What is the management approach for a patient presenting with Non-ST-Elevation Myocardial Infarction (NSTEMI)?

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

Immediate Initial Management

Administer aspirin 162-325 mg immediately as a non-enteric formulation (chewed or oral) upon presentation, regardless of prior aspirin use. 1

• Admit patients to a monitored unit with continuous cardiac rhythm monitoring for at least 24 hours to detect life-threatening arrhythmias 1, 2
• Provide supplemental oxygen only if arterial oxygen saturation is <90%; routine oxygen administration is not indicated 3, 1
• Administer sublingual or intravenous nitroglycerin for ongoing ischemic chest pain, but avoid if systolic blood pressure <90 mmHg or ≥30 mmHg below baseline, severe bradycardia (<50 bpm) or tachycardia (>100 bpm without heart failure), right ventricular infarction, or phosphodiesterase inhibitor use within 24 hours (sildenafil) or 48 hours (tadalafil) 1
• Initiate oral beta-blocker therapy (preferred over intravenous) to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility, unless contraindications exist such as signs of heart failure, low-output state, or cardiogenic shock risk factors 1, 4
• Consider morphine sulfate intravenously for uncontrolled ischemic chest discomfort despite nitroglycerin 4

Antiplatelet Therapy Strategy

Dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor is mandatory for all NSTEMI patients. 3, 1

• Continue aspirin 75-162 mg daily indefinitely after the initial loading dose 3, 1
• Add a P2Y12 receptor inhibitor to aspirin for 12 months unless contraindicated or high bleeding risk exists 3, 1, 2

Ticagrelor is the preferred P2Y12 inhibitor for all NSTEMI patients regardless of invasive or conservative strategy: 1, 2

• Loading dose: 180 mg orally
• Maintenance: 90 mg twice daily
• Superior outcomes compared to clopidogrel with no difference in stroke rates 2

Prasugrel is an alternative for patients naive to P2Y12 inhibitors undergoing PCI: 2, 5

• Loading dose: 60 mg orally
• Maintenance: 10 mg daily (5 mg daily if weight <60 kg) 5
• Contraindicated in patients with prior stroke or TIA (6.5% stroke rate vs 1.2% with clopidogrel) 5
• Generally not recommended in patients ≥75 years due to increased fatal and intracranial bleeding risk, except in high-risk situations (diabetes or prior MI) 5
• Discontinue at least 7 days before elective CABG 5

Clopidogrel is reserved only when ticagrelor or prasugrel are unavailable, not tolerated, or contraindicated: 2

• Loading dose: 300-600 mg orally
• Maintenance: 75 mg daily
• Discontinue 5-7 days before elective CABG 3, 4

Anticoagulant Therapy

All NSTEMI patients require parenteral anticoagulation in addition to antiplatelet therapy. 3, 2, 4

Agent selection based on clinical scenario:

• Unfractionated heparin (UFH): Continue for at least 48 hours or until discharge if given before diagnostic angiography 3, 2, 4

• Enoxaparin: Continue for duration of hospitalization, up to 8 days, if given before diagnostic angiography 3, 2, 4

• Fondaparinux: Continue for duration of hospitalization, up to 8 days, if given before diagnostic angiography 3, 2, 4

  • Critical pitfall: Must be supplemented with UFH during PCI due to risk of catheter thrombosis 4

• Bivalirudin: Either discontinue or continue at 0.25 mg/kg/hour for up to 72 hours at physician's discretion if given before diagnostic angiography 3, 4

Do not switch between anticoagulants as this increases bleeding risk. 4

Risk Stratification and Invasive Strategy Timing

An immediate invasive strategy (<2 hours) is indicated for very high-risk patients with: 4

• Refractory or recurrent angina despite medical therapy 3, 4
• Hemodynamic instability or cardiogenic shock 3, 1, 4
• Life-threatening ventricular arrhythmias or cardiac arrest 4
• Mechanical complications of MI 4

An early invasive strategy (angiography within 24-48 hours) is indicated for high-risk patients with: 3, 1, 2, 4

