How should unstable angina be evaluated and treated in the acute setting?

Evaluation and Treatment of Unstable Angina in the Acute Setting

Patients presenting with unstable angina require immediate hospitalization with aspirin 162-325 mg, anticoagulation (enoxaparin, fondaparinux, or unfractionated heparin), clopidogrel loading (300-600 mg), continuous ECG monitoring, and urgent risk stratification to determine whether early invasive coronary angiography (within 24-48 hours) or initial conservative management is indicated. 1, 2, 3

Immediate Recognition and Initial Management

Clinical Presentation

Unstable angina presents in three distinct patterns that distinguish it from stable angina: 4

• Rest angina: Chest pain occurring at rest, lasting up to 20 minutes
• Crescendo angina: Previously stable angina that rapidly increases in severity, frequency, or occurs at lower thresholds over ≤4 weeks
• New-onset severe angina: Recent onset causing marked limitation of ordinary activity within 2 months of presentation

First 10 Minutes

Obtain a 12-lead ECG within 10 minutes of presentation to identify ST-segment depression, T-wave inversions, or other ischemic changes—persistent ST-elevation indicates STEMI requiring different management. 3, 4

Administer aspirin 162-325 mg immediately (chewable preferred for faster absorption) unless contraindicated, as this significantly reduces cardiovascular events and should continue indefinitely. 1, 2

Place patient on continuous multi-lead ECG monitoring to detect ongoing ischemia, arrhythmias, and sudden ventricular fibrillation, which is the major preventable cause of early death. 2, 3

Initial Pharmacologic Therapy (First Hour)

Antiplatelet therapy:

• Aspirin 162-325 mg (already given)
• Clopidogrel 300-600 mg loading dose followed by 75 mg daily for 12 months 1, 2

Anticoagulation (select one): 1, 2

• Enoxaparin 1 mg/kg subcutaneously every 12 hours (preferred for conservative management, lower risk of heparin-induced thrombocytopenia)
• Fondaparinux 2.5 mg subcutaneously once daily (associated with less bleeding than enoxaparin)
• Unfractionated heparin (if early invasive strategy planned or renal dysfunction present)

Anti-ischemic therapy:

• Sublingual nitroglycerin 0.4 mg every 5 minutes for up to 3 doses for immediate symptom relief 2
• Intravenous nitroglycerin starting at 5-10 mcg/min if ongoing ischemia or hypertension, titrate by 10 mcg/min every 3-5 minutes 2
• Oral beta-blocker promptly in all patients without contraindications (heart failure, bradycardia, hypotension), targeting heart rate 50-60 bpm 2

Supplemental oxygen only if arterial oxygen saturation <90% by pulse oximetry. 2

Risk Stratification (First 6-12 Hours)

High-Risk Features Requiring Early Invasive Strategy

Patients with ANY of the following require coronary angiography within 24-48 hours: 1, 2, 3

• Recurrent ischemia (chest pain or dynamic ST-segment changes) despite medical therapy
• Elevated cardiac troponin levels
• Hemodynamic instability (hypotension, pulmonary edema)
• Major arrhythmias (sustained ventricular tachycardia or ventricular fibrillation)
• Early post-infarction unstable angina
• Prior coronary artery bypass graft surgery
• Diabetes mellitus with other high-risk features

TIMI Risk Score Application

Calculate the 7-point TIMI Risk Score to quantify risk, assigning one point for each: 3

• Age ≥65 years
• ≥3 coronary risk factors (hypertension, diabetes, smoking, family history, hyperlipidemia)
• Prior angiographic coronary obstruction ≥50%
• ST-segment deviation on presenting ECG
• ≥2 angina events within 24 hours
• Aspirin use within 7 days
• Elevated cardiac markers

Risk stratification by score: 3

• Score 0-1: 5% risk of death/MI/severe ischemia (low risk)
• Score 2: Intermediate risk
• Score 6-7: 41% risk (very high risk)

Serial Monitoring

Measure cardiac troponin at presentation and repeat every 6-12 hours to detect evolving myocardial necrosis. 2, 3

Repeat ECG promptly if recurrent chest pain occurs during observation. 1

Management Strategy Based on Risk

High-Risk Patients: Early Invasive Strategy

Add glycoprotein IIb/IIIa inhibitor (eptifibatide, abciximab, or tirofiban) while preparing for angiography, continuing heparin concurrently. 4, 1

Perform coronary angiography: 1

• Immediately for major arrhythmias, hemodynamic instability, or refractory ischemia
• Within 24-48 hours for other high-risk patients

Revascularization strategy based on coronary anatomy: 1

• Single-vessel disease: Percutaneous coronary intervention (PCI) of culprit lesion preferred
• Left main or triple-vessel disease with LV dysfunction: Coronary artery bypass grafting (CABG) recommended
• Multivessel disease with diabetes: CABG with internal mammary arteries preferred over PCI 1

Post-PCI management:

• Continue aspirin indefinitely 1
• Discontinue GP IIb/IIIa blocker 12-24 hours after PCI 1
• Continue clopidogrel 75 mg daily for 12 months 1

For CABG:

• Continue aspirin perioperatively 1
• Discontinue clopidogrel 5-7 days before elective CABG 1

Intermediate/Low-Risk Patients: Conservative Strategy

Continue medical therapy with aspirin, clopidogrel, anticoagulation, beta-blockers, and nitrates as needed. 4

Assess left ventricular function with echocardiography if not already performed. 3

Perform stress testing after 24-48 hours of stability to assess for inducible ischemia and guide need for angiography. 4, 5

Selective angiography if stress test positive, symptoms recur, or LV dysfunction identified. 3

Additional Therapies for Mortality Reduction

Initiate high-intensity statin therapy (atorvastatin 80 mg daily) within 24-96 hours regardless of baseline LDL cholesterol, targeting LDL <100 mg/dL. 1, 2

Start ACE inhibitor if patient has anterior MI, persistent hypertension, LV dysfunction (ejection fraction <40%), heart failure, or diabetes. 2

Critical Pitfalls to Avoid

Never administer fibrinolytic therapy to patients with unstable angina/NSTEMI without ST-segment elevation—it is contraindicated and may be harmful. 4, 1

Do not delay treatment while waiting for cardiac biomarker results in high-risk patients; initiate antiplatelet and anticoagulation therapy immediately based on clinical presentation and ECG findings. 1

Do not discharge patients prematurely—even those initially appearing low-risk require 8-12 hours of observation with serial troponins and ECGs before safe discharge can be considered. 1

Avoid beta-blockers in patients with active heart failure, significant bradycardia (<50 bpm), hypotension, or severe reactive airway disease. 2

Monitor for heparin-induced thrombocytopenia with platelet counts if unfractionated heparin used beyond 5-7 days; enoxaparin has lower risk. 2