mortality 3

Acute Pharmacological Management

Antiplatelet Therapy (Initiate Immediately)

• Aspirin: Loading dose 150-300 mg orally (or 75-250 mg IV if unable to take oral), then maintenance dose 75-100 mg daily indefinitely 1, 2
• P2Y12 inhibitor (choose one based on clinical scenario):
  • Ticagrelor (preferred): 180 mg loading dose, then 90 mg twice daily—recommended irrespective of invasive or conservative strategy 1, 2
  • Prasugrel: 60 mg loading dose, then 10 mg daily (5 mg daily if age ≥75 years or weight <60 kg)—only after coronary anatomy is known and only if proceeding to PCI, contraindicated if prior stroke/TIA 1, 2
  • Clopidogrel: 300-600 mg loading dose, then 75 mg daily—only when ticagrelor or prasugrel are contraindicated, unavailable, or not tolerated 1, 2
• Continue dual antiplatelet therapy (aspirin plus P2Y12 inhibitor) for 12 months unless excessive bleeding risk 1, 2
• Do NOT routinely pre-treat with P2Y12 inhibitors in patients with unknown coronary anatomy when early invasive management is planned 1
• Do NOT use GP IIb/IIIa antagonists routinely in patients with unknown coronary anatomy 1

Anticoagulation (Initiate Immediately)

• Parenteral anticoagulation is mandatory for all NSTEMI patients in addition to antiplatelet therapy 1, 2
• Preferred regimen for conservative strategy: Fondaparinux 2.5 mg subcutaneously once daily (lowest bleeding risk) 1, 2
• Alternative: Enoxaparin 1 mg/kg subcutaneously twice daily, with dose adjustment for renal dysfunction (CrCl <30 mL/min: 1 mg/kg once daily) 1, 2
• Unfractionated heparin: Weight-adjusted IV bolus (60-70 units/kg, maximum 5000 units) followed by infusion (12-15 units/kg/h, maximum 1000 units/h)—indicated when high bleeding risk, severe renal dysfunction (CrCl <30 mL/min), or immediate angiography is planned 1, 2
• Bivalirudin: 0.75 mg/kg IV bolus followed by 1.75 mg/kg/h infusion for up to 4 hours after PCI—recommended as alternative to UFH plus GP IIb/IIIa inhibitors during PCI 1
• Continue anticoagulation until revascularization or hospital discharge 1, 2

Anti-Ischemic Therapy

• Nitrates: Sublingual nitroglycerin 0.4 mg every 5 minutes (up to 3 doses) for ongoing chest pain; if pain persists, initiate IV nitroglycerin infusion starting at 10-20 mcg/min 1, 2
  • Contraindications: Systolic blood pressure <90 mmHg, severe bradycardia, right ventricular infarction, or phosphodiesterase inhibitor use within 24-48 hours 2
• Beta-blockers: Initiate oral beta-blocker within 24 hours in hemodynamically stable patients without heart failure, hypotension (SBP <100 mmHg), bradycardia (HR <60 bpm), or AV block 1, 2
  • Avoid IV beta-blockers acutely due to increased risk of cardiogenic shock 2
• Morphine: 5 mg IV for pain relief if needed, but use cautiously as it may delay absorption of oral P2Y12 inhibitors 1, 2
• Oxygen: Only administer if oxygen saturation <90% or respiratory distress; routine oxygen in non-hypoxemic patients is not recommended 1

High-Intensity Statin Therapy

• Initiate immediately regardless of baseline cholesterol: atorvastatin 80 mg or rosuvastatin 40 mg daily 1, 2

ACE Inhibitor or ARB

• Start within 24 hours in patients with heart failure, left ventricular ejection fraction <40%, diabetes, or anterior MI; continue indefinitely 1, 2
• Use ARB if ACE inhibitor is not tolerated 1

Mineralocorticoid Receptor Antagonist

• Eplerenone is recommended in patients with LVEF ≤35% and either heart failure or diabetes after NSTE-ACS, provided no significant renal dysfunction (CrCl >30 mL/min) or hyperkalemia (K+ <5.0 mEq/L) 1

Invasive Strategy and Timing

Emergency Angiography (<2 Hours from First Medical Contact)

Mandatory for patients with any very high-risk criterion:

• Cardiogenic shock or hemodynamic instability 1, 2
• Severe ongoing ischemia despite optimal medical therapy 1, 2
• Life-threatening ventricular arrhythmias (VT/VF) 1, 2
• Mechanical complications (acute severe MR, VSD, free wall rupture) 1, 2
• Acute heart failure complicating ACS 1, 2

Early Invasive Strategy (<24 Hours)

Recommended for patients with any high-risk criterion:

• Elevated troponin confirming NSTEMI 1, 2
• Dynamic or new contiguous ST-segment changes 1, 2
• Transient ST-segment elevation 1, 2
• GRACE score >140 1, 2
• Most patients respond to initial pharmacological treatment but require early angiography followed by revascularization 1
• Early invasive strategy (within 24 hours) significantly reduces death or non-fatal MI compared to delayed strategy, primarily by preventing early reinfarction 4

