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

NSTEMI Treatment

For patients with NSTEMI, immediately administer aspirin 162-325 mg and initiate dual antiplatelet therapy with a P2Y12 inhibitor (preferably ticagrelor or prasugrel over clopidogrel), along with parenteral anticoagulation, followed by risk stratification to determine timing of invasive coronary angiography within 24-48 hours for high-risk patients or a conservative approach for lower-risk patients. 1, 2, 3

Immediate Initial Management

Upon presentation, the following interventions should be implemented without delay:

• Aspirin 162-325 mg should be administered immediately (or 75-250 mg IV if oral not tolerated), followed by maintenance dosing of 75-100 mg daily indefinitely 4, 1
• Admit to a monitored unit with continuous cardiac rhythm monitoring for at least 24 hours 1, 2
• Administer supplemental oxygen only if arterial oxygen saturation is <90%—routine oxygen is not indicated 1, 2
• Nitroglycerin should be considered for ongoing ischemic chest pain unless contraindicated (systolic BP <90 mmHg, severe bradycardia, right ventricular infarction, or recent phosphodiesterase inhibitor use within 24-48 hours) 2
• Beta-blockers should be initiated early to reduce myocardial oxygen demand by decreasing heart rate, blood pressure, and contractility 1, 2
• Morphine sulfate IV may be considered for uncontrolled ischemic chest discomfort despite nitroglycerin, though use cautiously as it may delay absorption of oral antiplatelet agents 1

Antiplatelet Therapy Strategy

Dual antiplatelet therapy (DAPT) is the cornerstone of pharmacologic management:

P2Y12 Inhibitor Selection (in order of preference):

1. Ticagrelor (loading dose 180 mg, then 90 mg twice daily) is preferred regardless of whether invasive or conservative strategy is planned 4, 2, 3
2. Prasugrel (loading dose 60 mg, then 10 mg daily; reduce to 5 mg daily if age ≥75 years or weight <60 kg) for patients naive to P2Y12 inhibitors who are undergoing PCI and have no history of stroke/TIA 4, 3
3. Clopidogrel (loading dose 300-600 mg, then 75 mg daily) only when ticagrelor or prasugrel are unavailable, not tolerated, or contraindicated 4, 3, 5

Critical caveat: Clopidogrel is a prodrug requiring CYP2C19 metabolism—patients who are CYP2C19 poor metabolizers (homozygous for nonfunctional alleles) form less active metabolite and have reduced antiplatelet effect. Consider genetic testing or preferentially use ticagrelor or prasugrel in these patients 5.

Timing of P2Y12 Inhibitor Administration:

• For early invasive strategy: Administer loading dose before or at the time of diagnostic angiography 4, 1
• For conservative strategy: Administer loading dose as soon as possible after admission 4, 1

Duration of DAPT:

• Continue P2Y12 inhibitor for at least 12 months after NSTEMI, regardless of whether stent was placed 4, 1
• For patients receiving drug-eluting stents (DES), continue for at least 12 months; for bare-metal stents (BMS), up to 12 months 4
• If bleeding risk outweighs benefit, earlier discontinuation may be considered 4
• Continuation beyond 12 months after DES placement may be considered 4

Anticoagulation Strategy

Parenteral anticoagulation must be administered to all NSTEMI patients in addition to antiplatelet therapy:

Anticoagulant Options (all acceptable):

• Unfractionated heparin (UFH) is recommended as routine first-line therapy 4, 1, 3
• Enoxaparin should be considered as an alternative 4, 1, 3
• Fondaparinux may be used 1, 3
• Bivalirudin may be considered 4, 3

Duration of Anticoagulation:

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

Risk Stratification and Management Strategy Selection

The decision between early invasive versus conservative strategy depends on risk assessment:

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

• Refractory angina despite medical therapy 1, 2, 3
• Hemodynamic instability or cardiogenic shock 1, 2, 3
• Electrical instability (life-threatening arrhythmias, ventricular tachycardia/fibrillation) 1, 2, 3
• Elevated cardiac biomarkers (troponin positive) 4, 1
• High GRACE or TIMI risk score 1, 2, 3
• Recurrent symptoms or ischemia during hospitalization 4, 1

Conservative Strategy (selective invasive) is appropriate for:

• Lower-risk patients without ongoing ischemia 1, 3
• Patients with extensive comorbidities (liver failure, pulmonary failure, cancer) where revascularization risks outweigh benefits 4
• Patients who will not consent to revascularization 4
• Low likelihood of acute coronary syndrome 4

Important note: The decision may incorporate physician and patient preference when risk is intermediate 4.

Post-Angiography Management

If PCI is Performed:

• Continue aspirin indefinitely 4, 1, 3
• Administer P2Y12 inhibitor loading dose if not given before angiography 4, 1, 3
• After PCI, use aspirin 81 mg daily in preference to higher maintenance doses 4
• GP IIb/IIIa inhibitors (eptifibatide or tirofiban) should be considered for bail-out if there is evidence of no-reflow or thrombotic complication 4

If CABG is Planned:

• Continue aspirin indefinitely 1, 3
• Discontinue clopidogrel 5-7 days before elective CABG 4, 1, 3
• Discontinue prasugrel at least 7 days before surgery 4, 3
• Discontinue ticagrelor at least 3-5 days before surgery 4, 3

If Medical Management is Selected:

• Continue aspirin indefinitely 1, 3
• Administer P2Y12 inhibitor loading dose if not given before angiography and continue for up to 12 months 4, 1

Long-Term Secondary Prevention

Cardiac Function Assessment:

• Measure left ventricular ejection fraction (LVEF) in all patients 1, 2, 3
• If LVEF ≤0.40, consider diagnostic angiography if not already performed 1, 3
• If LVEF >0.40, consider stress testing for risk stratification 1, 3

Pharmacologic Secondary Prevention:

• ACE inhibitors should be initiated for patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes 1, 2, 3
• ARBs should be considered for patients intolerant to ACE inhibitors 1, 2, 3
• Beta-blockers should be continued long-term for all NSTEMI patients without contraindications 3
• High-intensity statin therapy should be initiated regardless of baseline LDL levels 1

Anticoagulation Considerations:

• For patients requiring long-term oral anticoagulation (atrial fibrillation, LV thrombus, mechanical valve), addition of warfarin may be reasonable with target INR 2.0-3.0 (preferably 2.0-2.5 when combined with DAPT, especially in elderly) 4
• Triple therapy (aspirin + P2Y12 inhibitor + warfarin) significantly increases bleeding risk—monitor closely for bleeding, especially gastrointestinal 4

Critical Pitfalls to Avoid

• Never use NSAIDs (except aspirin) during hospitalization—they increase risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture 1, 2
• Avoid immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade 1, 2
• Do not administer IV ACE inhibitors within the first 24 hours due to increased hypotension risk 1
• Avoid concomitant use of clopidogrel with omeprazole or esomeprazole—these significantly reduce clopidogrel's antiplatelet activity via CYP2C19 inhibition 5
• For patients with history of gastrointestinal bleeding on DAPT, prescribe proton pump inhibitors (PPIs) concomitantly, but avoid omeprazole/esomeprazole if using clopidogrel 4, 5
• Avoid strong CYP2C19 inducers with clopidogrel as they may potentiate bleeding risk 5
• Do not perform early invasive strategy in patients with acute chest pain and low likelihood of ACS 4