What are the guidelines for managing Non-ST-Elevation Myocardial Infarction (NSTEMI) in patients with Cardiovascular Disease (CVD)?

NSTEMI Management Guidelines

Immediate Management (First 24 Hours)

Administer aspirin 162-325 mg immediately upon presentation (non-enteric formulation, chewed or taken orally), followed by maintenance dosing of 75-100 mg daily indefinitely. 1, 2, 3 This remains the cornerstone of NSTEMI therapy regardless of bleeding risk.

Initial Stabilization

• Admit to a monitored unit with continuous rhythm monitoring for at least 24 hours (or until PCI, whichever comes first) to detect life-threatening arrhythmias 1, 2, 3

• Administer supplemental oxygen only if arterial oxygen saturation is <90% or if respiratory distress is present 1, 3

• Give nitroglycerin 0.4 mg sublingually every 5 minutes for up to 3 doses for ongoing chest pain, then assess need for IV nitroglycerin 1, 3

  • Contraindications: systolic BP <90 mmHg, severe bradycardia, right ventricular infarction, or phosphodiesterase inhibitor use within 24 hours (sildenafil) or 48 hours (tadalafil) 1, 3

• Consider morphine sulfate IV for uncontrolled ischemic chest pain despite nitroglycerin, though use cautiously as it may delay antiplatelet absorption 2, 3

Anti-Ischemic Therapy

• Initiate oral beta-blockers within 24 hours unless contraindicated (heart failure signs, low-output state, PR interval >0.24 seconds, second or third-degree heart block, active asthma) 1, 3

  • Do NOT give IV beta-blockers to patients with heart failure signs or cardiogenic shock risk factors 1

• Start ACE inhibitors within 24 hours for patients with anterior MI, heart failure, pulmonary congestion, or LVEF ≤0.40, unless hypotensive (systolic BP <100 mmHg or >30 mmHg below baseline) 1, 3

  • Avoid IV ACE inhibitors within first 24 hours due to hypotension risk 1, 3

• Use ARBs for ACE inhibitor-intolerant patients with heart failure or LVEF ≤0.40 1, 2

Anticoagulation Strategy

Choose one anticoagulant based on bleeding risk and institutional protocols: 2, 3

• Unfractionated heparin (UFH): Preferred for high bleeding risk due to short half-life and reversibility; continue for at least 48 hours or until discharge 1, 2, 3

• Enoxaparin: 1 mg/kg subcutaneously every 12 hours; continue for duration of hospitalization up to 8 days 1, 2, 3

• Fondaparinux: Continue for duration of hospitalization up to 8 days 1, 2

Risk Stratification and Timing of Invasive Strategy

Very High-Risk Features (Immediate Angiography <2 Hours)

Proceed immediately to cardiac catheterization if any of the following are present: 1, 2, 3

• Hemodynamic instability or cardiogenic shock
• Recurrent or refractory angina despite intensive medical therapy
• Life-threatening ventricular arrhythmias or cardiac arrest
• Mechanical complications (acute mitral regurgitation, ventricular septal defect)
• Acute heart failure with ongoing ischemia
• Recurrent dynamic ST-segment changes (≥0.05 mV depression)

High-Risk Features (Early Angiography Within 24 Hours)

Perform early invasive strategy (angiography within 24 hours) for patients with: 1, 2, 3

• Elevated cardiac biomarkers (high-sensitivity troponin)
• Dynamic ST-segment or T-wave changes
• GRACE risk score >140 or high TIMI risk score
• Diabetes mellitus
• Renal insufficiency (eGFR <60 mL/min/1.73m²)
• LVEF <40%
• Recent PCI or prior CABG
• Recurrent angina or ischemia at rest or with low-level activity

Conservative Strategy

Consider conservative (selectively invasive) strategy for: 1

• Lower-risk patients without ongoing ischemia
• Patients with extensive comorbidities (liver failure, pulmonary failure, cancer) where revascularization risks outweigh benefits
• Patients with low GRACE or TIMI risk scores and normal troponin

Antiplatelet Therapy Strategy

Timing of P2Y12 Inhibitor Loading

For UA/NSTEMI patients, delay P2Y12 inhibitor loading dose until coronary anatomy is established at angiography to avoid increased bleeding risk if urgent CABG is needed 4

• In a trial of 4,033 NSTEMI patients, no clear benefit was observed when prasugrel loading dose was administered prior to diagnostic angiography compared to at time of PCI, but bleeding risk was increased with early administration 4

Post-Angiography Antiplatelet Regimen

If PCI is performed: 2, 3

• Continue aspirin 75-100 mg daily indefinitely
• Add P2Y12 inhibitor loading dose if not given before angiography:
  • Ticagrelor 180 mg loading, then 90 mg twice daily (preferred) 1, 2
  • Prasugrel 60 mg loading, then 10 mg daily (avoid if age ≥75 years, weight <60 kg, or history of stroke/TIA) 4
  • Clopidogrel 600 mg loading, then 75 mg daily (if ticagrelor or prasugrel contraindicated) 2
• Continue dual antiplatelet therapy for 12 months unless excessive bleeding risk 2, 3

If CABG is selected: 2

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

If medical therapy only: 2

• Continue aspirin indefinitely
• Add clopidogrel 75 mg daily if not given before angiography

Critical Medications to Avoid

Do NOT administer the following during hospitalization: 1, 2, 3

• NSAIDs (except aspirin) - increase risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture 1, 2, 3
• Immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 1, 3
• IV ACE inhibitors within first 24 hours due to hypotension risk 1, 3
• IV beta-blockers in patients with heart failure signs or cardiogenic shock risk factors 1

Hospital Discharge and Long-Term Management

Discharge Medications

All patients should be discharged on: 1, 2, 3

• Aspirin 75-100 mg daily indefinitely
• P2Y12 inhibitor for 12 months (if PCI performed or high-risk features)
• Beta-blocker (unless contraindicated)
• ACE inhibitor or ARB (if heart failure, LVEF <0.40, hypertension, or diabetes)
• High-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) regardless of baseline LDL levels 2, 3
• Sublingual or spray nitroglycerin with instructions for use 1, 3

Patient Education

Before discharge, instruct patients: 1

• If chest pain lasts >2-3 minutes, stop activity and take 1 dose of sublingual nitroglycerin
• If pain is unimproved or worsening 5 minutes after nitroglycerin, call 9-1-1 immediately
• May take additional nitroglycerin at 5-minute intervals (2 more times) while waiting for EMS
• Contact physician without delay if anginal pattern changes (more frequent, severe, or occurs at rest)

Follow-Up Assessment

Measure LVEF before discharge: 2

• If LVEF ≤0.40, consider diagnostic angiography if not already performed
• If LVEF >0.40, consider stress test for risk stratification

Continue aggressive risk factor modification: 1

• Smoking cessation
• Blood pressure control
• Diabetes management
• Lipid management with high-intensity statin
• Cardiac rehabilitation referral