In an adult with chest pain, what ECG criteria define a non‑ST‑segment‑elevation myocardial infarction and what is the recommended immediate management, including aspirin, a P2Y12 inhibitor (clopidogrel or ticagrelor), anticoagulation (unfractionated heparin or enoxaparin), nitroglycerin, β‑blocker, high‑intensity statin, risk stratification (TIMI or GRACE) and early invasive strategy?

NSTEMI ECG Criteria and Immediate Management

ECG Criteria for NSTEMI

NSTEMI is diagnosed by the absence of ST-segment elevation on ECG, but patients typically present with nonspecific ECG changes including ST-segment depression, T-wave inversions, or even a completely normal ECG in up to 55% of cases initially. 1

• ST-segment depression is the most common finding, particularly in inferior and lateral leads, indicating high-risk disease 2
• T-wave inversions may be present, though these are nonspecific 1
• Normal or nondiagnostic ECG occurs in a substantial proportion of patients, making serial ECGs essential 1
• Repeat ECGs every 15-30 minutes during the first hour are recommended for symptomatic patients with initially nondiagnostic findings, as ST-segment changes are frequently unstable and dynamic in early ACS 1, 2

The diagnosis is confirmed by elevated cardiac troponin levels with a rising and/or falling pattern, measured at presentation and 3-6 hours after symptom onset 1

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Immediate Medical Management

Antiplatelet Therapy

Aspirin 162-325 mg non-enteric coated (chewed) should be administered immediately upon presentation, followed by 81 mg daily indefinitely, providing a 23% relative risk reduction in 5-week vascular mortality. 3, 2

• P2Y12 inhibitor loading dose should be given as soon as possible: 3, 4
  • Ticagrelor 180 mg (preferred in high-risk patients) 3, 2
  • Clopidogrel 300-600 mg (300 mg standard, 600 mg if proceeding to PCI within 2 hours) 3, 4
• Maintenance dosing: ticagrelor 90 mg twice daily or clopidogrel 75 mg daily for minimum 9-12 months 3
• This dual antiplatelet therapy provides a 20% relative risk reduction in CV death, MI, or stroke 3

Anticoagulation

Low molecular weight heparin (LMWH) is preferred over unfractionated heparin and should be initiated immediately, continuing until PCI or for the duration of hospitalization if managed medically. 1, 3, 4

• Enoxaparin 1 mg/kg subcutaneously every 12 hours is the preferred LMWH regimen 2, 4
• Unfractionated heparin (UFH) alternative: 60-70 U/kg bolus (maximum 5000 U) followed by 12-15 U/kg/h infusion targeting aPTT 50-70 seconds (1.5-2.0 times control) 2, 4
• Fondaparinux is recommended over enoxaparin for early conservative or delayed invasive strategies 4

Anti-Ischemic Therapy

Nitroglycerin sublingual should be administered for ongoing chest pain, with IV nitroglycerin for persistent ischemia, heart failure, or hypertension. 3

Beta-blockers should be initiated orally within the first 24 hours unless contraindications exist (heart failure, low-output state, risk of cardiogenic shock) 3

High-Intensity Statin

High-intensity statin therapy should be initiated immediately (though not explicitly detailed in the provided evidence, this is standard guideline-based care) 3

GP IIb/IIIa Inhibitors

Consider adding GP IIb/IIIa inhibitors (eptifibatide or tirofiban) in moderate-to-high risk patients, particularly those with elevated troponin, diabetes, or planned PCI 3, 4

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Risk Stratification

Objective risk stratification using validated scores is essential to guide treatment intensity and timing of invasive strategy. 1

• GRACE risk score >140 defines high-risk patients 1
• TIMI risk score >4 defines high-risk patients 1
• These scores predict short- and intermediate-term cardiovascular outcomes and dictate invasive strategy timing 1

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Early Invasive Strategy

High-risk NSTEMI patients (GRACE >140 or TIMI >4) should receive an early invasive strategy with diagnostic angiography within 24 hours of admission. 1, 3

• Intermediate-risk patients may receive delayed invasive strategy within 24-72 hours 1, 3
• Patients with hemodynamic instability, cardiogenic shock, refractory ischemia, or life-threatening arrhythmias require immediate invasive strategy (within 2 hours), similar to STEMI management 1
• Early invasive use has increased from 9% (1995) to 60% (2015), with corresponding mortality reduction from 17.2% to 6.3% 3

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Critical Pitfalls to Avoid

Fibrinolytic therapy is absolutely contraindicated in NSTEMI and may cause harm—never administer thrombolytics for NSTEMI. 3

Primary PCI is not indicated for NSTEMI—the appropriate approach is early invasive strategy (within 24-72 hours), not emergent catheterization as in STEMI 3

Do not delay antiplatelet and anticoagulation therapy while waiting for troponin results—initiate treatment based on clinical suspicion and ECG findings 2

Serial troponin measurement is mandatory: obtain at presentation, 3-6 hours later, and beyond 6 hours if initial values are normal but clinical suspicion remains high 1