What are the indications for prasugrel (Prasugrel) versus clopidogrel (Clopidogrel) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI)?

Indications for Prasugrel vs Clopidogrel in ACS Patients Undergoing PCI

Prasugrel should be used over clopidogrel in ACS patients undergoing PCI who are at high risk for thrombotic events, have no contraindications, and are not at high bleeding risk. 1, 2

Patient Selection Criteria

Prasugrel Indications

• Preferred for:
  • Patients with ACS (UA/NSTEMI or STEMI) undergoing PCI 1, 2
  • Patients with diabetes mellitus (shows greater benefit) 1
  • Patients with STEMI (particularly within 12 hours of symptom onset) 1
  • Patients at high risk for stent thrombosis 1

Clopidogrel Indications

• Preferred for:
  • Patients ≥75 years of age (due to increased bleeding risk with prasugrel) 2
  • Patients with body weight <60 kg (unless prasugrel dose reduced to 5 mg) 2
  • Patients with history of stroke or TIA (prasugrel contraindicated) 1, 2
  • Patients at high bleeding risk 1
  • Patients with stable coronary artery disease (non-ACS) 3
  • Patients likely to need urgent CABG 2

Dosing Considerations

Prasugrel

• Loading dose: 60 mg orally
• Maintenance dose: 10 mg daily
• Consider 5 mg daily for patients <60 kg (though efficacy not prospectively studied) 2
• Do not administer until coronary anatomy is defined in UA/NSTEMI patients 1, 2

Clopidogrel

• Loading dose: 300-600 mg orally
• Maintenance dose: 75 mg daily
• Can be administered upstream before angiography in UA/NSTEMI 1

Clinical Evidence and Efficacy

The TRITON-TIMI 38 trial demonstrated that prasugrel significantly reduced:

• Primary composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke (9.9% vs 12.1%, HR 0.81, p<0.001) 1
• Stent thrombosis (1.1% vs 2.4%, p<0.001) 1
• Nonfatal MI (7.3% vs 9.5%, p<0.001) 1

However, prasugrel showed:

• No significant reduction in cardiovascular death (2.1% vs 2.4%, p=0.31) 1
• No reduction in nonfatal stroke (1.0% vs 1.0%, p=0.93) 1

Bleeding Risk Considerations

Prasugrel is associated with increased bleeding risk:

• TIMI major hemorrhage: 2.4% vs 1.8% with clopidogrel (HR 1.32, p=0.03) 1
• Fatal bleeding: 0.4% vs 0.1% with clopidogrel (p=0.002) 1

High Bleeding Risk Factors

• Age ≥75 years
• Body weight <60 kg
• History of stroke or TIA
• Concomitant use of anticoagulants, steroids, or NSAIDs
• History of bleeding or peptic ulcer disease 1, 2

Timing Considerations

• For STEMI patients within 12 hours of symptom onset: prasugrel can be given at time of diagnosis 2
• For UA/NSTEMI patients: prasugrel should be given only after coronary anatomy is defined 1, 2
• Discontinue prasugrel at least 7 days before planned CABG 2
• Discontinue clopidogrel at least 5 days before planned CABG 1

Algorithm for P2Y12 Inhibitor Selection in ACS Patients Undergoing PCI

1. Assess patient for absolute contraindications to prasugrel:

   • History of stroke or TIA → Use clopidogrel
   • Active pathological bleeding → Use neither until resolved

2. Assess bleeding risk:

   • Age ≥75 years → Prefer clopidogrel
   • Weight <60 kg → Consider clopidogrel or reduced-dose prasugrel (5 mg)
   • History of bleeding → Prefer clopidogrel
   • Concomitant anticoagulation → Prefer clopidogrel

3. Assess thrombotic risk:

   • Diabetes mellitus → Favor prasugrel if no high bleeding risk
   • STEMI presentation → Favor prasugrel if no high bleeding risk
   • Prior stent thrombosis → Favor prasugrel if no high bleeding risk

4. Consider timing:

   • Need for urgent CABG possible → Use clopidogrel
   • UA/NSTEMI before angiography → Use clopidogrel
   • STEMI within 12 hours → Consider prasugrel if no contraindications

Common Pitfalls to Avoid

1. Using prasugrel in patients with history of stroke or TIA (absolute contraindication)
2. Administering prasugrel before coronary anatomy is defined in UA/NSTEMI patients
3. Not reducing prasugrel dose in patients <60 kg
4. Using prasugrel in patients ≥75 years without considering the increased bleeding risk
5. Not discontinuing prasugrel at least 7 days before planned CABG
6. Overlooking the need for aspirin co-administration (75-325 mg daily) with both agents

By following these guidelines and carefully assessing individual patient characteristics, clinicians can optimize the selection between prasugrel and clopidogrel to maximize reduction in thrombotic events while minimizing bleeding risk in ACS patients undergoing PCI.