What is the full workup and management for Non-ST-Elevation Myocardial Infarction (NSTEMI)?

NSTEMI: Complete Workup and Management

Initial Evaluation and Diagnosis

Obtain a 12-lead ECG within 10 minutes of first medical contact and have it interpreted immediately by an experienced physician. 1

Diagnostic Workup

• Measure high-sensitivity cardiac troponin (hs-cTnT) at presentation (0h) and 1 hour later using the ESC 0h/1h algorithm for rapid diagnosis and risk stratification 1
• If initial troponin measurements are inconclusive but clinical suspicion remains high, obtain an additional measurement at 3 hours 1
• Obtain additional 12-lead ECGs with recurrent symptoms or if initial ECG is non-diagnostic 1
• Perform echocardiography to assess left ventricular regional and global function 1
• Look specifically for ST-segment depression, transient ST-elevation, or T-wave inversions on ECG 2

Risk Stratification

• Calculate TIMI Risk Score (age ≥65 years, ≥3 coronary risk factors, prior coronary stenosis, ST-segment deviation, ≥2 angina episodes in 24h, aspirin use within 7 days, elevated cardiac markers): scores range from 5% risk (0-1 points) to 41% risk (6-7 points) 2
• Calculate GRACE score, with scores >140 identifying high-risk patients requiring early invasive strategy 3
• hs-cTnT >50 ng/L identifies 61.7% of NSTEMI patients and predicts 1-year mortality 3

Immediate Management

Administer aspirin 162-325 mg immediately upon presentation, then admit to a monitored unit with continuous rhythm monitoring for at least 24 hours. 4, 5

Symptomatic Treatment

• Administer supplemental oxygen only if arterial oxygen saturation is <90% 4, 5
• Give sublingual or intravenous nitroglycerin for ongoing ischemic symptoms unless contraindicated (systolic BP <90 mmHg, severe bradycardia, tachycardia without heart failure, right ventricular infarction, or phosphodiesterase inhibitor use within 24-48 hours) 4
• Consider morphine sulfate intravenously for uncontrolled chest discomfort despite nitroglycerin 5
• Initiate beta-blockers to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility 4, 5

Antiplatelet Therapy

Continue aspirin 75-162 mg daily indefinitely (Level of Evidence: A). 2, 4, 1, 5

P2Y12 Inhibitor Selection

Add a P2Y12 receptor inhibitor to aspirin for 12 months unless contraindicated or at high bleeding risk. 4, 1

The choice depends on your management strategy:

• Ticagrelor (loading dose 180 mg, then 90 mg twice daily) is preferred regardless of invasive or conservative strategy 1
• Prasugrel (loading dose 60 mg, then 10 mg daily; 5 mg daily if age ≥75 years or weight <60 kg) is appropriate for P2Y12 inhibitor-naive patients undergoing PCI, but is contraindicated in patients with prior stroke or TIA 2, 1, 6
• Clopidogrel (loading dose 300-600 mg, then 75 mg daily) should only be used when prasugrel or ticagrelor are unavailable, not tolerated, or contraindicated 2, 1

Important: When using ticagrelor, aspirin dose must not exceed 100 mg daily 6

GP IIb/IIIa Inhibitors

• Do not routinely use GP IIb/IIIa inhibitors upstream (before angiography) as early routine eptifibatide showed no benefit over delayed provisional use and increased major bleeding (2.6% vs 1.8%, P=0.02) 2
• Consider provisional use at time of PCI in high-risk patients (elevated troponin, diabetes) undergoing revascularization 2

Anticoagulant Therapy

Administer parenteral anticoagulation to all NSTEMI patients in addition to antiplatelet therapy. 4, 1, 5

Anticoagulant Options

Choose one of the following:

• Unfractionated heparin (UFH): Continue for at least 48 hours or until discharge if given before angiography (Level of Evidence: A) 2, 1, 5
• Enoxaparin: Continue for duration of hospitalization, up to 8 days (Level of Evidence: A) 2, 1, 5
• Fondaparinux: Continue for duration of hospitalization, up to 8 days (Level of Evidence: B) 2, 1, 5
• Bivalirudin: Alternative option 1, 5

