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

Treatment of NSTEMI

All patients with NSTEMI should receive immediate aspirin 162-325 mg (non-enteric formulation), admission to a monitored unit with continuous rhythm monitoring, dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor (preferably ticagrelor), parenteral anticoagulation, and risk stratification to determine timing of invasive strategy within 2-72 hours based on clinical risk factors. 1, 2, 3

Immediate Management (First Hour)

• Aspirin: Administer 162-325 mg immediately as a non-enteric formulation, regardless of prior aspirin use 1, 2, 3
• Monitoring: Admit to a monitored unit with continuous cardiac rhythm monitoring for at least 24 hours 1, 2
• Oxygen: Only administer supplemental oxygen if arterial oxygen saturation is <90%; routine oxygen is not indicated 1, 3
• Nitroglycerin: Use sublingual or intravenous nitroglycerin for ongoing chest pain, but avoid if systolic BP <90 mmHg, severe bradycardia, tachycardia without heart failure, right ventricular infarction, or recent phosphodiesterase inhibitor use (within 24-48 hours) 4, 1, 3
• Beta-blockers: Initiate oral beta-blockers to reduce myocardial oxygen demand unless contraindications exist (heart failure signs, low-output state, hemodynamic instability) 1, 3
• Morphine: Consider morphine sulfate intravenously only for uncontrolled ischemic chest discomfort despite nitroglycerin, though use cautiously as it may delay P2Y12 inhibitor absorption 2

Antiplatelet Therapy Strategy

Aspirin Maintenance

• Continue aspirin 75-100 mg daily indefinitely after the initial loading dose 1, 2, 3
• When used with ticagrelor, aspirin must be limited to 81 mg daily, as higher doses increase bleeding without improving efficacy 3

P2Y12 Inhibitor Selection (Critical Decision Point)

Ticagrelor is the preferred P2Y12 inhibitor for all NSTEMI patients regardless of planned treatment strategy (invasive or conservative). 4, 1, 2, 3

• Ticagrelor: Loading dose 180 mg, then 90 mg twice daily—preferred over clopidogrel due to superior outcomes 4, 1, 2, 3
• Prasugrel: Only after coronary angiography and only if PCI is planned; loading dose 60 mg, then 10 mg daily 5
  • Contraindicated in patients with prior stroke or TIA 5
  • Not recommended in patients ≥75 years (except high-risk situations like diabetes or prior MI) or weight <60 kg (consider 5 mg maintenance dose) 5
• Clopidogrel: Loading dose 300-600 mg, then 75 mg daily—only if ticagrelor or prasugrel are contraindicated or unavailable 2, 6
  • Less effective in CYP2C19 poor metabolizers; consider genetic testing if available 6

Duration of P2Y12 Inhibitor

• Continue P2Y12 inhibitor for at least 12 months after NSTEMI, regardless of whether a stent was placed 4, 1, 2

Timing Considerations

• For conservative strategy: Administer ticagrelor loading dose once NSTEMI diagnosis is established 4
• For invasive strategy: Optimal timing of ticagrelor loading (upstream vs. at time of PCI) is not definitively established, but can be given at presentation 4
• Prasugrel should NOT be given upstream—only after coronary anatomy is known and PCI is planned 5

Anticoagulation Strategy

All NSTEMI patients require parenteral anticoagulation in addition to antiplatelet therapy. 4, 1, 2, 3

Anticoagulant Options (Choose One):

• Enoxaparin: 1 mg/kg subcutaneously every 12 hours (preferred over unfractionated heparin for ease of use) 2, 3

  • Reduce to 1 mg/kg once daily if CrCl <30 mL/min 3
  • Continue for duration of hospitalization, up to 8 days if given before angiography 2

• Fondaparinux: 2.5 mg subcutaneously once daily 2

  • Continue for duration of hospitalization, up to 8 days if given before angiography 2
  • Contraindicated if CrCl <20 mL/min 2

• Unfractionated heparin: Bolus 60 units/kg (maximum 4000 units), then infusion 12 units/kg/hour (maximum 1000 units/hour) adjusted to aPTT 2, 3

  • Continue for at least 48 hours or until discharge if given before angiography 2

• Bivalirudin: Alternative option, particularly if high bleeding risk 2, 3

Important Anticoagulation Pitfall:

