What is the recommended management of non‑ST‑elevation myocardial infarction (NSTEMI)?

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

All NSTEMI patients require immediate aspirin (162-325 mg loading dose, then 75-100 mg daily indefinitely), dual antiplatelet therapy with a P2Y12 inhibitor for at least 12 months, parenteral anticoagulation, and risk-stratified invasive management within 2-72 hours based on clinical features. 1

Immediate Initial Management (First 10 Minutes)

• Obtain a 12-lead ECG within 10 minutes of first medical contact and interpret it immediately to confirm NSTEMI (absence of persistent ST-elevation but elevated cardiac troponin). 1
• Administer aspirin 162-325 mg (chewable, non-enteric-coated) immediately, followed by maintenance dosing of 75-100 mg daily indefinitely. 1, 2
• Admit the patient to a monitored unit with continuous rhythm monitoring for at least 24 hours (longer if increased arrhythmia risk). 1
• Administer supplemental oxygen only if arterial oxygen saturation is <90%. 1
• Give sublingual or intravenous nitroglycerin for ongoing ischemic chest pain unless systolic blood pressure <90 mmHg, severe bradycardia or tachycardia, right ventricular infarction, or recent phosphodiesterase inhibitor use within 24-48 hours. 1
• Initiate beta-blocker therapy to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility. 2

Antiplatelet Therapy Strategy

Ticagrelor is the preferred P2Y12 inhibitor for all NSTEMI patients, regardless of whether an invasive or conservative strategy is planned. 1, 2

• Administer ticagrelor 180 mg loading dose, then 90 mg twice daily. 1, 2
• Prasugrel (60 mg loading dose, then 10 mg daily; reduce to 5 mg daily if age ≥75 years or weight <60 kg) should be considered for patients proceeding to PCI, but only after coronary anatomy has been defined to avoid use in patients with prior stroke/TIA (absolute contraindication). 1, 2
• Clopidogrel (300-600 mg loading dose, then 75 mg daily) is reserved only when prasugrel or ticagrelor are unavailable, contraindicated, or not tolerated. 1, 2
• Continue P2Y12 inhibitor for at least 12 months after NSTEMI, regardless of whether a stent was placed. 1, 2
• Do not routinely pre-treat with a P2Y12 inhibitor when coronary anatomy is unknown and an early invasive strategy is planned, to preserve the option of prasugrel and avoid unnecessary bleeding. 1, 2

Anticoagulation Strategy

All NSTEMI patients require immediate parenteral anticoagulation in addition to dual antiplatelet therapy, regardless of whether an invasive or conservative approach is planned. 1, 2

Agent Selection Based on Renal Function and Strategy

• Normal to mild renal impairment (CrCl >30 mL/min): Enoxaparin 1 mg/kg subcutaneously every 12 hours is preferred. 1, 2
• Moderate renal impairment: Enoxaparin requires dose adjustment; bivalirudin or UFH may be considered as they do not require renal dose adjustment. 2
• Severe renal impairment or end-stage renal disease (CrCl <30 mL/min): UFH is preferred as it does not accumulate with renal dysfunction. 2
• Conservative strategy: Fondaparinux is preferred due to lower bleeding risk. 2
• Early invasive strategy: Unfractionated heparin or enoxaparin. 2

Dosing and Duration

• UFH: Initial bolus of 60 U/kg (maximum 4,000 U) followed by continuous infusion of 12 U/kg/h (maximum 1,000 U/h); target aPTT 1.5-2.0 × control (≈50-70 seconds). Continue for at least 48 hours or until PCI is performed. 1, 2
• Enoxaparin: 1 mg/kg subcutaneously every 12 hours. Continue for the duration of hospitalization, up to 8 days. 1, 2
• Fondaparinux: Continue for the duration of hospitalization, up to 8 days. 1, 2

Critical Anticoagulation Pitfalls

• Do not switch between anticoagulants as this increases bleeding risk. 2
• Do not use fondaparinux as the sole anticoagulant during PCI—it must be supplemented with UFH due to risk of catheter thrombosis. 2

Risk Stratification and Timing of Invasive Strategy

Immediate Invasive Strategy (<2 Hours)

Indicated for very high-risk patients with any of the following: 1, 2

• Refractory or recurrent angina despite optimal medical therapy
• Hemodynamic instability or cardiogenic shock
• Life-threatening arrhythmias or cardiac arrest
• Acute heart failure

