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

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

Immediate Management (First 10 Minutes)

Administer aspirin 162-325 mg (non-enteric formulation, chewed or orally) immediately upon presentation, as this is the cornerstone of NSTEMI therapy with the strongest evidence for mortality reduction. 1, 2, 3

• Place the patient in a monitored unit with continuous ECG monitoring and defibrillation capability within 10 minutes of arrival 1, 2, 3
• Administer supplemental oxygen only if arterial oxygen saturation is <90% 1, 2, 3
• Give sublingual or intravenous nitroglycerin for ongoing ischemic chest pain unless systolic blood pressure is <90 mmHg, heart rate <50 or >100 bpm without heart failure, right ventricular infarction is suspected, or phosphodiesterase inhibitors were used within 24 hours (sildenafil) or 48 hours (tadalafil) 1, 2
• Administer morphine sulfate intravenously (2-4 mg with increments of 2-4 mg at 5-15 minute intervals) only for uncontrolled ischemic chest discomfort despite nitroglycerin 3

Initial Anticoagulation (Within 30 Minutes)

Initiate parenteral anticoagulation immediately with unfractionated heparin as the preferred agent due to its short half-life and reversibility. 1, 2, 3, 4

• Unfractionated heparin: 60 units/kg IV bolus (maximum 4000 units), then 12 units/kg/hour infusion (maximum 1000 units/hour) adjusted to aPTT 1.5-2.5 times control 1
• Alternative options include enoxaparin 1 mg/kg subcutaneously every 12 hours, fondaparinux 2.5 mg subcutaneously once daily, or bivalirudin 0.1 mg/kg IV bolus then 0.25 mg/kg/hour infusion 1, 3
• Continue anticoagulation for at least 48 hours or until percutaneous coronary intervention (PCI), whichever comes first 1

Anti-Ischemic Therapy (Within 24 Hours)

Initiate oral beta-blockers within 24 hours unless contraindicated (active heart failure signs, low-output state, heart rate <60 bpm, systolic blood pressure <100 mmHg, PR interval >0.24 seconds, second or third-degree AV block, active asthma/reactive airway disease). 1, 2, 3

• Do NOT administer intravenous beta-blockers in the acute setting, as this increases the risk of cardiogenic shock. 1
• Target heart rate 50-60 bpm 1
• Metoprolol 25-50 mg orally every 6-12 hours or carvedilol 3.125-6.25 mg orally twice daily are preferred agents 1

Risk Stratification and P2Y12 Inhibitor Selection (Within 2 Hours)

Perform risk stratification using GRACE or TIMI risk scores and high-sensitivity cardiac troponin measurements to determine timing of angiography and choice of P2Y12 inhibitor. 1, 2, 3

High-Risk Features Mandating Early Invasive Strategy (Angiography Within 24 Hours):

• Recurrent angina or ischemia at rest or with low-level activity despite intensive medical therapy 1
• Elevated cardiac troponins (especially high-sensitivity troponin) 1, 2
• New or worsening ST-segment depression ≥0.05 mV 1
• Hemodynamic instability or cardiogenic shock 1, 5
• Heart failure symptoms, new S3 gallop, or new/worsening mitral regurgitation 1, 5
• Sustained ventricular tachycardia or ventricular fibrillation 1
• Left ventricular ejection fraction <0.40 1, 5
• GRACE risk score >140 1

P2Y12 Inhibitor Administration:

For patients proceeding to early invasive strategy with angiography planned within 24 hours, administer a loading dose of a P2Y12 inhibitor at the time of or immediately before PCI, NOT before diagnostic angiography. 1, 6, 7

• Ticagrelor 180 mg loading dose, then 90 mg twice daily is the preferred P2Y12 inhibitor for most patients 1, 3, 5
• Prasugrel 60 mg loading dose, then 10 mg daily is an alternative for patients undergoing PCI who do NOT have prior stroke/TIA, age ≥75 years, or weight <60 kg 1, 6
• Prasugrel is absolutely contraindicated in patients with prior stroke or TIA due to increased risk of intracranial hemorrhage 6
• Clopidogrel 300-600 mg loading dose, then 75 mg daily is reserved for patients who cannot receive ticagrelor or prasugrel 1, 7
• For patients with weight <60 kg on prasugrel, reduce maintenance dose to 5 mg daily 6

For patients managed with initial conservative strategy (no planned angiography within 24 hours), administer clopidogrel 300 mg loading dose immediately, then 75 mg daily. 1, 3

Invasive Strategy Timing

Patients with high-risk features should undergo diagnostic angiography within 24 hours of presentation, while those with ongoing refractory ischemia or hemodynamic instability require immediate angiography (<2 hours). 1, 2, 3, 5

