What is the medical management of Non-ST-Elevation Myocardial Infarction (NSTEMI)?

Medical Management of NSTEMI

Immediately administer aspirin 162-325 mg (non-enteric, chewed or oral), admit to a monitored unit, initiate dual antiplatelet therapy with ticagrelor (180 mg loading, then 90 mg twice daily), add parenteral anticoagulation (unfractionated heparin or enoxaparin), start oral beta-blockers unless contraindicated, and perform risk stratification to determine timing of angiography within 24-48 hours for high-risk patients. 1, 2, 3

Immediate Initial Management (First Hours)

Antiplatelet Therapy

• Aspirin 162-325 mg immediately as a non-enteric formulation, either chewed or taken orally, regardless of prior aspirin use 1, 2, 3
• Continue aspirin 75-162 mg daily indefinitely after the loading dose 4, 1, 2
• Add ticagrelor as the preferred P2Y12 inhibitor: loading dose 180 mg, then 90 mg twice daily, regardless of invasive or conservative strategy 1, 2, 3
• Alternative P2Y12 inhibitors include prasugrel or clopidogrel (300-600 mg loading dose, then 75 mg daily), though ticagrelor is preferred 3, 5
• Continue P2Y12 inhibitor for at least 12 months unless high bleeding risk 1, 2, 3

Anticoagulation

• Administer parenteral anticoagulation to all NSTEMI patients in addition to antiplatelet therapy 1, 2, 3
• Unfractionated heparin (UFH): continue for at least 48 hours or until discharge if given before angiography 1, 2, 3
• Enoxaparin: continue for duration of hospitalization, up to 8 days, if given before angiography 2, 3
• Fondaparinux: continue for duration of hospitalization, up to 8 days, if given before angiography 3

Supportive Care and Monitoring

• Admit to a monitored unit with continuous cardiac rhythm monitoring for at least 24 hours to detect arrhythmias 1, 2
• Supplemental oxygen only if arterial oxygen saturation <90%; routine oxygen is not indicated 1, 2
• Nitroglycerin (sublingual or IV) 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 phosphodiesterase inhibitor use within 24 hours (sildenafil) or 48 hours (tadalafil) 1, 2
• Morphine sulfate IV may be considered for uncontrolled ischemic chest pain despite nitroglycerin 3

Beta-Blocker Therapy

• Initiate oral beta-blockers (preferred over IV) to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility 4, 1, 2
• Continue beta-blockers indefinitely in all NSTEMI patients without contraindications 4, 2
• For patients with moderate or severe LV failure, use gradual titration scheme 4
• Avoid IV beta-blockers in patients with signs of heart failure, low-output state, or cardiogenic shock risk factors 2

Risk Stratification and Invasive Strategy Timing

Early Invasive Strategy (Angiography Within 24-48 Hours)

Indicated for high-risk patients with: 1, 2, 3

• Refractory angina despite medical therapy
• Hemodynamic instability
• Electrical instability (ventricular arrhythmias)
• Elevated cardiac biomarkers (troponin)
• High GRACE or TIMI risk score

Conservative Strategy

• Appropriate for lower-risk patients without ongoing ischemia or patients with significant comorbidities where invasive risks outweigh benefits 2, 3
• These patients still require medical management with dual antiplatelet therapy and anticoagulation 3

Post-Angiography Management

After PCI

• Continue aspirin indefinitely 2, 3
• Administer P2Y12 inhibitor loading dose if not given before angiography 2, 3
• For drug-eluting stents: aspirin 162-325 mg daily for at least 3-6 months (depending on stent type), then 75-162 mg daily indefinitely 4
• Clopidogrel 75 mg daily for at least 12 months after DES placement 4

After CABG

• Continue aspirin 2, 3
• Discontinue clopidogrel 5-7 days before elective CABG 2, 3

Medical Management Without Revascularization

• Continue aspirin and P2Y12 inhibitor 3
• Clopidogrel should be given for minimum of 1 month, ideally up to 1 year (minimum 2 weeks if increased bleeding risk) 4

Long-Term Secondary Prevention

ACE Inhibitors/ARBs

• Initiate ACE inhibitors for patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes mellitus 4, 1, 2, 3
• Continue ACE inhibitors indefinitely 4
• ARBs should be prescribed for patients intolerant of ACE inhibitors who have clinical or radiological signs of heart failure and LVEF <0.40 4, 1, 3
• ACE inhibitors are reasonable for all NSTEMI patients even without LV dysfunction, hypertension, or diabetes 4
• Avoid IV ACE inhibitors within first 24 hours due to hypotension risk (exception: refractory hypertension) 2

Aldosterone Receptor Blockade

• Prescribe long-term aldosterone receptor blockade (e.g., eplerenone) for patients without significant renal dysfunction (creatinine clearance >30 mL/min) or hyperkalemia (potassium ≤5 mEq/L) who are already receiving therapeutic doses of ACE inhibitor, have LVEF ≤0.40, and have either symptomatic heart failure or diabetes mellitus 4

Statin Therapy

• Initiate high-intensity statin therapy regardless of baseline LDL levels 2, 3

Left Ventricular Function Assessment

• Measure LVEF in all patients 2, 3
• If LVEF ≤0.40, consider diagnostic angiography 1, 2, 3
• If LVEF >0.40, consider stress testing 3

Anticoagulation for Other Indications

• For patients requiring long-term oral anticoagulation (e.g., atrial fibrillation): triple antithrombotic therapy (anticoagulant preferably DOAC + aspirin + clopidogrel) for up to 1 month (typically 1 week or until hospital discharge), followed by DOAC + clopidogrel for up to 1 year, then DOAC monotherapy thereafter 6
• Target INR 2.0-3.0 if warfarin is used 4, 3

Critical Contraindications and Pitfalls

Medications to Avoid

• NSAIDs (except aspirin) are contraindicated during hospitalization due to increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture 4, 1, 2, 3
• Immediate-release dihydropyridine calcium channel blockers should not be given without adequate beta-blockade 1, 2, 3
• Fibrinolytic therapy is contraindicated in NSTEMI patients without ST-segment elevation 2

Drug-Drug Interactions

• Avoid omeprazole or esomeprazole with clopidogrel due to CYP2C19 inhibition reducing clopidogrel's antiplatelet effect 5
• Consider alternative P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers 5
• Opioids decrease clopidogrel exposure; consider parenteral antiplatelet agent if opioids are needed 5
• Use gastro-protective agents (proton-pump inhibitors other than omeprazole/esomeprazole) for patients with gastrointestinal bleeding risk 4

Premature Discontinuation

• Premature discontinuation of antiplatelet therapy increases risk of cardiovascular events 5
• Discontinue P2Y12 inhibitor 5 days prior to elective surgery with major bleeding risk 5

Special Populations

• For aspirin-allergic patients: use clopidogrel alone indefinitely or attempt aspirin desensitization 4
• For clopidogrel-allergic patients: use ticlopidine 250 mg twice daily 4
• Lower initial aspirin dose (75-162 mg daily) after PCI is reasonable if concerned about bleeding risk 4

Follow-Up and Discharge Planning

• Detailed discharge instructions should include education on medications, diet, exercise, and smoking cessation counseling 4
• Low-risk medically treated and revascularized patients should return in 2-6 weeks 4
• Higher-risk patients should return within 14 days 4
• Patients with recurrent signs/symptoms of UA or severe chronic stable angina despite medical management should undergo timely coronary angiography 4