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

Initial Management of NSTEMI

Immediately administer aspirin 162-325 mg orally upon presentation, initiate anticoagulation with unfractionated heparin or enoxaparin, add a P2Y12 inhibitor (clopidogrel 300-600 mg loading dose or ticagrelor 180 mg), and perform risk stratification to determine timing of invasive strategy within 24 hours. 1, 2, 3

Immediate Stabilization and Monitoring

• Admit to a monitored unit with continuous cardiac rhythm monitoring for at least 24 hours to detect arrhythmias and electrical instability 1, 3
• Administer supplemental oxygen only if arterial oxygen saturation is <90% (avoid routine oxygen in normoxic patients) 1, 3
• Consider sublingual or intravenous nitroglycerin for ongoing ischemic chest pain, unless contraindicated by systolic blood pressure <90 mmHg, severe bradycardia or tachycardia, right ventricular infarction, or recent phosphodiesterase inhibitor use (within 24-48 hours) 1, 3
• Initiate beta-blocker therapy to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility 1, 3
• Consider morphine sulfate intravenously for uncontrolled ischemic chest discomfort despite nitroglycerin, though use cautiously as it may delay P2Y12 inhibitor absorption 1

Antiplatelet Therapy

Aspirin is the cornerstone and must be given immediately:

• Loading dose: 162-325 mg orally (non-enteric coated for faster absorption) 1, 2, 3
• Maintenance: 75-100 mg daily indefinitely 1, 2

Add a P2Y12 inhibitor before diagnostic angiography (upstream administration):

• Ticagrelor is preferred (180 mg loading dose, then 90 mg twice daily) for superior efficacy regardless of management strategy 1, 2, 3
• Clopidogrel (300-600 mg loading dose, then 75 mg daily) is an alternative, though less potent; 600 mg loads faster but lacks rigorous safety data compared to 300 mg 4, 5
• Prasugrel (60 mg loading dose, then 10 mg daily) should NOT be given upstream in NSTEMI—wait until coronary anatomy is defined at angiography due to increased bleeding risk if urgent CABG is needed 6

Critical caveat: Clopidogrel effectiveness depends on CYP2C19 metabolism; poor metabolizers (homozygous for loss-of-function alleles) have reduced antiplatelet effect and should receive ticagrelor or prasugrel instead 5

Anticoagulation Therapy

Initiate parenteral anticoagulation immediately in all patients:

For early invasive strategy (planned angiography within 24 hours):

• Unfractionated heparin (UFH) with weight-based dosing, continued until PCI or for 48 hours if medical management 4, 1
• Enoxaparin 1 mg/kg subcutaneously every 12 hours, preferred over UFH for ease of use 4, 1
• Bivalirudin may be used, especially if GP IIb/IIIa inhibitor is omitted and clopidogrel 300 mg was given ≥6 hours before catheterization 4

For conservative strategy:

• Fondaparinux 2.5 mg subcutaneously daily is preferred due to lower bleeding risk, continued for duration of hospitalization up to 8 days 4
• Enoxaparin is also acceptable 4

Important: If fondaparinux is used and patient proceeds to PCI, give additional bolus of UFH to prevent catheter thrombosis 4

Risk Stratification and Management Strategy Selection

Perform immediate risk stratification using GRACE or TIMI score:

Early invasive strategy (angiography within 12-24 hours) is MANDATORY for:

• Refractory angina despite medical therapy 4, 1, 2
• Hemodynamic instability (hypotension, shock) 4, 1, 2
• Electrical instability (ventricular arrhythmias, cardiac arrest) 4, 1, 2
• Elevated cardiac troponin with high-risk features 4, 1, 2
• GRACE score >140 or high TIMI risk score 4, 1, 2
• Recurrent ischemia, heart failure, or serious arrhythmias during hospitalization 4

Conservative strategy (selective invasive) may be considered for:

• Low-to-intermediate risk patients (GRACE <140) who are initially stabilized 4, 1
• Patients with extensive comorbidities where revascularization risks outweigh benefits (liver failure, advanced cancer, severe pulmonary disease) 4

The 2012 ACC/AHA update clarifies timing: High-risk patients benefit from angiography within 24 hours, but there is no evidence that intervention within the first few hours provides additional benefit over a measured approach within 24 hours 4

GP IIb/IIIa Inhibitor Considerations

For invasive strategy:

• Eptifibatide or tirofiban may be added upstream (before angiography) in very high-risk patients, particularly if delay to catheterization is anticipated 4
• Abciximab should NOT be given upstream—only use if PCI is imminent with no delay to angiography 4
• GP IIb/IIIa inhibitors may be omitted if bivalirudin is used and clopidogrel 300 mg was given ≥6 hours prior 4

For conservative strategy:

• Adding eptifibatide or tirofiban is Class IIb (may be reasonable) but increases bleeding risk 4

Additional Pharmacotherapy

Beta-blockers:

• Initiate oral beta-blockers within 24 hours unless contraindicated (active heart failure, bradycardia, hypotension, heart block) 2, 3
• Continue indefinitely for secondary prevention 2

ACE inhibitors:

• Start within 24 hours for patients with heart failure, left ventricular dysfunction (LVEF <40%), hypertension, or diabetes 1, 2, 3
• Use ARBs for ACE inhibitor-intolerant patients 1, 3
• Avoid intravenous ACE inhibitors in the first 24 hours due to hypotension risk 1

Statins:

• Initiate high-intensity statin therapy (atorvastatin 80 mg or rosuvastatin 40 mg) regardless of baseline LDL cholesterol 1, 2

Critical Pitfalls to Avoid

• Never give prasugrel upstream in NSTEMI—wait for coronary anatomy definition to avoid catastrophic bleeding if urgent CABG is needed 6
• Avoid NSAIDs (except aspirin) during hospitalization—they increase mortality, reinfarction, hypertension, heart failure, and myocardial rupture risk 1, 3
• Do not use immediate-release dihydropyridine calcium channel blockers (nifedipine) without adequate beta-blockade 1, 3
• Avoid omeprazole and esomeprazole with clopidogrel—they significantly reduce its antiplatelet effect; use other PPIs if gastroprotection is needed 4, 5
• Do not delay angiography in high-risk patients for "medical stabilization"—early invasive approach (within 24 hours) reduces ischemic events 4, 1, 2

Timing Considerations

The evidence strongly supports that "early" means within 24 hours, not within 2-3 hours of presentation. The 2012 focused update found that very urgent catheterization (within hours) provides no additional benefit over a measured approach within 24 hours, and may increase bleeding risk in patients requiring urgent CABG 4. The exception is immediate catheterization for unstable patients with refractory ischemia, hemodynamic compromise, or electrical instability 4, 1, 2.