NSTEMI Management and Antiplatelet Loading Doses
For NSTEMI, immediately give aspirin 162-325 mg (non-enteric coated, chewed) followed by 75-100 mg daily, plus a P2Y12 inhibitor loading dose: ticagrelor 180 mg (preferred), clopidogrel 300-600 mg, or prasugrel 60 mg if undergoing PCI. 1
Initial Antiplatelet Therapy
Aspirin
- Loading dose: 162-325 mg orally, non-enteric coated, chewed for faster absorption 2, 1
- Maintenance: 75-100 mg daily (NOT 81-325 mg as older guidelines suggested) 1
- Continue indefinitely unless contraindicated 2
- If aspirin-allergic: give clopidogrel loading dose followed by maintenance 2
P2Y12 Inhibitor Selection (Dual Antiplatelet Therapy)
Ticagrelor is preferred over clopidogrel for both invasive and ischemia-guided strategies 2, 3, 2:
- Loading: 180 mg orally
- Maintenance: 90 mg twice daily
- Critical: When using ticagrelor, aspirin dose MUST be ≤100 mg daily 2, 1
Clopidogrel (when ticagrelor unavailable/contraindicated):
Prasugrel (only at time of PCI, NOT before):
- Loading: 60 mg orally 2, 3, 5
- Maintenance: 10 mg daily (5 mg if <60 kg or ≥75 years) 4, 5
- Contraindicated: Prior stroke/TIA 2, 4, 5
- Only for patients undergoing PCI with known anatomy 2, 3
Management Strategy Algorithm
Early Invasive Strategy (PCI planned within 24 hours)
- On presentation: Aspirin 162-325 mg + ticagrelor 180 mg OR clopidogrel 300-600 mg 2, 1
- At PCI: Continue same P2Y12 inhibitor OR switch to prasugrel 60 mg if not pretreated 2, 3
- GP IIb/IIIa inhibitors: Consider only in high-risk features (elevated troponin) - eptifibatide or tirofiban preferred over abciximab 2
Ischemia-Guided (Conservative) Strategy
- On admission: Aspirin + clopidogrel OR ticagrelor (ticagrelor preferred) 2, 6, 4
- Continue for up to 12 months 2, 6, 4
- If recurrent ischemia develops: proceed to angiography 6, 4
Anticoagulation (Required for All Patients)
Choose ONE of the following 2, 3:
Enoxaparin (preferred):
- 1 mg/kg subcutaneous every 12 hours
- Reduce to 1 mg/kg once daily if CrCl <30 mL/min
- Optional 30 mg IV loading dose
- Continue until PCI or hospital discharge (up to 8 days) 2, 3
Fondaparinux:
- 2.5 mg subcutaneous daily
- Continue until PCI or discharge
- Must give additional UFH bolus at time of PCI 2, 3
Bivalirudin:
- 0.10 mg/kg loading + 0.25 mg/kg/hour infusion
- Only for early invasive strategy
- Continue until angiography/PCI 2, 3
UFH:
- 60 IU/kg bolus (max 4000 IU) + 12 IU/kg/hour infusion (max 1000 IU/hour)
- Adjust to therapeutic aPTT
- Continue 48 hours or until PCI 2, 3
Critical Pitfalls to Avoid
DO NOT routinely pretreat with P2Y12 inhibitors if coronary anatomy unknown and early invasive strategy planned - recent evidence shows no benefit for type 4a MI but increased bleeding 7, 8
DO NOT use prasugrel before knowing coronary anatomy - only give at time of PCI 2, 3, 5
DO NOT use prasugrel in patients with prior stroke/TIA - absolute contraindication due to increased intracranial hemorrhage 2, 4, 5
DO NOT use aspirin >100 mg daily with ticagrelor - associated with worse outcomes in PLATO trial 2, 1
DO NOT use enteric-coated aspirin initially - delayed absorption 2
DO NOT use triple antiplatelet therapy routinely (aspirin + P2Y12 + GP IIb/IIIa upfront) - increases bleeding without clear benefit 6, 7
Duration of Therapy
- Aspirin: Indefinitely 2, 3, 2
- P2Y12 inhibitor: Minimum 12 months post-stenting 2, 3, 2
- May discontinue earlier if bleeding risk outweighs benefit 3
Special Considerations
If undergoing CABG:
- Continue aspirin 6, 4
- Stop clopidogrel ≥5 days before surgery 6, 4
- Stop prasugrel ≥7 days before surgery 6, 4, 5
- Stop ticagrelor ≥5 days before surgery 6, 4
Renal dysfunction: Dose-adjust enoxaparin; ticagrelor showed particular benefit in this population 9
Diabetes: Prasugrel showed greatest benefit in diabetic patients undergoing PCI 9