What is the appropriate management and treatment for a patient diagnosed with Non-ST-Elevation Myocardial Infarction (NSTEMI)?

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

Administer aspirin 162-325 mg immediately (non-enteric, chewed or oral), initiate parenteral anticoagulation, perform risk stratification within 10 minutes, and proceed with early invasive strategy (angiography within 24-48 hours) for high-risk patients or conservative management for lower-risk patients, followed by dual antiplatelet therapy for 12 months and aggressive secondary prevention. 1, 2

Immediate Initial Management (Within 10 Minutes)

The first priority is rapid triage and working diagnosis based on chest pain quality, CAD likelihood assessment, and ECG findings to distinguish NSTEMI from STEMI or low-probability ACS. 3

• Aspirin 162-325 mg must be administered immediately as non-enteric formulation, either chewed or taken orally, regardless of prior aspirin use. 1, 2
• Admit to a monitored unit with continuous cardiac rhythm monitoring for at least 24 hours to detect life-threatening arrhythmias. 1, 2
• Supplemental oxygen should only be provided if arterial oxygen saturation is <90%; routine oxygen administration is not indicated. 1, 2
• Draw blood immediately for troponin T or I, CK-MB, creatinine, hemoglobin, and leukocyte count with results available within 60 minutes. 3

Anti-Ischemic Therapy

• 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, 2
• Consider morphine sulfate intravenously for uncontrolled ischemic chest discomfort despite nitroglycerin. 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, 2

Antiplatelet Therapy Strategy

After the initial aspirin loading dose, continue aspirin 75-162 mg daily indefinitely. 1, 2

• Add a P2Y12 receptor inhibitor to aspirin for dual antiplatelet therapy for 12 months unless contraindicated or high bleeding risk. 1, 2
• Ticagrelor is the preferred P2Y12 inhibitor for all NSTEMI patients (loading dose 180 mg, then 90 mg twice daily), demonstrating superior outcomes regardless of invasive or conservative strategy. 1, 2
• If ticagrelor is unavailable or contraindicated, administer clopidogrel loading dose of 300-600 mg if early conservative strategy is selected or if PCI is planned and not started before diagnostic angiography. 1, 2, 4

Critical Pharmacogenomic Consideration

• Clopidogrel effectiveness is significantly reduced in CYP2C19 poor metabolizers (approximately 2% of White, 4% of Black, and 14% of Chinese patients), who form less active metabolite and have diminished platelet inhibition. 4
• Consider genetic testing for CYP2C19 status and use an alternative P2Y12 inhibitor (ticagrelor or prasugrel) in identified poor metabolizers. 4
• Avoid concomitant use of clopidogrel with omeprazole or esomeprazole as they significantly reduce antiplatelet activity through CYP2C19 inhibition. 4

Anticoagulant Therapy

All NSTEMI patients require parenteral anticoagulation in addition to antiplatelet therapy. 1, 2, 5

• Unfractionated heparin (UFH) should be continued for at least 48 hours or until discharge if given before diagnostic angiography. 1, 2
• Enoxaparin should be continued for the duration of hospitalization, up to 8 days, if given before diagnostic angiography. 1, 2
• Fondaparinux should be continued for the duration of hospitalization, up to 8 days, if given before diagnostic angiography, but must be supplemented with UFH during PCI to prevent catheter thrombosis. 1
• Do not switch between anticoagulants as this increases bleeding risk. 1

Risk Stratification and Management Strategy Selection

An early invasive strategy (angiography within 24-48 hours) is indicated for high-risk patients with: 1, 2, 6

• Refractory or recurrent angina despite medical therapy
• Hemodynamic instability or cardiogenic shock
• Electrical instability (life-threatening arrhythmias)
• Elevated cardiac biomarkers (troponin)
• High GRACE or TIMI risk score
• Dynamic ST-segment or T-wave changes

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

• Very high-risk patients (refractory angina, hemodynamic instability, life-threatening arrhythmias) require immediate invasive strategy within 2 hours. 1

Post-Angiography Management

If PCI is Performed:

• Continue aspirin indefinitely and administer P2Y12 inhibitor loading dose if not given before angiography. 1, 2
• Continue dual antiplatelet therapy for at least 12 months regardless of stent placement. 1

If CABG is Selected:

• Continue aspirin indefinitely but discontinue clopidogrel 5-7 days before elective CABG to reduce bleeding risk. 1, 2
• Discontinue ticagrelor 5 days before elective CABG and prasugrel at least 7 days before CABG. 1

If Medical Therapy is Selected:

• Continue aspirin indefinitely and administer clopidogrel loading dose if not given before angiography. 1, 2

Long-Term Secondary Prevention

• Measure left ventricular ejection fraction (LVEF) in all patients. 1, 2
• If LVEF ≤0.40, consider diagnostic angiography if not already performed. 1, 2
• If LVEF >0.40, consider stress testing. 1
• Initiate ACE inhibitors for patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes. 1, 2
• Consider ARBs for ACE inhibitor-intolerant patients. 1, 2
• Initiate high-intensity statin therapy regardless of baseline LDL levels. 1, 2
• Continue beta-blockers indefinitely in all NSTEMI patients without contraindications. 2

For Patients Requiring Long-Term Oral Anticoagulation:

• Use triple antithrombotic therapy (anticoagulant + aspirin + P2Y12 inhibitor) for the shortest duration possible, typically 1 week to 1 month. 1
• After initial period, transition to dual therapy (anticoagulant + P2Y12 inhibitor) for up to 1 year. 1, 5
• After 1 year, continue anticoagulant monotherapy. 5
• Preferably use DOAC over warfarin; if warfarin is used, target INR 2.0-3.0. 1

Critical Contraindications and Pitfalls to Avoid

• NSAIDs (except aspirin) are absolutely contraindicated during hospitalization due to increased risks of 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 (exception: refractory hypertension). 1, 2
• Do not administer intravenous beta-blockers to patients with signs of heart failure, low-output state, or cardiogenic shock risk factors. 2
• Fibrinolytic therapy is contraindicated in NSTEMI patients without ST-segment elevation. 2
• Avoid routine upstream use of GP IIb/IIIa inhibitors due to increased bleeding risk without reduction in ischemic events. 1
• Patients who have received nitrates must not take PDE5 inhibitors (sildenafil within 24 hours, tadalafil within 48 hours) due to potentially dangerous hypotensive effects. 7