What are the categories of Acute Coronary Syndrome (ACS) and their respective treatments?

Categories of Acute Coronary Syndrome

Acute Coronary Syndrome encompasses three distinct clinical entities that exist along a continuum of severity: Unstable Angina (UA), Non-ST-Segment Elevation Myocardial Infarction (NSTEMI), and ST-Segment Elevation Myocardial Infarction (STEMI), with classification based on ECG findings and cardiac troponin levels. 1

Classification Framework

The initial diagnosis and classification should be based on three key elements: clinical history and symptomatology, 12-lead ECG interpretation (obtained within 10 minutes of presentation), and cardiac troponin assessment. 1

1. Unstable Angina (UA)

• Definition: Transient myocardial ischemia leading to diminished coronary flow in the absence of significant myonecrosis, with cardiac troponin levels remaining below the 99th percentile upper reference limit. 1

• Clinical presentations include: 1

  • Prolonged anginal pain at rest (>20 minutes)
  • New onset (de novo) angina of at least Canadian Cardiovascular Society Class II or III severity
  • Recent destabilization of previously stable angina with crescendo pattern (Class III characteristics)
  • Post-MI angina

• ECG findings: May show transient ST-segment depression, T-wave inversion, flat T waves, pseudo-normalization of T waves, or may be completely normal. 1

• Diagnostic note: With high-sensitivity cardiac troponin assays, the diagnosis of unstable angina has decreased by approximately 4% absolute (20% relative), with a reciprocal increase in NSTEMI detection. 1

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

• Definition: More prolonged or severe myocardial ischemia resulting in myocardial necrosis with elevated cardiac biomarkers (high-sensitivity cardiac troponin above the 99th percentile), typically from a partially occluded coronary artery causing subendocardial ischemia. 1

• ECG findings: 1, 2

  • ST-segment depression (approximately 31% of cases)
  • T-wave inversions (approximately 12% of cases)
  • Combined ST-segment depression with T-wave inversions (16% of cases)
  • No significant ECG changes (approximately 41% of cases)
  • Transient ST-segment elevation may occur

• Clinical spectrum: Ranges from asymptomatic patients to those with ongoing ischemia, electrical or hemodynamic instability, or cardiac arrest. 1

3. ST-Segment Elevation Myocardial Infarction (STEMI)

• Definition: Complete coronary artery occlusion leading to transmural myocardial ischemia and infarction, with persistent ST-segment elevation (>20 minutes) on ECG and elevated cardiac troponin. 1, 2

• ECG criteria: Persistent ST-segment elevation ≥1 mm in two contiguous leads. 3, 2

• Prevalence: Accounts for approximately 30% of all ACS cases. 3, 2

Pathophysiological Mechanism

All three categories typically result from atherosclerotic plaque disruption (rupture or erosion) with associated partial or complete coronary artery thrombosis and/or microemboli, classified as Type 1 MI under the Universal Definition of MI. 1 Progressive lipid accumulation and inflammation within the plaque leads to instability, with subsequent exposure of plaque contents to circulation, activating the coagulation cascade and culminating in thrombosis. 1

Critical Clinical Consideration

The pathophysiology of ACS is dynamic—patients can rapidly progress from one clinical condition (UA → NSTEMI → STEMI) to another during presentation and initial evaluation, requiring continuous monitoring and serial assessments. 1, 4

Treatment Approach by Category

STEMI Management

• Immediate reperfusion is paramount: Primary percutaneous coronary intervention (PCI) within 120 minutes reduces mortality from 9% to 7%. 2

• If PCI within 120 minutes is not possible: Administer fibrinolytic therapy (alteplase, reteplase, or tenecteplase at full dose for patients <75 years; half dose for ≥75 years), followed by transfer for PCI within 24 hours. 2

• Adjunctive therapy: 3, 5

  • Dual antiplatelet therapy: Aspirin 75-325 mg daily plus clopidogrel (300 mg loading dose, then 75 mg daily) for 12 months
  • Anticoagulation with low-molecular-weight heparin or unfractionated heparin
  • Beta-blockers (oral or IV unless contraindicated)
  • High-intensity statins immediately (target LDL <70 mg/dL)
  • ACE inhibitors for LVEF <40%, diabetes, hypertension, or chronic kidney disease

NSTEMI/Unstable Angina Management

• Risk stratification determines timing of invasive strategy: High-risk patients with NSTE-ACS benefit from coronary angiography and revascularization within 24-48 hours, reducing mortality from 6.5% to 4.9%. 2

• High-risk features warranting immediate angiography: 1

  • Recurrent or ongoing chest pain
  • Marked ST-segment depression on ECG
  • Heart failure
  • Hemodynamic or electrical instability

• Pharmacological management: 1, 3, 5

  • Dual antiplatelet therapy: Aspirin 75-150 mg daily indefinitely plus P2Y12 inhibitor (clopidogrel 300 mg loading, then 75 mg daily) for 12 months
  • Anticoagulation during acute phase
  • Nitrates (oral or IV) for persistent/recurrent chest pain
  • Beta-blockers unless contraindicated
  • High-intensity statins
  • ACE inhibitors for appropriate indications

• Important distinction: Compared to NSTEMI patients, those with unstable angina have substantially lower risk of death and derive less benefit from intensified antiplatelet therapy and early invasive strategy. 1

Common Pitfalls to Avoid

• Do not dismiss ACS based on normal ECG: A normal ECG does not exclude ACS, particularly in NSTE-ACS where approximately 41% have no significant ECG changes. 1, 4

• Recognize atypical presentations: Approximately 40% of men and 48% of women present with nonspecific symptoms such as isolated dyspnea, more common in elderly, diabetics, and women. 3, 2

• CYP2C19 poor metabolizers: Approximately 2% of White, 4% of Black, and 14% of Chinese patients are poor metabolizers of clopidogrel, requiring consideration of alternative P2Y12 inhibitors. 5

• Avoid concomitant omeprazole or esomeprazole with clopidogrel: These significantly reduce clopidogrel's antiplatelet activity. 5