What is the management approach for Acute Coronary Syndrome (ACS) Non-ST-Elevation Myocardial Infarction (NSTEMI)?

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

All patients with NSTEMI should receive immediate aspirin 162-325 mg (chewed or non-enteric formulation), admission to a monitored unit, dual antiplatelet therapy, parenteral anticoagulation, and risk stratification to determine timing of invasive strategy within 24-72 hours based on clinical risk factors. 1, 2

Immediate Management (First Hour)

Initial Medications

• Aspirin: Administer 162-325 mg immediately as non-enteric formulation (chewed or oral), regardless of prior aspirin use 3, 2
• Oxygen: Only if arterial oxygen saturation <90%; routine oxygen is not indicated 1, 2
• Nitroglycerin: Sublingual or IV for ongoing 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
  • Phosphodiesterase inhibitor use within 24 hours (sildenafil) or 48 hours (tadalafil) 2
• Beta-blockers: Initiate oral beta-blocker therapy (preferred over IV) to reduce myocardial oxygen demand unless contraindications exist (heart failure signs, low-output state, cardiogenic shock risk) 1, 2

Monitoring

• Admit to monitored unit with continuous cardiac rhythm monitoring for at least 24 hours 1, 2
• Place defibrillator patches if ongoing ischemia until urgent revascularization performed 3

Laboratory Assessment

• Cardiac troponin (preferably high-sensitivity) with results available within 60 minutes; repeat at 1-3 hours 3
• Serum creatinine, hemoglobin, hematocrit, platelet count, blood glucose 3
• Lipid profile in early phase of admission 3

Antiplatelet Therapy

Aspirin Maintenance

• Continue aspirin indefinitely at 81 mg daily (this is the preferred maintenance dose) 3, 1
• When used with ticagrelor, aspirin must be 81 mg daily (higher doses increase bleeding without improving efficacy) 3

P2Y12 Inhibitor Selection

For patients managed with early invasive strategy (PCI planned):

The choice depends on timing and patient characteristics:

• Ticagrelor (preferred agent regardless of strategy): Loading dose 180 mg, then 90 mg twice daily 3, 1, 2

  • Can be given before or after angiography
  • Preferred over clopidogrel based on mortality benefit 3

• Prasugrel: 60 mg loading dose, then 10 mg daily 3, 4

  • Only after coronary anatomy is known (do not give until after angiography in NSTEMI) 4
  • Contraindicated in patients with prior stroke/TIA 4
  • Generally not recommended in patients ≥75 years old (except high-risk situations with diabetes or prior MI) 4
  • Reduce dose to 5 mg daily if body weight <60 kg 4
  • Showed superiority over ticagrelor in ISAR-REACT-5 trial (6.9% vs 9.3% events, P=0.006) 5

• Clopidogrel: 300-600 mg loading dose, then 75 mg daily 3

  • Acceptable alternative if ticagrelor or prasugrel contraindicated or not tolerated 3
  • Less potent than newer agents (30-40% high on-treatment platelet reactivity vs 3% with prasugrel/ticagrelor) 5

Duration: Continue P2Y12 inhibitor for at least 12 months in all patients without contraindications 3, 1, 2

Anticoagulation Therapy

All patients require parenteral anticoagulation in addition to antiplatelet therapy. 3, 1, 2 Choose one of the following:

• Enoxaparin: 1 mg/kg SC every 12 hours (reduce to 1 mg/kg SC once daily if CrCl <30 mL/min), continued for duration of hospitalization or until PCI performed; initial IV loading dose of 30 mg used in selected patients 3

• Fondaparinux: 2.5 mg SC daily, continued for duration of hospitalization or until PCI performed 3

  • Critical: If PCI performed while on fondaparinux, must add additional anticoagulant with anti-IIa activity (UFH or bivalirudin) due to catheter thrombosis risk 3

• Bivalirudin: 0.10 mg/kg loading dose followed by 0.25 mg/kg/hour (only in patients managed with early invasive strategy), continued until diagnostic angiography or PCI, with provisional GP IIb/IIIa inhibitor use 3

