What is the appropriate management for a patient with suspected non‑ST‑segment elevation myocardial infarction (NSTEMI)?

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

All patients with suspected NSTEMI should receive immediate dual antiplatelet therapy with aspirin (150-300 mg loading dose, then 75-100 mg daily) plus a P2Y12 inhibitor, combined with parenteral anticoagulation, followed by risk stratification to determine timing of invasive coronary angiography. 1, 2

Initial Assessment and Diagnosis

Obtain a 12-lead ECG within 10 minutes of first medical contact and have it interpreted immediately by an experienced physician. 1, 3

• Measure high-sensitivity cardiac troponin (hs-cTn) at presentation (0 hours) and at 1 hour using the ESC 0h/1h algorithm for rapid diagnosis. 1, 3
• If the first two troponin measurements are inconclusive but clinical suspicion remains high, obtain an additional measurement at 3 hours. 1, 3
• Perform echocardiography to evaluate left ventricular regional and global function. 2, 3
• Admit all patients to a monitored unit with continuous rhythm monitoring for at least 24 hours (or until PCI, whichever comes first) even if symptoms have resolved. 4

Immediate Antiplatelet Therapy

Aspirin: Administer 150-300 mg oral loading dose (or 75-250 mg IV if unable to take oral), followed by 75-100 mg daily indefinitely. 1, 2, 3

P2Y12 Inhibitor Selection (in order of preference):

• Ticagrelor (preferred): 180 mg loading dose, then 90 mg twice daily, regardless of planned invasive or conservative strategy. 3
• Prasugrel: 60 mg loading dose, then 10 mg daily (reduce to 5 mg daily if age ≥75 years or weight <60 kg); use only in P2Y12 inhibitor-naive patients undergoing invasive procedures. 3
• Clopidogrel: 300-600 mg loading dose, then 75 mg daily; use only when ticagrelor or prasugrel are unavailable, not tolerated, or contraindicated. 3, 5

Critical caveat: Clopidogrel is less effective in CYP2C19 poor metabolizers (approximately 2-14% of patients); consider genetic testing or use alternative P2Y12 inhibitors in high-risk patients. 5

For patients requiring faster platelet inhibition: Chewing or crushing ticagrelor tablets achieves significantly better platelet inhibition at 30 minutes and 1 hour compared to swallowing whole tablets (24% greater reduction at 30 minutes, p=0.001). 6

Anticoagulation Therapy

Administer parenteral anticoagulation to all patients in addition to dual antiplatelet therapy. 2, 3

Options (listed by guideline preference):

• Fondaparinux: Preferred for patients managed conservatively due to favorable bleeding profile. 1
• Enoxaparin: Preferred over unfractionated heparin in absence of renal failure and unless CABG planned within 24 hours. 1
• Unfractionated heparin (UFH): Use when CABG likely within 24 hours due to easier reversibility. 1
• Bivalirudin: 0.75 mg/kg IV bolus followed by 1.75 mg/kg/h infusion; recommended as alternative to UFH plus GP IIb/IIIa inhibitors during PCI. 1

Duration of anticoagulation for medically managed patients:

• UFH: Continue for at least 48 hours or until discharge. 1, 3
• Enoxaparin or fondaparinux: Continue for duration of hospitalization, up to 8 days. 1, 3

Risk Stratification and Timing of Invasive Strategy

Use GRACE risk score for prognostic assessment. 1

Early invasive strategy (angiography within 24 hours) is indicated for patients with ANY of the following: 2, 3

• Refractory angina despite medical therapy
• Hemodynamic instability or cardiogenic shock
• Life-threatening arrhythmias or cardiac arrest
• Mechanical complications of MI
• Recurrent or ongoing chest pain with ST-segment changes
• Elevated cardiac troponin (especially if rising pattern)
• GRACE score indicating high risk

Conservative strategy may be considered for: 2

• Low-risk patients (low GRACE score) without ongoing ischemia
• Patients with significant comorbidities where invasive risks outweigh benefits
• Patients with no significant obstructive CAD on prior imaging

Important pitfall: The EARLY ACS trial demonstrated that routine upstream GP IIb/IIIa inhibitor therapy (before angiography) does not reduce ischemic events compared to provisional use at time of PCI, but increases major bleeding (2.6% vs 1.8%, p=0.02). 1 Therefore, defer GP IIb/IIIa inhibitors until angiography unless patient has refractory ischemia.

Post-Angiography Management

If PCI is performed:

• Continue aspirin indefinitely. 1, 2
• Administer P2Y12 inhibitor loading dose if not given before angiography. 1, 3
• Continue P2Y12 inhibitor for at least 12 months. 2, 3
• Discontinue anticoagulation after uncomplicated PCI. 1

If CABG is planned:

• Continue aspirin. 1, 2
• Stop clopidogrel 5-7 days before surgery. 1, 3
• Stop prasugrel at least 7 days before surgery. 3
• Stop ticagrelor at least 5 days before surgery. 3
• Discontinue bivalirudin 3 hours before CABG and use UFH per institutional practice. 1

If medical management is selected:

• Continue aspirin indefinitely. 1
• Administer P2Y12 inhibitor loading dose if not given before angiography. 1
• Discontinue GP IIb/IIIa inhibitor if started previously. 1
• Continue anticoagulation as outlined above for medically managed patients. 1, 3

Long-Term Pharmacotherapy

Beta-blockers: Initiate in all patients recovering from NSTEMI unless contraindicated (e.g., decompensated heart failure, bradycardia, hypotension); continue indefinitely. 2, 4

ACE inhibitors: Initiate and continue indefinitely for patients with heart failure, left ventricular dysfunction (LVEF <0.40), hypertension, or diabetes. 2, 4

Angiotensin receptor blockers (ARBs): Use for ACE inhibitor-intolerant patients with heart failure and LVEF <0.40. 4

Statins: High-intensity statin therapy should be initiated in all NSTEMI patients for secondary prevention (though not explicitly detailed in provided evidence, this is standard of care). 1

Extended DAPT beyond 12 months: May be considered after careful assessment of ischemic versus bleeding risk, particularly in patients with very high ischemic risk and acceptable bleeding risk. 1

Critical Pitfalls to Avoid

• Do not discontinue DAPT prematurely (before 12 months) even if symptoms resolve, as this significantly increases risk of recurrent thrombotic events. 4
• Avoid concomitant use of clopidogrel with omeprazole or esomeprazole, as these significantly reduce clopidogrel's antiplatelet activity through CYP2C19 inhibition. 5
• Do not discharge patients early based solely on symptom resolution; continuous monitoring for at least 24 hours is required even in low-risk patients. 4
• In patients therapeutically anticoagulated with warfarin at presentation, do not initiate additional anticoagulant therapy until INR <2.0, but antiplatelet therapy should be started even if therapeutically anticoagulated. 1