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

Management of Non-ST-Elevation Myocardial Infarction (NSTEMI)

Immediately administer aspirin 162-325 mg (chewed or non-enteric formulation), admit to a monitored unit, initiate dual antiplatelet therapy with a P2Y12 inhibitor (preferably ticagrelor), start parenteral anticoagulation, and perform risk stratification to determine early invasive versus conservative strategy within 24-48 hours. 1, 2

Immediate Initial Management (First Hour)

• Administer aspirin 162-325 mg immediately as a non-enteric formulation, either chewed or taken orally, regardless of prior aspirin use 2
• Admit to a monitored unit with continuous cardiac rhythm monitoring for at least 24 hours to detect life-threatening arrhythmias 1, 2
• Provide supplemental oxygen only if arterial oxygen saturation is <90%—routine oxygen administration is not indicated and may be harmful 2
• Administer sublingual or intravenous nitroglycerin for ongoing ischemic chest pain, but avoid if:
  • Systolic blood pressure <90 mmHg or ≥30 mmHg below baseline
  • Severe bradycardia (<50 bpm) or tachycardia (>100 bpm without heart failure)
  • Right ventricular infarction suspected
  • Phosphodiesterase inhibitor use within 24 hours (sildenafil) or 48 hours (tadalafil) 2
• Consider morphine sulfate intravenously for uncontrolled ischemic chest discomfort despite nitroglycerin 1
• Initiate oral beta-blocker therapy (preferred over intravenous) to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility, unless contraindications exist (signs of heart failure, low-output state, cardiogenic shock risk factors) 2

Antiplatelet Therapy

Dual antiplatelet therapy is the cornerstone of NSTEMI management and must be initiated immediately. 3, 1

Aspirin

• Continue aspirin 75-162 mg daily indefinitely after the initial loading dose 1, 2
• This represents Level of Evidence A recommendation 3, 1

P2Y12 Inhibitor Selection

• Ticagrelor is the preferred P2Y12 inhibitor with a loading dose of 180 mg, then 90 mg twice daily—recommended regardless of invasive or conservative strategy 2, 4
• Prasugrel (loading dose 60 mg, maintenance 10 mg daily; 5 mg daily if ≥75 years or weight <60 kg) is appropriate for patients naive to P2Y12 inhibitors undergoing invasive coronary procedures, but contraindicated in patients with prior stroke/TIA 4
• Clopidogrel (loading dose 300-600 mg, maintenance 75 mg daily) should only be used when prasugrel or ticagrelor are not available, cannot be tolerated, or are contraindicated 4, 5
  • Critical caveat: Clopidogrel effectiveness is significantly reduced in CYP2C19 poor metabolizers (approximately 2-14% of the population); genetic testing should be considered, and alternative P2Y12 inhibitors used in poor metabolizers 5
  • Avoid concomitant use with omeprazole or esomeprazole, which significantly reduce clopidogrel's antiplatelet activity 5
• Continue P2Y12 inhibitor for 12 months unless contraindicated or high bleeding risk 2, 4

Anticoagulant Therapy

Parenteral anticoagulation must be administered to all NSTEMI patients in addition to antiplatelet therapy. 1, 2, 4

Anticoagulant Options

• Unfractionated heparin (UFH): Continue for at least 48 hours or until discharge if given before angiography (Level of Evidence: A) 3, 1
• Enoxaparin: Continue for duration of hospitalization, up to 8 days, if given before angiography (Level of Evidence: A) 3, 1
• Fondaparinux: Continue for duration of hospitalization, up to 8 days, if given before angiography (Level of Evidence: B) 3, 1
• Bivalirudin: Either discontinue or continue at 0.25 mg/kg/h for up to 72 hours at physician's discretion if given before angiography (Level of Evidence: B) 3

Special Consideration for Warfarin Patients

• Do not initiate additional anticoagulant therapy until INR is <2.0 3
• Initiate antiplatelet therapy even in therapeutically anticoagulated patients, especially if invasive strategy is planned 3

Risk Stratification and Management Strategy Selection

Risk stratification using TIMI or GRACE scores determines the timing and approach to coronary angiography. 3, 1