• Elevated cardiac biomarkers (troponin) 3, 1, 4
• Dynamic ST-segment or T-wave changes 4
• High GRACE or TIMI risk score 3, 1, 4
• Electrical instability 1, 4

The TIMACS trial demonstrated that early invasive strategy within 12-24 hours (median 14 hours) is preferred in high-risk patients, while the ABOARD trial showed that immediate invasive strategy (median 1.1 hour) provides no incremental benefit over early strategy. 3

A conservative strategy is appropriate for lower-risk patients without ongoing ischemia or patients with significant comorbidities where invasive risks outweigh benefits. 1, 2, 4

Post-Angiography Management

If PCI is performed:

• Continue aspirin indefinitely 3, 1, 4
• Administer P2Y12 inhibitor loading dose if not given before diagnostic angiography 3, 1, 4
• Discontinue anticoagulant therapy after PCI for uncomplicated cases 3
• Discontinue intravenous GP IIb/IIIa inhibitor if started previously 3

If CABG is selected:

• Continue aspirin 3, 4
• Discontinue clopidogrel 5-7 days before elective CABG 3, 4
• Discontinue prasugrel at least 7 days before surgery 2, 5
• Discontinue ticagrelor at least 5 days before surgery 2

If medical therapy is selected:

• Continue aspirin 3, 4
• Administer P2Y12 inhibitor loading dose if not given before diagnostic angiography 3, 4
• Discontinue intravenous GP IIb/IIIa inhibitor if started previously 3
• Continue anticoagulation as outlined above based on agent used 3, 4

Long-Term Secondary Prevention

Measure left ventricular ejection fraction (LVEF) in all patients: 1, 2, 4

• If LVEF ≤0.40, consider diagnostic angiography 1, 4
• If LVEF >0.40, consider stress testing 2, 4

ACE inhibitors are mandatory for patients with: 3, 1, 4

• Heart failure
• Left ventricular dysfunction (LVEF <0.40)
• Hypertension
• Diabetes
• Avoid intravenous ACE inhibitors within first 24 hours due to hypotension risk (exception: refractory hypertension) 1

Angiotensin receptor blockers (ARBs) provide an alternative for patients intolerant to ACE inhibitors. 3, 2, 4

Beta-blockers should be continued indefinitely in all NSTEMI patients without contraindications, particularly those with LVEF ≤40%. 3, 1, 4

Mineralocorticoid receptor antagonists (preferably eplerenone) are recommended in patients with LVEF ≤35% and either heart failure or diabetes, but no significant renal dysfunction or hyperkalemia. 3

High-intensity statin therapy should be initiated regardless of baseline LDL levels. 1, 4

For patients requiring long-term oral anticoagulation (e.g., atrial fibrillation):

• Use triple antithrombotic therapy (oral anticoagulant + aspirin + clopidogrel) for the shortest duration possible, typically 1 week to 1 month 4, 6
• Transition to dual therapy (oral anticoagulant + clopidogrel) for up to 1 year 6
• Then oral anticoagulant monotherapy thereafter 6
• Prefer direct oral anticoagulants (DOACs) over warfarin 4, 6
• Critical consideration: Bleeding risk increases from 4-6% with dual therapy to 10-14% with triple therapy 4

Critical Contraindications and Pitfalls

NSAIDs (except aspirin) are contraindicated during hospitalization due to increased mortality, reinfarction, hypertension, heart failure, and myocardial rupture. 1, 4

Immediate-release dihydropyridine calcium channel blockers should not be given without adequate beta-blockade. 1, 4

Fibrinolytic therapy is contraindicated in NSTEMI patients without ST-segment elevation. 1

GP IIb/IIIa inhibitors should not be used routinely upstream due to increased bleeding risk without reduction in ischemic events. The EARLY ACS trial demonstrated no benefit of early routine eptifibatide administration compared to delayed provisional use. 3, 4

Morphine coadministration with prasugrel decreases Cmax of prasugrel's active metabolite by 31%, potentially delaying platelet inhibition by up to 2 hours in some patients. 5

Do not administer prasugrel loading dose until coronary anatomy is established in UA/NSTEMI patients, as urgent CABG after prasugrel carries substantial bleeding risk. 5