Early Invasive Strategy (<24 Hours)

Indicated for high-risk patients with any of the following: 1, 2

• Elevated cardiac troponin with high-risk features
• Dynamic ST-segment or T-wave changes
• High GRACE or TIMI risk score
• Diabetes mellitus

Standard Invasive Strategy (<72 Hours)

• Applied to intermediate-risk patients who are symptom-stable but meet at least one intermediate-risk criterion (e.g., modest biomarker rise, moderate GRACE score). 2

Conservative (Non-Invasive) Strategy

• Suitable for patients with a low GRACE score and no ongoing ischemia. 2
• Also appropriate for patients with significant comorbidities where procedural risk outweighs potential benefit. 2
• Perform stress testing after 24-48 hours of clinical stability to assess for inducible ischemia. 1

Glycoprotein IIb/IIIa Inhibitor Use

Glycoprotein IIb/IIIa inhibitors should not be used routinely or upstream; they are reserved for bail-out situations such as no-reflow or thrombotic complications during PCI. 1, 2

• Treatment with GP IIb/IIIa antagonists in patients in whom coronary anatomy is not known is not recommended. 1

Post-Angiography Management

If PCI is Selected

• Continue aspirin indefinitely. 1, 2
• Administer a loading dose of P2Y12 inhibitor if not started before diagnostic angiography. 1, 2
• Discontinue anticoagulant therapy after PCI for uncomplicated cases. 1, 2

If CABG is Selected

• Continue aspirin indefinitely. 1, 2
• Discontinue clopidogrel 5-7 days before elective CABG. 1, 2
• Discontinue ticagrelor 5 days before elective CABG. 2
• Discontinue prasugrel at least 7 days before CABG. 2
• Discontinue IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban) 4 hours before CABG. 1
• Continue UFH through CABG. 1, 2
• Discontinue enoxaparin 12-24 hours before CABG and switch to UFH. 1, 2
• Discontinue fondaparinux 24 hours before CABG and switch to UFH. 1, 2
• Discontinue bivalirudin 3 hours before CABG and switch to UFH. 1, 2

If Medical Therapy is Selected

• Continue aspirin indefinitely. 1
• Administer a loading dose of clopidogrel if not given before diagnostic angiography. 1
• Continue UFH for at least 48 hours or discontinue enoxaparin or fondaparinux for duration of hospitalization. 1

Long-Term Secondary Prevention

• Measure left ventricular ejection fraction (LVEF) in all patients. 2
• If LVEF ≤0.40, consider diagnostic angiography. 2
• If LVEF >0.40, consider a stress test. 2
• Initiate ACE inhibitors for patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes. 2
• Consider ARBs for ACE inhibitor-intolerant patients. 2
• Initiate high-intensity statin therapy (e.g., atorvastatin 80 mg daily) regardless of baseline LDL levels. 2
• Continue beta-blockers as mandatory long-term therapy. 2

Special Considerations: NSTEMI with Active Gastrointestinal Bleeding

• Continue low-dose aspirin 81 mg daily unless the bleeding is immediately life-threatening; the cardiovascular mortality benefit outweighs bleeding risk. 2
• Initiate high-dose intravenous PPI immediately (80 mg bolus followed by continuous infusion of 8 mg/h for 72 hours), then switch to standard once-daily oral PPI indefinitely. 2
• Defer dual antiplatelet therapy until the bleeding source is controlled. 2
• Glycoprotein IIb/IIIa inhibitors should not be administered in the setting of active gastrointestinal bleeding. 2
• Heparin may be justified when ongoing refractory ischemia persists despite optimal anti-ischemic therapy, indicating a high thrombotic risk that outweighs bleeding concerns. 2
• If the bleeding risk exceeds the thrombotic risk, a conservative strategy without any anticoagulant is recommended. 2

Critical Pitfalls to Avoid

• Avoid NSAIDs (except aspirin) during hospitalization due to increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture. 2
• Do not administer immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade. 2
• Avoid intravenous ACE inhibitors within the first 24 hours due to increased risk of hypotension. 2
• Do not abruptly discontinue antiplatelet therapy, especially in patients who have undergone PCI, as this increases risk of stent thrombosis and recurrent events. 3
• Never use fibrinolytic therapy in NSTEMI without ST-segment elevation. 1, 4