What are the guidelines for managing Non-ST-Elevation Myocardial Infarction (NSTEMI)?

NSTEMI Management Guidelines

Administer aspirin 162-325 mg immediately (chewed or non-enteric formulation), admit to a monitored unit with continuous rhythm monitoring, initiate dual antiplatelet therapy with ticagrelor (preferred) or prasugrel, add parenteral anticoagulation, and perform risk stratification to determine timing of invasive coronary angiography within 24-48 hours for high-risk patients. 1, 2

Immediate Initial Management

Aspirin and Monitoring:

• Give aspirin 162-325 mg immediately as a non-enteric formulation (chewed or oral), regardless of prior aspirin use 1
• Continue aspirin 75-100 mg daily indefinitely 3, 1
• Admit all patients to a monitored unit with continuous cardiac rhythm monitoring for at least 24 hours to detect arrhythmias 3, 1

Symptom Management:

• Administer sublingual or intravenous nitroglycerin for ongoing ischemic chest pain, but avoid if systolic BP <90 mmHg or ≥30 mmHg below baseline, severe bradycardia (<50 bpm) or tachycardia (>100 bpm without heart failure), right ventricular infarction, or recent phosphodiesterase inhibitor use (sildenafil within 24 hours, tadalafil within 48 hours) 1
• Consider morphine sulfate intravenously for uncontrolled ischemic chest discomfort despite nitroglycerin 2
• Provide supplemental oxygen only if arterial oxygen saturation is <90%; routine oxygen is not indicated 1, 2

Beta-Blocker Therapy:

• Initiate oral beta-blocker therapy (preferred over intravenous) to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility, unless contraindications exist 1
• Do not administer intravenous beta-blockers to patients with signs of heart failure, low-output state, or cardiogenic shock risk factors 1

Diagnostic Evaluation

ECG and Cardiac Biomarkers:

• Perform 12-lead ECG within 10 minutes of first medical contact with immediate interpretation by an experienced physician 4
• Obtain additional ECG leads (V3R, V4R, V7-V9) if ongoing ischemia is suspected when standard leads are inconclusive 3
• Measure high-sensitivity cardiac troponin (hs-cTn) at 0 hours and 1 hour (ESC 0h/1h algorithm) for diagnosis and prognosis 3, 4
• If the first two troponin measurements are not conclusive and clinical presentation still suggests ACS, perform additional testing after 3 hours 3, 4

Imaging:

• Perform echocardiography to evaluate left ventricular regional and global function and rule out differential diagnoses 3, 4
• In patients with cardiac arrest or hemodynamic instability of presumed cardiovascular origin, perform echocardiography immediately following 12-lead ECG 3

Dual Antiplatelet Therapy (DAPT)

P2Y12 Inhibitor Selection:

• Add a P2Y12 receptor inhibitor to aspirin and maintain for 12 months unless contraindicated or excessive bleeding risk 3, 1
• Ticagrelor is the preferred agent (loading dose 180 mg, then 90 mg twice daily), recommended regardless of invasive or conservative strategy 3, 1, 4
• Prasugrel (loading dose 60 mg, maintenance 10 mg daily; 5 mg daily for patients ≥75 years or weight <60 kg) is recommended for P2Y12 inhibitor-naïve patients proceeding to PCI 3, 4, 5
• Clopidogrel (loading dose 300-600 mg, maintenance 75 mg daily) only when prasugrel or ticagrelor are unavailable, not tolerated, or contraindicated 3, 4

Critical Timing Consideration:

• Do not routinely pre-treat with P2Y12 inhibitors before coronary anatomy is known if early invasive management is planned 3
• In UA/NSTEMI patients, the loading dose should not be administered until coronary anatomy is established 5
• In a trial of 4,033 NSTEMI patients, no clear benefit was observed when prasugrel loading dose was given prior to diagnostic angiography compared to at time of PCI, but bleeding risk increased with early administration 5

Contraindications and Special Populations:

• Prasugrel is contraindicated in patients with prior TIA or stroke (6.5% stroke rate vs. 1.2% with clopidogrel in patients with prior TIA/stroke history) 5
• In patients ≥75 years, prasugrel is generally not recommended except in high-risk situations (diabetes or prior MI) 5
• Consider lowering prasugrel maintenance dose to 5 mg in patients <60 kg due to increased bleeding risk 5