Selective Invasive Strategy (24-72 Hours)

• Recommended for intermediate-risk patients with at least one intermediate-risk criterion but no high-risk features 1
• This is the maximal acceptable delay for coronary angiography in patients without recurrence of symptoms 1

Conservative Strategy with Ischemia-Guided Approach

• Reserved for low-risk patients (normal troponin, non-diagnostic ECG, GRACE <140) 2
• Perform non-invasive stress testing (preferably with imaging) or coronary CT angiography before discharge 1, 2
• Proceed to invasive angiography only if ischemia is detected or symptoms recur 1, 2

Revascularization Strategy

Access and Technique

• Radial artery access is the standard approach for coronary angiography and PCI, significantly reducing bleeding complications compared to femoral access 1, 2
• Use drug-eluting stents for all PCI procedures; bare-metal stents should be avoided regardless of anticipated DAPT duration 2

Culprit Lesion and Multivessel Disease

• Treat the culprit lesion first during the index procedure 2
• In stable patients with multivessel disease, complete revascularization may be performed during the index procedure or staged 2
• In cardiogenic shock, limit PCI to the culprit lesion only; immediate multivessel PCI is not recommended 2

Coronary Artery Bypass Grafting Indications

• Left main disease with >50% stenosis 2
• Three-vessel disease 2
• Two-vessel disease with proximal LAD involvement plus either LVEF <50% or demonstrable ischemia 2

Special Populations

Cardiogenic Shock

• Mandatory emergency coronary angiography with PCI of culprit lesion if feasible, or emergency CABG if anatomy not suitable for PCI 2
• Routine intra-aortic balloon pump is not recommended 2
• Short-term mechanical circulatory support (e.g., Impella, ECMO) may be considered on case-by-case basis 2

Elderly Patients (Age ≥75 Years)

• Apply the same diagnostic and invasive strategies as younger patients 2
• Adjust antithrombotic dosing: prasugrel 5 mg daily (instead of 10 mg) if age ≥75 years or weight <60 kg 1, 2
• Dose-adjust anticoagulants based on renal function 2

Chronic Kidney Disease

• Apply standard diagnostic and therapeutic strategies with medication dose adjustments based on creatinine clearance 2
• Use low- or iso-osmolar contrast agents at the lowest feasible volume 2
• Enoxaparin: reduce to 1 mg/kg once daily if CrCl <30 mL/min 2
• Fondaparinux: contraindicated if CrCl <20 mL/min 2

MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries)

• Follow a diagnostic algorithm to exclude alternative diagnoses (coronary spasm, spontaneous coronary artery dissection, thromboembolism, Takotsubo syndrome, myocarditis) 1, 2
• Perform cardiac MRI in all MINOCA patients without an obvious cause 2
• Manage according to disease-specific guidelines once underlying etiology is identified 2

Critical Pitfalls and Contraindications

Absolute Contraindications

• Fibrinolytic therapy is absolutely contraindicated in NSTE-ACS and may cause harm because the pathology involves partial or intermittent coronary occlusion rather than complete thrombotic occlusion 2

Common Pitfalls to Avoid

• Do not delay angiography beyond 24 hours in high-risk patients, as this increases early reinfarction risk 4
• Do not routinely administer GP IIb/IIIa inhibitors before coronary anatomy is known 1
• Do not give IV beta-blockers acutely due to shock risk; use oral formulation after stabilization 2
• Do not use prasugrel in patients with prior stroke/TIA or before coronary anatomy is known 1, 2
• Do not administer oxygen routinely to non-hypoxemic patients 1
• Avoid morphine if possible as it delays P2Y12 inhibitor absorption 1
• Do not perform immediate multivessel PCI in cardiogenic shock; treat culprit lesion only 2

Monitoring and Disposition

Continuous Monitoring

• Admit all NSTEMI patients to a monitored unit (CCU or step-down unit) 1
• Continue rhythm monitoring for at least 24 hours or until PCI (whichever comes first) in low-risk patients 1
• Extend rhythm monitoring beyond 24 hours in patients at increased risk for cardiac arrhythmias (LVEF <40%, heart failure, hemodynamic instability, complex ventricular arrhythmias) 1

Secondary Prevention at Discharge

• Continue aspirin 75-100 mg daily indefinitely 1, 2
• Continue P2Y12 inhibitor for 12 months (may extend beyond 1 year after careful ischemic/bleeding risk assessment) 1, 2
• Continue high-intensity statin therapy 1, 2
• Continue beta-blocker in patients with LVEF ≤40% 1
• Continue ACE inhibitor or ARB in patients with LVEF ≤40%, heart failure, hypertension, or diabetes 1
• Target diastolic blood pressure <90 mmHg (<85 mmHg in diabetic patients) 1
• Provide smoking cessation counseling and enroll in cardiac rehabilitation program 1