What is the recommended initial management and treatment regimen for a patient with non‑ST‑elevation myocardial infarction?

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

All patients presenting with NSTEMI require immediate dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) combined with parenteral anticoagulation, followed by risk stratification to determine timing of coronary angiography within 2 to 72 hours based on clinical features. 1, 2

Immediate Medical Therapy (Within 10 Minutes of Presentation)

Antiplatelet Therapy

• Aspirin 162–325 mg orally immediately (chewed for faster absorption), then 75–100 mg daily indefinitely. 1, 2
• P2Y12 inhibitor selection:
  • Ticagrelor 180 mg loading dose, then 90 mg twice daily is preferred for all NSTEMI patients due to superior outcomes compared to clopidogrel. 1
  • Prasugrel 60 mg loading dose, then 10 mg daily (reduce to 5 mg daily if age ≥75 years or weight <60 kg) is preferred over clopidogrel but should be given only after coronary anatomy is known and before PCI—not as pretreatment. 1, 2
  • Clopidogrel 300–600 mg loading dose, then 75 mg daily is acceptable if ticagrelor or prasugrel are contraindicated or unavailable. 1, 2
• Continue P2Y12 inhibitor for at least 12 months regardless of whether a stent was placed. 1, 2

Anticoagulation Therapy

• All NSTEMI patients require parenteral anticoagulation in addition to antiplatelet therapy. 1, 3
• Agent selection based on strategy and renal function:
  • Enoxaparin 1 mg/kg subcutaneously every 12 hours is preferred over unfractionated heparin (UFH) for early invasive or conservative strategies, unless CABG is planned within 24 hours or severe renal impairment (CrCl <30 mL/min) is present. 1, 2
  • Unfractionated heparin: 60 U/kg IV bolus (maximum 4,000 U), then 12 U/kg/hour infusion (maximum 1,000 U/hour), targeting aPTT 1.5–2.0 × control (50–70 seconds). Use UFH if severe renal impairment or CABG planned. 1, 4
  • Fondaparinux 2.5 mg subcutaneously daily has the lowest bleeding risk and is preferred for conservative strategy, but must be supplemented with UFH during PCI to prevent catheter thrombosis. 1, 3
  • Bivalirudin is an alternative for patients undergoing PCI with increased bleeding risk. 1

Duration of Anticoagulation

• UFH: Continue for at least 48 hours or until PCI/discharge, whichever comes first. 1
• Enoxaparin or fondaparinux: Continue for duration of hospitalization, up to 8 days. 1
• Discontinue anticoagulation immediately after uncomplicated PCI. 1

Anti-Ischemic Therapy

• Beta-blockers (e.g., metoprolol) should be initiated to reduce myocardial oxygen demand unless contraindicated (heart failure, bradycardia, hypotension). 1, 2
• Nitroglycerin (sublingual 0.4 mg every 5 minutes × 3 doses, then IV infusion) for ongoing chest pain, unless systolic BP <90 mmHg, severe bradycardia/tachycardia, right ventricular infarction, or phosphodiesterase inhibitor use within 24–48 hours. 1, 4
• Morphine sulfate 2–4 mg IV for uncontrolled ischemic chest pain despite nitroglycerin. 1
• Supplemental oxygen only if arterial oxygen saturation <90%. 1

Supportive Care

• Admit to monitored unit with continuous rhythm monitoring for at least 24 hours. 1
• Obtain 12-lead ECG within 10 minutes of presentation. 1

Risk Stratification and Timing of Invasive Strategy

Immediate Invasive Strategy (<2 Hours)

Proceed directly to catheterization laboratory for:

• Refractory or recurrent angina despite optimal medical therapy. 1, 2
• Hemodynamic instability or cardiogenic shock. 1, 2
• Life-threatening arrhythmias (sustained ventricular tachycardia/fibrillation) or cardiac arrest. 1, 2
• Acute heart failure or mechanical complications of MI. 1

Early Invasive Strategy (<24 Hours)

Perform coronary angiography within 24 hours for high-risk patients with:

• Elevated cardiac troponin (troponin T >0.01 ng/mL or troponin I >0.1 ng/mL). 1, 2
• Dynamic ST-segment depression ≥0.5 mm or T-wave changes on ECG. 1, 2
• GRACE risk score >140 or TIMI risk score ≥3. 1, 2
• Diabetes mellitus. 1, 2
• Left ventricular ejection fraction (LVEF) <40%. 2
• Prior PCI or CABG. 2