• Unfractionated heparin (UFH): Initial loading dose 60 IU/kg (maximum 4000 IU) with initial infusion 12 IU/kg/hour (maximum 1000 IU/h), adjusted per aPTT to maintain therapeutic anticoagulation, continued for 48 hours or until PCI performed 3, 2

Risk Stratification and Invasive Strategy Timing

Urgent/Immediate Invasive Strategy (within 2 hours)

Indicated for patients with: 3, 1, 2

• Refractory angina despite medical therapy
• Hemodynamic instability
• Electrical instability (life-threatening ventricular arrhythmias)
• Cardiogenic shock

Early Invasive Strategy (within 24 hours)

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

• Elevated cardiac biomarkers (troponin)
• High GRACE or TIMI risk score
• Dynamic ST-segment or T-wave changes
• Diabetes mellitus
• Renal insufficiency (eGFR <60 mL/min/1.73m²)
• Reduced left ventricular function (LVEF <40%)
• Early post-infarction angina
• Recent PCI or prior CABG

Delayed Invasive Strategy (within 24-72 hours)

Reasonable for patients not at high/intermediate risk 3

Ischemia-Guided (Conservative) Strategy

May be considered for: 3

• Low-risk patients without ongoing ischemia
• Patients with extensive comorbidities where revascularization risks outweigh benefits (hepatic, renal, pulmonary failure; cancer) 3
• Troponin-negative patients with low likelihood of ACS 3

Critical Contraindications

Class III: Harm

• Fibrinolytic therapy is absolutely contraindicated in NSTEMI patients (without ST-elevation, true posterior MI, or new LBBB) 3, 2
• NSAIDs (except aspirin) should not be administered during hospitalization due to increased mortality, reinfarction, hypertension, heart failure, and myocardial rupture 1, 2
• Immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 1, 2
• IV ACE inhibitors within first 24 hours due to hypotension risk (exception: refractory hypertension) 2

Post-PCI Management

If PCI with Stent Placement

• Continue aspirin indefinitely 3, 2
• Continue P2Y12 inhibitor (clopidogrel 75 mg daily, prasugrel 10 mg daily, or ticagrelor 90 mg twice daily) for at least 12 months 3, 2
• Administer P2Y12 inhibitor loading dose if not given before angiography 2

If CABG Required

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

Long-Term Secondary Prevention

Mandatory Therapies

• Aspirin 81 mg daily indefinitely 3, 1, 2
• High-intensity statin therapy regardless of baseline LDL levels; target LDL-C <55 mg/dL (<1.4 mmol/L) with ≥50% reduction from baseline 2
• Beta-blockers continued indefinitely in all NSTEMI patients without contraindications 2
• ACE inhibitors for patients with heart failure, LV dysfunction (LVEF <40%), hypertension, or diabetes 3, 1, 2
• ARBs if ACE inhibitor not tolerated 1, 2

Additional Measures

• Measure LVEF in all patients; if LVEF ≤40%, consider diagnostic angiography 1, 2
• Proton pump inhibitor for patients at high risk of GI bleeding on dual antiplatelet therapy 2
• Cardiac rehabilitation enrollment 2
• Lifestyle modifications: smoking cessation, regular physical activity (≥30 minutes, ≥3 times weekly), healthy diet 2

Common Pitfalls to Avoid

1. Never discharge NSTEMI patients on aspirin monotherapy—dual antiplatelet therapy for 12 months is mandatory 2
2. Do not use aspirin >81 mg daily when combining with ticagrelor—increases bleeding without efficacy benefit 3, 2
3. Do not give prasugrel before knowing coronary anatomy in NSTEMI—wait until after angiography 4
4. Do not forget to add anti-IIa anticoagulant if performing PCI on fondaparinux—catheter thrombosis risk 3
5. Avoid upstream GP IIb/IIIa inhibitors—deferred use reduces bleeding without compromising efficacy 3
6. Do not assume beta-blockers are contraindicated in all heart failure—they are beneficial unless signs of acute decompensation, low-output state, or cardiogenic shock 2