What is the management and classification of Non-ST-Elevation Myocardial Infarction (NSTEMI) in the context of Acute Coronary Syndrome (ACS)?

NSTEMI Classification and Management in Acute Coronary Syndrome

NSTEMI is classified as a distinct entity within the Acute Coronary Syndrome (ACS) spectrum, characterized by myocardial ischemia with evidence of myocardial necrosis without ST-segment elevation on ECG. 1

Classification of ACS

ACS encompasses three distinct clinical conditions:

1. Unstable Angina (UA):

   • Characterized by ischemic chest pain without myocardial necrosis
   • Normal cardiac biomarkers (troponin)
   • May show transient ST-segment depression or T-wave changes on ECG

2. Non-ST-Elevation Myocardial Infarction (NSTEMI):

   • Elevated cardiac biomarkers (troponin)
   • ST-segment depression, T-wave inversion, or normal ECG
   • Partially occlusive coronary thrombus causing subendocardial necrosis

3. ST-Elevation Myocardial Infarction (STEMI):

   • Elevated cardiac biomarkers
   • Persistent ST-segment elevation on ECG
   • Completely occlusive coronary thrombus causing transmural necrosis

The distinction between UA and NSTEMI is primarily based on whether ischemia is severe enough to cause myocardial damage with detectable quantities of cardiac injury biomarkers, most commonly troponin. 2

Pathophysiology

The most common cause of NSTEMI is reduced myocardial perfusion due to:

• Coronary artery narrowing from a non-occlusive thrombus developed on a disrupted atherosclerotic plaque
• Abnormal constriction of coronary arteries
• Less common causes include coronary artery spasm, embolism, and dissection 2, 1

Diagnosis of NSTEMI

Diagnosis requires integration of:

1. Clinical presentation: Chest pain/discomfort at rest or with minimal exertion lasting >20 minutes
2. ECG findings: New horizontal or down-sloping ST-segment depression ≥0.5 mm in ≥2 contiguous leads and/or T-wave inversion >1 mm in ≥2 contiguous leads
3. Cardiac biomarkers: Elevated cardiac troponin (cTn) levels 1

With the increasing sensitivity of troponin assays, biomarker-negative ACS (i.e., UA) is becoming rarer. 2

Risk Stratification

Risk stratification is essential for determining management strategy:

• High-risk features: Recurrent angina, hemodynamic instability, heart failure, life-threatening arrhythmias, dynamic ST-segment changes
• Risk assessment tools: TIMI, PURSUIT, GRACE, and NCDR-ACTION scores help predict outcomes 2

Management of NSTEMI

Immediate Management

1. Anti-ischemic therapy:

   • Oxygen if saturation <90%
   • Nitrates for ongoing chest pain
   • Beta-blockers (in absence of contraindications)
   • Morphine for pain relief if needed 2

2. Antithrombotic therapy:

   • Antiplatelet therapy:
     • Aspirin (75-325 mg daily)
     • P2Y12 inhibitor (clopidogrel 300 mg loading dose followed by 75 mg daily) 3
   • Anticoagulation:
     • Unfractionated heparin or low-molecular-weight heparin

Invasive vs. Conservative Strategy

Early invasive strategy (within 24-72 hours) is recommended for patients with:

• Hemodynamic instability
• Recurrent or ongoing chest pain despite medical therapy
• Dynamic ST-T wave changes
• High-risk features on risk scores
• Elevated cardiac biomarkers 2

Ischemia-guided strategy (previously called conservative strategy) may be considered for low-risk patients without recurrent symptoms 2

Long-term Management

1. Secondary prevention medications:

   • Antiplatelet therapy (aspirin indefinitely, P2Y12 inhibitor for up to 12 months)
   • Statins (high-intensity)
   • Beta-blockers
   • ACE inhibitors (especially with reduced ejection fraction, hypertension, or diabetes)

2. Risk factor modification:

   • Smoking cessation
   • Blood pressure control
   • Diabetes management
   • Regular physical activity
   • Dietary modifications 2

Clinical Outcomes

The CURE study demonstrated that in patients with NSTE-ACS, the addition of clopidogrel to aspirin resulted in a 20% relative risk reduction in cardiovascular death, MI, or stroke compared to aspirin alone. 3

Important Distinctions

Feature	Unstable Angina	NSTEMI	STEMI
ECG Changes	Transient ST depression or T-wave changes	ST depression, T-wave inversion	ST-segment elevation
Cardiac Biomarkers	Normal	Elevated	Elevated
Coronary Occlusion	Non-occlusive thrombus	Partially occlusive thrombus	Completely occlusive thrombus
Myocardial Damage	No myonecrosis	Subendocardial necrosis	Transmural necrosis
Mortality Risk	Lower	Intermediate	Higher

Pitfalls to Avoid

1. Delayed diagnosis: With high-sensitivity troponin assays, serial measurements may be necessary to detect rising values
2. Overlooking NSTEMI in patients with atypical presentations: Especially in women, elderly, and diabetic patients
3. Inappropriate risk stratification: Failure to identify high-risk patients who would benefit from early invasive strategy
4. Underutilization of guideline-directed medical therapy: All eligible patients should receive dual antiplatelet therapy, statins, and other secondary prevention medications
5. Ignoring type 2 MI: NSTEMI can result from oxygen supply-demand mismatch without plaque rupture (e.g., severe anemia, tachyarrhythmias) 2, 1