What is the recommended initial management for a patient with non‑ST‑segment elevation myocardial infarction, including loading doses of aspirin and a P2Y12 inhibitor and a heparin infusion?

NSTEMI Management: Dual Antiplatelet Therapy and Heparin Infusion

Immediate Antiplatelet Loading

Administer aspirin 162–325 mg (non-enteric coated, chewable) immediately upon presentation, followed by a P2Y12 inhibitor loading dose, and initiate parenteral anticoagulation with unfractionated heparin or enoxaparin concurrently. 1, 2, 3

• Aspirin: Give 162–325 mg loading dose immediately, then 75–100 mg daily indefinitely 1, 2
• P2Y12 inhibitor selection depends on your invasive strategy timing and patient characteristics 1:
  • Ticagrelor 180 mg loading (then 90 mg twice daily) is preferred for all NSTEMI patients regardless of invasive vs. conservative strategy 1, 3
  • Prasugrel 60 mg loading (then 10 mg daily; 5 mg if age ≥75 years or weight <60 kg) should be considered in preference to ticagrelor specifically for patients proceeding to PCI, but only after coronary anatomy is defined 1, 3
  • Clopidogrel 600 mg loading (then 75 mg daily) is reserved only when prasugrel or ticagrelor are unavailable, contraindicated, or not tolerated 1, 2

Critical Contraindication

Do not use prasugrel in patients with prior stroke or TIA—it causes harm in this population. 1

Parenteral Anticoagulation Strategy

All NSTEMI patients require immediate parenteral anticoagulation in addition to dual antiplatelet therapy, regardless of whether an invasive or conservative strategy is planned. 1, 3, 4

Agent Selection Algorithm

Choose your anticoagulant based on renal function, bleeding risk, and planned invasive strategy timing:

For Normal to Mild Renal Impairment (CrCl >30 mL/min):

• Unfractionated heparin (UFH): 60 U/kg bolus (max 4,000 U), then 12 U/kg/h infusion (max 1,000 U/h); target aPTT 1.5–2.0 × control (50–70 seconds) 3
• Enoxaparin: 1 mg/kg subcutaneously every 12 hours 1, 3
• Fondaparinux: 2.5 mg subcutaneously daily (lowest bleeding risk, preferred for conservative strategy) 3

For Severe Renal Impairment (CrCl <30 mL/min):

• UFH is mandatory—it does not accumulate with renal dysfunction and can be monitored with aPTT 3
• Avoid enoxaparin and fondaparinux due to unpredictable pharmacokinetics 3

Duration of Anticoagulation

The duration depends on your management strategy:

• UFH: Continue for at least 48 hours or until PCI, whichever comes first 1, 3
• Enoxaparin or fondaparinux: Continue for duration of hospitalization, up to 8 days 1, 3
• After uncomplicated PCI: Discontinue anticoagulation immediately 3

Critical Pitfall: Fondaparinux During PCI

Never use fondaparinux as the sole anticoagulant during PCI—you must add UFH bolus to prevent catheter thrombosis. 3

Timing of Invasive Strategy

Your decision on when to perform angiography dictates the entire management approach:

Immediate Invasive (<2 hours):

Indicated for 1, 3:

• Refractory or recurrent angina despite optimal medical therapy
• Hemodynamic instability or cardiogenic shock
• Life-threatening arrhythmias or cardiac arrest

Early Invasive (<24 hours):

Indicated for 1, 3:

• Elevated cardiac troponin with high-risk features
• Dynamic ST-segment or T-wave changes
• High GRACE or TIMI risk score
• Diabetes mellitus

Conservative Strategy:

Appropriate for 1, 3:

• Low GRACE score without ongoing ischemia
• Significant comorbidities where procedural risk exceeds benefit

Pre-Treatment Controversy

The 2021 ESC guidelines explicitly recommend against routine pre-treatment with P2Y12 inhibitors when coronary anatomy is unknown and early invasive management is planned. 1 This represents a shift from older ACC/AHA guidance that allowed earlier loading. The rationale is to avoid unnecessary bleeding if CABG is required and to allow prasugrel use (which requires knowing anatomy first). However, ticagrelor may still be given early since it can be used regardless of anatomy 1.

Anticoagulation During PCI

Adjust your anticoagulation based on timing of last dose:

If Using UFH:

• Continue through PCI with additional boluses to maintain ACT 250–300 seconds (HemoTec) or 300–350 seconds (Hemochron) 3
• If GP IIb/IIIa inhibitors are used, target ACT ≈200 seconds 3

If Using Enoxaparin:

• Last dose ≤8 hours before PCI: No additional dose needed 3
• Last dose 8–12 hours before PCI: Give 0.3 mg/kg IV bolus 3

Glycoprotein IIb/IIIa Inhibitors

Do not use GP IIb/IIIa inhibitors routinely or upstream—reserve them for bail-out situations only (no-reflow or thrombotic complications during PCI). 1 The 2021 ESC guidelines downgraded their use due to increased bleeding risk without reduction in ischemic events when combined with modern P2Y12 inhibitors 3.

Duration of Dual Antiplatelet Therapy

Continue dual antiplatelet therapy for at least 12 months after NSTEMI, regardless of whether a stent was placed. 1, 5 This recommendation is Class I, Level B evidence and applies to all three P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) 1.

The only exception: If bleeding risk clearly outweighs benefit, earlier discontinuation may be considered 1.

Pre-CABG Management

If CABG is required, adjust anticoagulation and antiplatelet therapy:

• Continue aspirin through CABG 3
• Stop ticagrelor 5 days before elective CABG 3
• Stop prasugrel at least 7 days before CABG 3
• Stop clopidogrel 5–7 days before elective CABG 1, 3
• Continue UFH through CABG 3
• Stop enoxaparin 12–24 hours before CABG and switch to UFH 3

Common Pitfall: Switching Anticoagulants

Never switch between different anticoagulants—this significantly increases bleeding risk. 3 Choose one agent at presentation and continue it through your planned strategy.