In a patient with a prior ischemic cerebrovascular accident (stroke) more than three months ago and no active bleeding, can we give the standard antiplatelet loading doses for non‑ST‑segment elevation myocardial infarction (NSTEMI)?

Antiplatelet Loading Doses in NSTEMI with Prior Stroke History

In patients with NSTEMI and a history of ischemic stroke more than 3 months ago, you can safely administer standard loading doses of aspirin and clopidogrel or ticagrelor, but prasugrel is absolutely contraindicated due to prior stroke. 1

Recommended Antiplatelet Loading Strategy

Aspirin Loading

• Administer aspirin 150-300 mg oral loading dose (or 75-250 mg IV) immediately, regardless of prior stroke history 1
• The presence of remote ischemic stroke (>3 months ago) is not a contraindication to aspirin loading 1
• Continue with maintenance dose of 75-100 mg daily long-term 1

P2Y12 Inhibitor Selection - Critical Distinction

Safe Options:

• Ticagrelor 180 mg loading dose is recommended and safe in patients with prior stroke 1

  • Maintenance: 90 mg twice daily for 12 months 1
  • This is the preferred potent P2Y12 inhibitor in this population 1

• Clopidogrel 600 mg loading dose is safe in patients with prior stroke 1

  • Maintenance: 75 mg daily for 12 months 1
  • Use when ticagrelor is contraindicated, not available, or not tolerated 1

Absolutely Contraindicated:

• Prasugrel is Class III: Harm (contraindicated) in patients with any prior history of stroke or TIA 1
• This is a firm contraindication regardless of how remote the stroke was 1
• The TRITON-TIMI 38 trial showed net harm with increased fatal and intracranial bleeding in stroke patients 1

Clinical Algorithm for P2Y12 Selection

Step 1: Confirm stroke history details

• If any prior stroke or TIA → Prasugrel is absolutely excluded 1

Step 2: Choose between ticagrelor and clopidogrel

• First choice: Ticagrelor 180 mg loading (unless contraindications exist) 1
• Second choice: Clopidogrel 600 mg loading (if ticagrelor unavailable or not tolerated) 1

Step 3: Administer loading doses

• Give aspirin and chosen P2Y12 inhibitor as early as possible before or at time of PCI 1
• Do not delay for coronary anatomy definition when using ticagrelor or clopidogrel 1

Critical Pitfalls to Avoid

The Prasugrel Trap

• Never assume "old stroke" makes prasugrel acceptable - the contraindication is absolute and permanent 1
• Even strokes occurring years prior remain a contraindication 1
• The increased risk of fatal intracranial hemorrhage persists regardless of stroke timing 1

Additional High-Risk Features with Prasugrel

• Age ≥75 years: generally not recommended due to increased bleeding risk 1
• Body weight <60 kg: increased exposure to active metabolite and bleeding risk 1
• These factors compound the stroke contraindication 1

Anticoagulation Considerations

Parenteral Anticoagulation During PCI

• Unfractionated heparin (UFH) 70-100 IU/kg IV bolus is recommended during PCI 1
• Reduce to 50-70 IU/kg if GP IIb/IIIa inhibitor is used 1
• Enoxaparin 0.5 mg/kg IV bolus is an alternative if patient pre-treated with subcutaneous enoxaparin 1

Duration of Therapy

• Continue dual antiplatelet therapy (aspirin + P2Y12 inhibitor) for at least 12 months 1
• Discontinue parenteral anticoagulation immediately after PCI unless compelling indication exists 1

Evidence Quality Note

The contraindication for prasugrel in stroke patients comes from the highest quality evidence: the TRITON-TIMI 38 trial showed definitive harm with increased fatal bleeding 1. The 2020 ESC and 2014 AHA/ACC guidelines both give this a Class III (Harm) recommendation with Level B evidence 1. This represents one of the clearest contraindications in cardiovascular medicine.