How should a patient with non‑ST‑segment elevation myocardial infarction (NSTEMI) be treated?

Treatment of NSTEMI

All patients with NSTEMI should receive immediate aspirin 162-325 mg, dual antiplatelet therapy with a P2Y12 inhibitor (preferably ticagrelor or prasugrel over clopidogrel), parenteral anticoagulation, and undergo risk stratification to determine timing of invasive coronary angiography within 2 to 72 hours based on clinical risk features. 1, 2, 3

Immediate Management (First 10 Minutes)

• Obtain a 12-lead ECG within 10 minutes of first medical contact and have it interpreted immediately to distinguish NSTEMI from STEMI 4, 3
• Administer aspirin 162-325 mg orally immediately upon presentation, followed by 75-162 mg daily indefinitely 1, 2, 3
• Admit to a monitored unit with continuous rhythm monitoring for at least 24 hours 1, 2
• Administer supplemental oxygen only if arterial oxygen saturation is <90% 1, 2
• Measure high-sensitivity cardiac troponin at presentation (0 h) and again at 1 hour using the ESC 0h/1h algorithm for rapid diagnosis 3

Anti-Ischemic Therapy

• Administer sublingual or intravenous nitroglycerin for ongoing chest pain unless contraindicated (systolic BP <90 mmHg, severe bradycardia, tachycardia without heart failure, right ventricular infarction, or recent phosphodiesterase inhibitor use within 24-48 hours) 1, 2
• Initiate beta-blockers to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and myocardial contractility 1, 2
• Consider morphine sulfate intravenously for uncontrolled ischemic chest discomfort despite nitroglycerin 2

Antiplatelet Therapy

Initial P2Y12 Inhibitor Selection

• Ticagrelor is the preferred P2Y12 inhibitor with a loading dose of 180 mg followed by 90 mg twice daily, regardless of planned invasive or conservative strategy 1, 3
• Prasugrel (loading dose 60 mg, maintenance 10 mg daily; 5 mg daily if ≥75 years or weight <60 kg) is recommended only after coronary angiography and prior to PCI in P2Y12-naive patients 4, 3
• Clopidogrel (loading dose 300-600 mg, maintenance 75 mg daily) should be used only when ticagrelor or prasugrel are unavailable, not tolerated, or contraindicated 3, 5
• Avoid clopidogrel in CYP2C19 poor metabolizers—consider genetic testing and use ticagrelor or prasugrel instead 5

Duration and Special Considerations

• Continue P2Y12 inhibitor for at least 12 months after NSTEMI, regardless of whether a stent was placed 1, 2
• If CABG is planned, discontinue clopidogrel 5-7 days before surgery, prasugrel at least 7 days before, and ticagrelor at least 5 days before 2, 3
• Continue aspirin throughout the perioperative period 2, 3

Anticoagulation Strategy

Agent Selection Based on Strategy and Renal Function

• All NSTEMI patients require parenteral anticoagulation in addition to antiplatelet therapy 1, 2, 3

For Early Invasive Strategy (angiography within 24-48 hours):

• Unfractionated heparin (UFH): bolus 60 U/kg (maximum 4,000 U) followed by infusion 12 U/kg/h (maximum 1,000 U/h), target aPTT 1.5-2.0 × control (50-70 seconds) 2
• Enoxaparin: 1 mg/kg subcutaneously every 12 hours (maximum 10,000 IU twice daily) if creatinine clearance ≥30 mL/min 2, 3
• Bivalirudin: 0.75 mg/kg IV bolus, then 1.75 mg/kg/h infusion as an alternative to UFH plus GP IIb/IIIa inhibitors during PCI 3

For Conservative Strategy:

• Fondaparinux is preferred due to lowest bleeding risk: 2.5 mg subcutaneously once daily 2, 3

For Severe Renal Impairment (CrCl <30 mL/min):

• UFH is preferred as it does not accumulate with renal dysfunction 2

Duration of Anticoagulation

• Continue UFH for at least 48 hours or until discharge if given before angiography 2, 3
• Continue enoxaparin or fondaparinux for the duration of hospitalization, up to 8 days, if given before angiography 2, 3
• Discontinue anticoagulation immediately after uncomplicated PCI 2, 3
• Do not switch between anticoagulants as this increases bleeding risk 2

Critical Anticoagulation Pitfall

• If fondaparinux is used, add UFH during PCI to prevent catheter thrombosis—fondaparinux alone is insufficient 2

Risk Stratification and Timing of Invasive Strategy

Apply GRACE Risk Score for Prognostic Assessment 3

Immediate Invasive Strategy (<2 hours):

• Refractory or recurrent angina despite medical therapy 4, 2, 3
• Hemodynamic instability or cardiogenic shock 4, 2, 3
• Life-threatening arrhythmias or cardiac arrest 4, 2, 3
• Acute heart failure 2
• Mechanical complications of MI 3

Early Invasive Strategy (<24 hours):

• Elevated cardiac biomarkers (troponin) with high-risk features 4, 2, 3
• Dynamic ST-segment or T-wave changes 2, 3
• High GRACE or TIMI risk score 1, 2, 3
• Diabetes mellitus 2

Invasive Strategy (<72 hours):

• Intermediate-risk patients without recurrence of symptoms but with at least one intermediate-risk criterion 4

Conservative Strategy:

• Low GRACE score without ongoing ischemia 4, 3
• Significant comorbidities where risks of invasive approach outweigh benefits 4, 3

Glycoprotein IIb/IIIa Inhibitors

• Do not use GP IIb/IIIa inhibitors routinely upstream before angiography—they increase major bleeding (2.6% vs 1.8%; p=0.02) without reducing ischemic events 3
• Consider eptifibatide or tirofiban only for moderate- to high-risk patients with refractory ischemia during PCI 1, 6, 7
• Never administer GP IIb/IIIa inhibitors in patients with active bleeding 2

Post-Angiography Management

After PCI

• Continue aspirin indefinitely 2, 3
• Administer P2Y12 inhibitor loading dose if not given before angiography 2, 3
• Discontinue anticoagulation after uncomplicated PCI 2, 3

After CABG

• Continue aspirin throughout perioperative period 2, 3
• Discontinue clopidogrel 5-7 days before surgery 2, 3
• Stop bivalirudin 3 hours before CABG and substitute UFH 3
• Stop enoxaparin 12-24 hours before CABG and switch to UFH 2
• Stop fondaparinux 24 hours before CABG and switch to UFH 2

Medical Management (No Revascularization)

• Continue aspirin indefinitely 2, 3
• Administer P2Y12 inhibitor loading dose if not given before angiography 2, 3
• Continue anticoagulation for duration specified above 2, 3

Long-Term Secondary Prevention

• Measure left ventricular ejection fraction (LVEF) in all patients 1, 2, 3
• If LVEF ≤0.40, consider diagnostic angiography 1, 2
• Initiate high-intensity statin therapy in all NSTEMI patients regardless of baseline LDL levels 2, 3
• 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
• Initiate beta-blockers for all NSTEMI patients without contraindications 3

Common Pitfalls and Contraindications

• Avoid NSAIDs (except aspirin) during hospitalization—they increase mortality, reinfarction, hypertension, heart failure, and myocardial rupture 1, 2
• Do not administer immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 1, 2
• Avoid intravenous ACE inhibitors within the first 24 hours due to increased risk of hypotension 2
• Avoid concomitant use of clopidogrel with omeprazole or esomeprazole—they significantly reduce clopidogrel's antiplatelet activity 5
• Do not give platelet transfusions within 4 hours of clopidogrel loading dose or 2 hours of maintenance dose—they may be ineffective 5