What is the recommended treatment for a patient presenting with Non-ST-Elevation Myocardial Infarction (NSTEMI)?

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

All patients presenting with NSTEMI should receive immediate aspirin 150-300 mg orally (or 75-250 mg IV), dual antiplatelet therapy with a P2Y12 inhibitor (preferably ticagrelor or prasugrel over clopidogrel), parenteral anticoagulation, and risk stratification to determine timing of invasive coronary angiography within 2-72 hours based on clinical risk features. 1

Immediate Initial Management (First Medical Contact)

Diagnostic Evaluation

• Obtain a 12-lead ECG within 10 minutes of first medical contact and have it interpreted immediately by an experienced physician 1
• Measure high-sensitivity cardiac troponin at 0 hours and 1 hour later using the ESC 0h/1h algorithm for rapid diagnosis 1
• If the first two troponin measurements are inconclusive and clinical presentation still suggests acute coronary syndrome, perform additional testing after 3 hours 1
• Perform echocardiography to evaluate left ventricular function and exclude differential diagnoses 1, 2

Monitoring and Supportive Care

• Admit to a monitored unit with continuous rhythm monitoring for at least 24 hours (or until PCI, whichever comes first) 1, 3
• Extend rhythm monitoring beyond 24 hours for patients at increased risk for cardiac arrhythmias 1
• Administer supplemental oxygen only if arterial oxygen saturation is <90% 3
• Consider sublingual or intravenous nitroglycerin for ongoing ischemic symptoms unless contraindicated (systolic BP <90 mmHg, severe bradycardia, right ventricular infarction, or recent phosphodiesterase inhibitor use within 24-48 hours) 3
• Initiate beta-blockers to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility 3

Antiplatelet Therapy

Aspirin

• Administer aspirin immediately at a loading dose of 150-300 mg orally (or 75-250 mg IV if oral route unavailable) 1
• Continue aspirin indefinitely at a maintenance dose of 75-100 mg daily 1, 3
• If ticagrelor is selected as the P2Y12 inhibitor, limit aspirin maintenance dose to ≤100 mg daily 1

P2Y12 Inhibitor Selection

A P2Y12 receptor inhibitor must be added to aspirin and maintained for 12 months unless there are contraindications or excessive bleeding risk. 1

The preferred options in order of preference are:

• Ticagrelor (first-line choice): Loading dose 180 mg, then 90 mg twice daily, recommended regardless of planned treatment strategy (invasive or conservative) 1, 4

• Prasugrel (alternative for invasive strategy): Loading dose 60 mg, maintenance 10 mg daily (reduce to 5 mg daily for patients ≥75 years or body weight <60 kg); use only in P2Y12 inhibitor-naïve patients proceeding to PCI 1

  • Contraindicated in patients with history of stroke or transient ischemic attack 1, 5

• Clopidogrel (third-line option): Loading dose 300-600 mg, maintenance 75 mg daily; use only when ticagrelor or prasugrel are unavailable, not tolerated, or contraindicated 1, 6

  • Important caveat: Approximately 2% of White patients, 4% of Black patients, and 14% of Asian patients are CYP2C19 poor metabolizers who form less active metabolite and have reduced antiplatelet effect 6
  • Consider genetic testing for CYP2C19 status if clopidogrel is used; if poor metabolizer identified, switch to ticagrelor or prasugrel 6

Glycoprotein IIb/IIIa Inhibitors

• Do not routinely administer GP IIb/IIIa antagonists before coronary anatomy is known 1
• Do not use routine pre-treatment with P2Y12 inhibitors in patients with unknown coronary anatomy when early invasive management is planned 1

Anticoagulant Therapy

Parenteral anticoagulation is mandatory for all NSTEMI patients in addition to antiplatelet therapy, initiated at the time of diagnosis. 1, 3

Options include:

• Unfractionated heparin (UFH): Continue for at least 48 hours or until discharge if given before diagnostic angiography 3, 4
• Enoxaparin: Continue for duration of hospitalization, up to 8 days 4
• Fondaparinux: Continue for duration of hospitalization, up to 8 days 4
• Bivalirudin: Particularly if GP IIb/IIIa inhibitors are not planned 2