• Do NOT switch between anticoagulants unnecessarily, as this increases bleeding risk 3
• If fondaparinux is used, add unfractionated heparin during PCI to prevent catheter thrombosis 4

Risk Stratification and Invasive Strategy Timing (Critical Algorithm)

Immediate Invasive Strategy (<2 hours):

Indicated for very high-risk patients with any of the following: 4, 3

• Refractory or recurrent angina despite medical therapy
• Hemodynamic instability or cardiogenic shock
• Life-threatening arrhythmias or cardiac arrest
• Mechanical complications (acute mitral regurgitation, ventricular septal defect, free wall rupture)
• Acute heart failure
• Recurrent dynamic ST-segment or T-wave changes

Early Invasive Strategy (<24 hours):

Indicated for high-risk patients with any of the following: 4, 1, 2, 3

• Elevated cardiac biomarkers (troponin or CK-MB)
• Dynamic ST-segment or T-wave changes (symptomatic or silent)
• High GRACE score (>140) or TIMI score (≥3)
• Diabetes mellitus
• Renal insufficiency (eGFR <60 mL/min/1.73m²)
• Left ventricular ejection fraction <40%
• Early post-infarction angina
• Recent PCI or prior CABG

Invasive Strategy (<72 hours):

Appropriate for intermediate-risk patients without recurrence of symptoms but with at least one intermediate-risk criterion 4

Selective Invasive Strategy (Consider Non-Invasive Testing First):

For low-risk patients with: 4

• No recurrence of chest pain
• No signs of heart failure
• No abnormalities in initial or subsequent ECG
• No elevation in cardiac troponin levels

Perform non-invasive stress test (preferably with imaging) before deciding on invasive approach 4

Glycoprotein IIb/IIIa Inhibitors

Routine upstream use of GP IIb/IIIa inhibitors is NOT recommended. 4

• The EARLY ACS trial showed that early routine eptifibatide administration did not reduce ischemic events compared to delayed provisional use, but significantly increased major bleeding (2.6% vs 1.8%, P=0.02) 4
• Consider provisional use at time of PCI only for specific high-risk situations (large thrombus burden, no-reflow phenomenon) 4

Post-Angiography Management

If PCI is Performed:

• Continue aspirin indefinitely 1, 2
• Continue P2Y12 inhibitor for at least 12 months 1, 2
• If P2Y12 inhibitor not given before angiography, administer loading dose immediately 1, 2
• Use radial access when possible to reduce bleeding complications 4

If CABG is Selected:

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

If Medical Management is Selected:

• Continue aspirin and P2Y12 inhibitor 2
• Continue anticoagulation as outlined above 2

Long-Term Secondary Prevention

Mandatory Interventions:

• Aspirin: 81 mg daily indefinitely 1, 2, 3
• P2Y12 inhibitor: Continue for at least 12 months 1, 2
• High-intensity statin therapy: Initiate regardless of baseline LDL levels (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) 2, 3
• Beta-blockers: Continue indefinitely, especially if heart failure or LV dysfunction present 1, 3
• ACE inhibitors: Initiate for patients with heart failure, LV dysfunction (LVEF <40%), hypertension, or diabetes 1, 2, 3
• ARBs: Use for ACE inhibitor-intolerant patients 1, 2

Additional Assessments:

• Measure LVEF in all patients 2, 3

  • If LVEF ≤40%, consider diagnostic angiography if not already performed 2
  • If LVEF >40%, consider stress testing 2

• Lifestyle modifications: Smoking cessation, cardiac rehabilitation enrollment, regular physical activity, healthy diet 3

Critical Pitfalls to Avoid

• Never use NSAIDs (except aspirin) during hospitalization—they increase mortality, reinfarction, hypertension, heart failure, and myocardial rupture risk 1, 2
• Never use immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 1, 2
• Never use intravenous ACE inhibitors within the first 24 hours due to hypotension risk 2
• Avoid omeprazole or esomeprazole with clopidogrel, as they significantly reduce its antiplatelet activity; use alternative PPIs if needed 6
• Do not delay invasive strategy in high-risk patients—the 24-hour window for early invasive strategy should be strictly adhered to 4, 3
• Do not give prasugrel before knowing coronary anatomy—wait until after angiography and only if PCI is planned 5
• Do not discontinue P2Y12 inhibitor prematurely—particularly in the first few weeks after ACS, as this dramatically increases risk of subsequent cardiovascular events 5