Management Strategy Selection

Choose early invasive strategy (angiography within 24-48 hours) for patients with any of the following high-risk features: 4, 1, 5

• Refractory angina despite medical therapy
• Hemodynamic instability
• Electrical instability (ventricular arrhythmias)
• Elevated cardiac biomarkers (especially hs-cTnT >50 ng/L)
• GRACE score >140 or TIMI risk score ≥7
• HEART score ≥7 3

Select conservative strategy with stress testing for low-risk patients (TIMI score 0-1, stable hemodynamics, normal troponin) or those with significant comorbidities where invasive risks outweigh benefits 2, 4, 1, 5

Post-Angiography Management

If PCI is Selected

• Continue aspirin indefinitely (Level of Evidence: A) 2, 1, 5
• Administer P2Y12 inhibitor loading dose if not given before angiography (Level of Evidence: A) 2, 1, 5
• Continue dual antiplatelet therapy for 12 months 4, 1

If CABG is Selected

• Continue aspirin (Level of Evidence: A) 2, 1, 5
• Stop clopidogrel 5-7 days before elective CABG (Level of Evidence: B) 2, 1, 5
• Stop prasugrel at least 7 days before surgery 1
• Stop ticagrelor at least 5 days before surgery 1
• Discontinue GP IIb/IIIa inhibitors (eptifibatide or tirofiban) 4 hours before CABG 2
• Discontinue enoxaparin 12-24 hours before CABG and transition to UFH 2
• Discontinue fondaparinux 24 hours before CABG and transition to UFH 2

If Conservative Strategy After Angiography

• Continue aspirin (Level of Evidence: A) 5
• Administer clopidogrel loading dose if not given before angiography (Level of Evidence: A/B) 5

Conservative Strategy Stress Testing

For patients managed conservatively without high-risk features requiring angiography, perform stress testing before discharge. 2

• If stress test shows high-risk features, proceed to diagnostic angiography (Level of Evidence: A) 2
• If stress test shows low risk, prepare for discharge with: 2
  • Continue aspirin indefinitely (Level of Evidence: A)
  • Continue clopidogrel for at least 1 month (Level of Evidence: B) and ideally up to 1 year
  • Discontinue GP IIb/IIIa inhibitor if started (Level of Evidence: A)
  • Continue anticoagulation as outlined above, then discontinue

Long-Term Management and Secondary Prevention

Measure left ventricular ejection fraction (LVEF) in all patients. 1, 5

Based on LVEF Results

• If LVEF ≤0.40, consider diagnostic angiography (Level of Evidence: B) 1, 5
• If LVEF >0.40, consider stress testing (Level of Evidence: B) 1, 5

Medical Therapy

• Initiate ACE inhibitors for patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes 4, 1, 5
• Consider ARBs for ACE inhibitor-intolerant patients 4, 1, 5
• Initiate beta-blockers for all NSTEMI patients without contraindications 1, 5
• Initiate high-intensity statin therapy regardless of baseline LDL levels 5

Critical Contraindications and Pitfalls

Avoid NSAIDs (except aspirin) during hospitalization as they increase mortality, reinfarction, hypertension, heart failure, and myocardial rupture risk 4, 5

Do not administer immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 4, 5

Avoid intravenous ACE inhibitors within the first 24 hours due to increased hypotension risk 5

Do not use prasugrel in patients with prior stroke or TIA as it increases fatal bleeding risk (0.4% vs 0.1%, P=0.002) 2, 6

Recognize that prasugrel increases TIMI major bleeding (2.4% vs 1.8% with clopidogrel, HR 1.32, P=0.03) despite reducing stent thrombosis 2

When loading P2Y12 inhibitors upstream (>4 hours before angiography), median time to angiography is approximately 17 hours, which is safe with very low bleeding rates (0.24% TIMI major bleeding) 7