Standard Invasive Strategy (<72 Hours)

• Intermediate-risk patients who are symptom-stable but meet at least one intermediate-risk criterion (modest biomarker rise, moderate GRACE score). 1

Conservative (Non-Invasive) Strategy

• Low GRACE score with no ongoing ischemia. 1
• Significant comorbidities where procedural risk outweighs benefit. 1
• Patients who will not consent to revascularization. 2

Glycoprotein IIb/IIIa Inhibitors

• Eptifibatide or tirofiban should be used in high-risk NSTEMI patients undergoing PCI, particularly when dual antiplatelet therapy is not on board. 2, 3
• Avoid routine upstream use (before angiography) due to increased bleeding risk without reduction in ischemic events. 1
• Target ACT during PCI: 200 seconds when GP IIb/IIIa inhibitors are used, 250–350 seconds without. 1

Post-Angiography Management

If PCI is Performed

• Continue aspirin indefinitely. 1
• Administer P2Y12 inhibitor loading dose if not given before angiography. 1
• Discontinue anticoagulation immediately after uncomplicated PCI. 1
• Drug-eluting stents are preferred over balloon angioplasty alone. 2

If CABG is Selected

• Continue aspirin through surgery. 1
• Discontinue P2Y12 inhibitors before CABG:
  • Clopidogrel: 5–7 days before. 1
  • Ticagrelor: 5 days before. 1
  • Prasugrel: 7 days before. 1
• Switch enoxaparin, fondaparinux, or bivalirudin to UFH 12–24 hours before CABG. 1

If Medical Therapy is Selected

• Continue aspirin indefinitely. 1
• Administer clopidogrel loading dose if not given before angiography. 1

Long-Term Secondary Prevention

• Measure LVEF in all patients. 1
  • If LVEF ≤0.40: Consider diagnostic angiography if not already performed. 1
  • If LVEF >0.40: Consider stress testing. 1
• ACE inhibitors for patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes. 1, 2
• ARBs for ACE inhibitor-intolerant patients. 1, 2
• High-intensity statin therapy (e.g., atorvastatin 80 mg or rosuvastatin 40 mg daily) regardless of baseline LDL levels. 1, 2
• Beta-blockers continued indefinitely unless contraindicated. 1, 2

Critical Pitfalls to Avoid

• DO NOT administer fibrinolytic therapy—this is absolutely contraindicated in NSTEMI and may increase mortality. 2, 4
• DO NOT use NSAIDs (except aspirin) during hospitalization due to increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture. 1
• DO NOT switch between anticoagulants (e.g., UFH to enoxaparin)—this increases bleeding risk. 1
• DO NOT use fondaparinux as sole anticoagulant during PCI—must add UFH bolus to prevent catheter thrombosis. 1
• DO NOT delay invasive strategy in high-risk patients—the ISAR-COOL trial showed worse outcomes with delayed approach (86 hours) versus very early strategy (2.4 hours). 2
• DO NOT combine clopidogrel with omeprazole or esomeprazole—this significantly reduces antiplatelet efficacy. 2
• DO NOT give immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade. 1
• DO NOT administer IV ACE inhibitors within the first 24 hours due to increased risk of hypotension. 1
• DO NOT dismiss ST depressions as "non-specific" when they occur during symptomatic episodes—they represent high-risk unstable angina requiring aggressive therapy even with negative troponins. 4

Special Populations: NSTEMI with Active Gastrointestinal Bleeding

• Continue low-dose aspirin 81 mg daily unless bleeding is immediately life-threatening—cardiovascular mortality benefit outweighs bleeding risk. 1
• Initiate high-dose IV PPI (80 mg bolus, then 8 mg/hour infusion × 72 hours), then switch to oral PPI indefinitely. 1
• Defer dual antiplatelet therapy until bleeding source is controlled. 1
• Avoid GP IIb/IIIa inhibitors in active bleeding. 1
• Heparin may be justified if ongoing refractory ischemia persists despite optimal anti-ischemic therapy, but should be withheld if ischemia is controlled or bleeding risk exceeds thrombotic risk. 1
• Fondaparinux has lowest bleeding risk among anticoagulants if anticoagulation is deemed necessary. 1