Early Invasive Strategy (Angiography within 24-48 hours) is indicated for:

• Refractory angina despite medical therapy 1, 2
• Hemodynamic instability or cardiogenic shock 1, 2
• Electrical instability (ventricular arrhythmias) 2
• Elevated cardiac biomarkers (troponin) 1, 2
• High GRACE or TIMI risk score (TIMI ≥3 or GRACE >140) 3, 1
• ST-segment depression on ECG 3
• Signs of heart failure 3

Conservative Strategy is appropriate for:

• Lower-risk patients (TIMI 0-1, GRACE <109) without ongoing ischemia 1, 2
• Patients with significant comorbidities where invasive risks outweigh benefits 1, 2

The TIMI Risk Score (0-7 points) includes: age ≥65 years, ≥3 coronary risk factors, prior angiographic coronary obstruction, ST-segment deviation, >2 angina events within 24 hours, aspirin use within 7 days, and elevated cardiac markers—with risk of adverse outcomes ranging from 5% (score 0-1) to 41% (score 6-7) 3

Post-Angiography Management

If Percutaneous Coronary Intervention (PCI) is Selected:

• Continue aspirin (Level of Evidence: A) 1, 2
• Administer P2Y12 inhibitor loading dose if not started before diagnostic angiography (Level of Evidence: A) 1, 2
• Discontinue intravenous GP IIb/IIIa inhibitor if started previously (Level of Evidence: B) 3

If Coronary Artery Bypass Grafting (CABG) is Selected:

• Continue aspirin (Level of Evidence: A) 1, 2
• Stop clopidogrel 5-7 days before elective CABG (Level of Evidence: B) 1, 2
• Stop prasugrel at least 7 days before surgery 4
• Stop ticagrelor at least 5 days before surgery 4

If Medical Therapy is Selected (No Revascularization):

• Continue aspirin (Level of Evidence: A) 3, 1
• Administer clopidogrel loading dose if not given before diagnostic angiography (Level of Evidence: A) 3, 1
• Discontinue intravenous GP IIb/IIIa inhibitor if started previously (Level of Evidence: B) 3
• Continue anticoagulation as outlined above 3, 1

Long-Term Management and Secondary Prevention

Cardiac Function Assessment

• Measure left ventricular ejection fraction (LVEF) in all patients (Level of Evidence: B) 1, 2
• If LVEF ≤0.40, consider diagnostic angiography if not already performed (Level of Evidence: B) 1, 2
• If LVEF >0.40, consider stress testing before discharge (Level of Evidence: B) 1

Pharmacologic Secondary Prevention

• Initiate ACE inhibitors for patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes 1, 2
• Consider ARBs for ACE inhibitor-intolerant patients 1, 2
• Continue beta-blockers indefinitely in all NSTEMI patients without contraindications 2
• Initiate high-intensity statin therapy regardless of baseline LDL levels 2

Critical Contraindications and Common Pitfalls

Absolute Contraindications

• Never administer fibrinolytic therapy in NSTEMI patients without ST-segment elevation 2
• Avoid NSAIDs (except aspirin) during hospitalization—they increase mortality, reinfarction, hypertension, heart failure, and myocardial rupture 1, 2
• Do not give immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 1, 2
• Avoid intravenous ACE inhibitors within the first 24 hours due to hypotension risk (exception: refractory hypertension) 2
• Do not administer intravenous beta blockers to patients with signs of heart failure, low-output state, or cardiogenic shock risk factors 2

Bleeding Risk Management

• P2Y12 inhibitors increase bleeding risk for the lifetime of the platelet (7-10 days) 5
• Platelet transfusions may restore hemostasis but are less effective within 4 hours of loading dose or 2 hours of maintenance dose 5
• Major bleeding occurred in 3.7% with clopidogrel versus 2.7% with placebo in the CURE trial, with increased risk if CABG performed within 5 days 3

Drug-Drug Interactions

• Avoid strong CYP2C19 inhibitors (omeprazole, esomeprazole) with clopidogrel 5
• Avoid strong CYP2C19 inducers with clopidogrel as they may potentiate bleeding risk 5