Anticoagulation Therapy

Parenteral Anticoagulation:

• Administer parenteral anticoagulation to all NSTEMI patients in addition to antiplatelet therapy 3, 1, 4
• Options include unfractionated heparin (UFH), enoxaparin, fondaparinux, or bivalirudin 1, 2, 4

Duration of Therapy:

• For medically managed patients, continue intravenous UFH for at least 48 hours or until discharge if given before angiography 1, 2, 4
• Continue enoxaparin for the duration of hospitalization, up to 8 days, if given before angiography 1, 2, 4
• Continue fondaparinux for the duration of hospitalization, up to 8 days, if given before angiography 2, 4

Risk Stratification and Invasive Strategy Selection

Early Invasive Strategy (Angiography within 24-48 hours) is indicated for:

• Refractory angina or recurrent symptoms 1, 2, 4
• Hemodynamic instability 1, 4
• Electrical instability (life-threatening arrhythmias) 1, 4
• Elevated cardiac biomarkers 1, 4
• High GRACE or TIMI risk score 1, 2, 4

Conservative Strategy is appropriate for:

• Lower-risk patients without ongoing ischemia 1, 2, 4
• Patients with significant comorbidities where invasive risks outweigh benefits 1, 4
• In these patients, perform non-invasive stress test (preferably with imaging) or coronary CT angiography before deciding on invasive approach 3

Post-Angiography Management

If PCI is Selected:

• Continue aspirin indefinitely 2, 4
• Administer P2Y12 inhibitor loading dose if not started before diagnostic angiography 1, 2, 4

If CABG is Selected:

• Continue aspirin 2, 4
• Discontinue clopidogrel 5-7 days before elective CABG 1, 2, 4
• Stop prasugrel at least 7 days before any surgery 4, 5
• Stop ticagrelor at least 5 days before surgery 4

If Medical Therapy is Selected:

• Continue aspirin 2
• Administer clopidogrel loading dose if not given before diagnostic angiography 2

Long-Term Secondary Prevention

Cardiac Function Assessment:

• Measure left ventricular ejection fraction (LVEF) in all patients 1, 2, 4
• If LVEF ≤0.40, consider diagnostic angiography 1, 2, 4
• If LVEF >0.40, consider stress testing 2, 4

Pharmacologic Therapy:

• Initiate ACE inhibitors for patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes 1, 2, 4
• Consider ARBs for ACE inhibitor-intolerant patients 2, 4
• Continue beta-blockers indefinitely in all NSTEMI patients without contraindications 1, 4
• Initiate high-intensity statin therapy regardless of baseline LDL levels 1, 2

Anticoagulation for Special Populations:

• For patients requiring long-term oral anticoagulation, add warfarin to DAPT with target INR 2.0-3.0 2

Critical Contraindications and Pitfalls

Medications to Avoid:

• Do not administer NSAIDs (except aspirin) during hospitalization due to increased mortality, reinfarction, hypertension, heart failure, and myocardial rupture 1, 2
• Do not give immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 1, 2
• Avoid intravenous ACE inhibitors within the first 24 hours due to hypotension risk (exception: refractory hypertension) 1, 2
• Fibrinolytic therapy is contraindicated in NSTEMI patients without ST-segment elevation 1

Glycoprotein IIb/IIIa Inhibitors:

• Do not routinely administer GP IIb/IIIa antagonists in patients in whom coronary anatomy is not known 3

Bleeding Risk Management:

• Do not start prasugrel in patients likely to undergo urgent CABG 5
• When possible, discontinue prasugrel at least 7 days prior to any surgery 5
• Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, PCI, CABG, or other surgical procedures while on prasugrel 5
• If possible, manage bleeding without discontinuing antiplatelet therapy, as discontinuation (particularly in the first few weeks after ACS) increases risk of subsequent cardiovascular events 5

Additional Biomarkers:

• Do not routinely measure additional biomarkers such as h-FABP, copeptin, mid-regional pro-A-type natriuretic peptide, high-sensitivity C-reactive protein, mid-regional pro-adrenomedullin, or GDF-15 for diagnosis or routine risk assessment 3