For patients requiring long-term anticoagulation (e.g., atrial fibrillation), use triple antithrombotic therapy (oral anticoagulant + aspirin + clopidogrel) for up to 1 month (typically 1 week or until hospital discharge), followed by dual therapy (oral anticoagulant + clopidogrel) for up to 1 year, then oral anticoagulant monotherapy thereafter 7

Risk Stratification and Timing of Invasive Strategy

Immediate Invasive Strategy (<2 hours)

Proceed to catheterization laboratory within 2 hours if any of the following very-high-risk criteria are present: 1

• Hemodynamic instability or cardiogenic shock
• Recurrent or ongoing chest pain refractory to medical treatment
• Life-threatening arrhythmias or cardiac arrest
• Mechanical complications of MI
• Acute heart failure with refractory angina or ST-segment deviation
• Recurrent dynamic ST- or T-wave changes, particularly with intermittent ST-elevation

Early Invasive Strategy (<24 hours)

Perform coronary angiography within 24 hours if any of the following high-risk criteria are present: 1

• Rise or fall in cardiac troponin compatible with MI
• Dynamic ST- or T-wave changes (symptomatic or silent)
• GRACE score >140

Invasive Strategy (<72 hours)

Perform coronary angiography within 72 hours if any of the following intermediate-risk criteria are present: 1

• Diabetes mellitus
• Renal insufficiency (eGFR <60 mL/min/1.73 m²)
• LVEF <40% or congestive heart failure
• Early post-infarction angina
• Recent PCI or prior CABG
• GRACE risk score 109-140
• Recurrent symptoms or known ischemia on non-invasive testing

Conservative Strategy

A conservative (non-invasive) strategy is appropriate only for low-risk patients without ongoing ischemia or those with significant comorbidities where invasive risks outweigh benefits 4

Post-Angiography Management

If PCI is Performed

• Continue aspirin indefinitely 4
• Administer P2Y12 inhibitor loading dose if not given before angiography 4
• Continue P2Y12 inhibitor for at least 12 months 4

If CABG is Planned

• Continue aspirin 4
• Stop clopidogrel 5-7 days before elective CABG 4
• Stop prasugrel at least 7 days before surgery 2
• Stop ticagrelor at least 5 days before surgery 2

If Medical Management is Selected

• Continue aspirin indefinitely 4
• Administer P2Y12 inhibitor loading dose if not given before angiography 4
• Continue P2Y12 inhibitor for at least 12 months 1

Long-Term Secondary Prevention

Cardiac Function Assessment

• Measure left ventricular ejection fraction in all patients 4
• If LVEF ≤40%, consider diagnostic angiography if not already performed 4
• If LVEF >40%, consider stress testing for risk stratification 4

Pharmacotherapy

• ACE inhibitors: Initiate for all patients with heart failure, LV dysfunction (LVEF <40%), hypertension, or diabetes 3, 4
• ARBs: Use as alternative for ACE inhibitor-intolerant patients 3, 4
• Beta-blockers: Continue indefinitely for all NSTEMI patients without contraindications 2
• High-intensity statin therapy: Initiate regardless of baseline LDL cholesterol levels 4

Critical Contraindications and Pitfalls

Medications to Avoid

• NSAIDs (except aspirin): Avoid during hospitalization due to increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture 3, 4
• Immediate-release dihydropyridine calcium channel blockers: Do not administer without adequate beta-blockade 3
• Intravenous ACE inhibitors: Avoid within first 24 hours due to increased hypotension risk 4
• Omeprazole or esomeprazole with clopidogrel: Avoid concomitant use as these significantly reduce clopidogrel's antiplatelet activity 6

Drug Interactions

• Avoid strong CYP2C19 inducers with clopidogrel as they may potentiate bleeding risk 6
• Consider alternative P2Y12 inhibitors (ticagrelor or prasugrel) in patients requiring proton pump inhibitors 6

Timing Considerations

• The median time from P2Y12 inhibitor loading to angiography in contemporary practice is approximately 17 hours, which appears safe with very low bleeding rates (0.24% major bleeding) 8
• Upstream loading (≥4 hours before angiography) with P2Y12 inhibitors is associated with low rates of in-hospital major adverse cardiovascular events (0.7%) and stent thrombosis (0.18%) 8