• The TIMACS trial demonstrated that early angiography (within 24 hours) reduces ischemic complications in high-risk patients (GRACE score >140) compared to delayed angiography (>36 hours) 1
• Immediate angiography (<2 hours) is indicated for: refractory angina despite maximal medical therapy, hemodynamic instability, cardiogenic shock, life-threatening arrhythmias, or mechanical complications 1, 5
• For lower-risk patients without ongoing ischemia, angiography can be performed within 25-72 hours 1

Post-Angiography Management

If PCI Performed:

• Continue aspirin 75-162 mg daily indefinitely 1, 3
• Continue P2Y12 inhibitor (ticagrelor, prasugrel, or clopidogrel) for at least 12 months 1, 3
• Discontinue anticoagulation after uncomplicated PCI 1, 3
• If GP IIb/IIIa inhibitor (eptifibatide, tirofiban, or abciximab) was administered during PCI, discontinue after procedure completion 1

If CABG Planned:

• Continue aspirin 1
• Discontinue clopidogrel at least 5 days before elective CABG 1
• Discontinue prasugrel at least 7 days before elective CABG 1, 6
• Discontinue ticagrelor at least 5-7 days before elective CABG 1
• Discontinue GP IIb/IIIa inhibitors 4 hours before CABG 1
• Discontinue enoxaparin 12-24 hours before CABG and transition to unfractionated heparin 1
• Discontinue fondaparinux 24 hours before CABG and transition to unfractionated heparin 1

If Medical Management Selected (No Revascularization):

• Continue aspirin 75-162 mg daily indefinitely 1, 3
• Continue clopidogrel 75 mg daily or ticagrelor 90 mg twice daily for up to 12 months 1, 3
• Discontinue intravenous GP IIb/IIIa inhibitor if started 1
• Continue unfractionated heparin for 48 hours or until discharge 1
• Continue enoxaparin or fondaparinux for duration of hospitalization up to 8 days 1

Conservative Strategy for Lower-Risk Patients

For patients without high-risk features who are managed conservatively, perform non-invasive stress testing before discharge or within 72 hours. 1, 3

• If stress test reveals high-risk features (large area of ischemia, reduced ejection fraction, or inability to exercise), proceed to diagnostic angiography 1
• If stress test is low-risk, continue aspirin indefinitely and clopidogrel for at least 1 month, ideally up to 12 months 1, 3

Long-Term Medical Therapy (Initiated Before Discharge)

Initiate ACE inhibitors in all patients with heart failure, left ventricular ejection fraction <0.40, hypertension, or diabetes. 1, 3, 5

• Start with low dose (e.g., lisinopril 2.5-5 mg daily) and titrate upward 1
• Do NOT administer intravenous ACE inhibitors within the first 24 hours due to increased risk of hypotension 1, 3
• For ACE inhibitor-intolerant patients, substitute angiotensin receptor blocker (ARB) 1, 3, 5

Initiate high-intensity statin therapy regardless of baseline LDL cholesterol level. 1, 3

• Atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily 1, 3
• Target LDL cholesterol <70 mg/dL 1

Measure left ventricular ejection fraction before discharge using echocardiography. 1, 3, 5

• If LVEF ≤0.40, ensure diagnostic angiography is completed and consider aldosterone antagonist (spironolactone 12.5-25 mg daily or eplerenone 25 mg daily) if no contraindications 1, 5

Critical Contraindications and Pitfalls

NSAIDs (except aspirin) are absolutely contraindicated during hospitalization and should be avoided long-term, as they increase mortality, reinfarction, hypertension, heart failure, and myocardial rupture. 1, 3

Do NOT administer immediate-release dihydropyridine calcium channel blockers (e.g., nifedipine) without adequate beta-blockade, as this increases mortality. 1, 3

Do NOT discontinue P2Y12 inhibitor therapy prematurely (especially within the first few weeks), as this dramatically increases the risk of stent thrombosis and recurrent cardiovascular events. 6, 7

For patients requiring long-term anticoagulation (e.g., atrial fibrillation), use triple antithrombotic therapy (oral anticoagulant + aspirin + clopidogrel) for only 1 week to 1 month, then transition to dual therapy (oral anticoagulant + clopidogrel) for up to 12 months, followed by oral anticoagulant monotherapy. 4

Avoid concomitant use of clopidogrel with omeprazole or esomeprazole, as these significantly reduce clopidogrel's antiplatelet activity through CYP2C19 inhibition; use pantoprazole or other proton pump inhibitors instead if needed. 7