What is the recommended management approach for Acute Coronary Syndrome (ACS) with Non-ST-Elevation Myocardial Infarction (NSTEMI) according to the latest American Heart Association (AHA) guidelines?

Management of NSTEMI According to 2025 AHA Guidelines

For patients with NSTEMI, dual antiplatelet therapy with aspirin plus ticagrelor or prasugrel (preferred over clopidogrel) is recommended for at least 12 months, combined with an early invasive strategy using radial artery access and intracoronary imaging for complex lesions. 1

Immediate Antiplatelet Therapy

Loading Doses (Pre-PCI or at Time of PCI)

• Aspirin: 81-325 mg non-enteric-coated orally 1
• P2Y12 inhibitor - choose one of the following 1:
  • Ticagrelor: 180 mg loading dose (preferred) 1
  • Prasugrel: 60 mg loading dose (preferred over clopidogrel) 1, 2
  • Clopidogrel: 600 mg loading dose (if ticagrelor/prasugrel contraindicated) 1, 3

Critical Contraindications to Note

• Prasugrel is absolutely contraindicated in patients with prior stroke or TIA 1, 2
• Prasugrel is generally not recommended in patients ≥75 years or <60 kg due to increased bleeding risk, except in high-risk situations (diabetes or prior MI) 2
• Ticagrelor does NOT have the stroke/TIA contraindication that prasugrel has 4

Initial Anticoagulation (Choose One)

All patients require anticoagulation in addition to dual antiplatelet therapy 1:

• Enoxaparin: 1 mg/kg subcutaneous every 12 hours (reduce to once daily if CrCl <30 mL/min) 1
• Bivalirudin: 0.10 mg/kg loading dose, then 0.25 mg/kg/hour (for early invasive strategy only) 1
• Fondaparinux: 2.5 mg subcutaneous daily 1
  • Critical caveat: Must add UFH or bivalirudin at time of PCI due to catheter thrombosis risk 1
• Unfractionated heparin: 60 IU/kg bolus (max 4000 IU), then 12 IU/kg/hour (max 1000 IU/h) adjusted to aPTT 1

Invasive Strategy Timing

Urgent/Immediate (<2 hours) 1

Indicated for patients with:

• Refractory angina despite medical therapy 1
• Hemodynamic instability 1
• Electrical instability (sustained VT/VF) 1
• Signs of heart failure or new mitral regurgitation 1

Early Invasive (Within 24 hours) 1

Indicated for initially stabilized high-risk patients with:

• GRACE risk score >140 1
• Elevated troponin with dynamic changes 1
• New ST-segment depression 1

Delayed Invasive (24-72 hours) 1

Reasonable for patients not at high/intermediate risk 1

PCI Procedural Recommendations

The 2025 guidelines emphasize two key procedural strategies 1:

1. Radial artery approach preferred over femoral to reduce bleeding, vascular complications, and death 1
2. Intracoronary imaging recommended to guide PCI in complex coronary lesions 1

Complete Revascularization Strategy

• Complete revascularization is recommended for NSTEMI patients 1
• Choice between multivessel PCI versus CABG depends on coronary disease complexity and comorbidities 1
• Do NOT perform routine PCI of non-infarct arteries in patients with cardiogenic shock 1

Maintenance Antiplatelet Therapy (Post-PCI)

Duration: At Least 12 Months 1

Aspirin (indefinitely) 1:

• 81 mg daily preferred (especially with ticagrelor - mandatory dose) 1
• 81-325 mg daily acceptable with clopidogrel or prasugrel 1

P2Y12 Inhibitor (choose one) 1:

• Ticagrelor: 90 mg twice daily (preferred) 1
• Prasugrel: 10 mg daily (5 mg if <60 kg) 1, 2
• Clopidogrel: 75 mg daily 1, 3

Ticagrelor Monotherapy Strategy (New in 2025)

In patients who have tolerated dual antiplatelet therapy with ticagrelor, transition to ticagrelor monotherapy is recommended ≥1 month after PCI to reduce bleeding risk 1

Special Situations

Patients Requiring Long-Term Anticoagulation (e.g., Atrial Fibrillation)

Triple therapy duration should be minimized 1:

• 1-4 weeks: Anticoagulant + aspirin + P2Y12 inhibitor (preferably clopidogrel) 1
• Then discontinue aspirin and continue anticoagulant + clopidogrel up to 12 months 1
• After 12 months: Anticoagulant monotherapy 1

Important: Apixaban is NOT standard therapy for NSTEMI unless there is a specific indication like atrial fibrillation 3

Bleeding Risk Reduction Strategies 1

Three evidence-based approaches:

1. Proton pump inhibitor for patients at risk of GI bleeding 1
2. Transition to ticagrelor monotherapy ≥1 month post-PCI 1
3. Aspirin discontinuation at 1-4 weeks in patients requiring anticoagulation 1

GP IIb/IIIa Inhibitors

• May be reasonable at time of PCI in high-risk patients (elevated troponin) not adequately pretreated with clopidogrel or ticagrelor 1
• Options: abciximab, double-bolus eptifibatide, or high-dose bolus tirofiban 1

Cardiogenic Shock Management

For selected patients with cardiogenic shock from acute MI, microaxial flow pump use is reasonable to reduce death, but complications (bleeding, limb ischemia, renal failure) are higher 1

• Emergency revascularization of culprit vessel is indicated 1
• Careful attention to vascular access and weaning is critical 1

Common Pitfalls to Avoid

1. Never give prasugrel to patients with prior stroke/TIA - this is an absolute contraindication 1, 2
2. Never use fondaparinux alone during PCI - must add UFH or bivalirudin due to catheter thrombosis risk 1
3. Never use fibrinolytic therapy in NSTEMI - it is contraindicated 1
4. Remember aspirin dose with ticagrelor must be 81 mg daily (higher doses decrease effectiveness) 1, 4
5. Discontinue anticoagulation after PCI unless compelling reason to continue 1