Why is prasugrel (Prasugrel) preferred over Brilinta (Ticagrelor) for patients undergoing percutaneous coronary intervention (PCI)?

Prasugrel vs. Ticagrelor in PCI: Clinical Decision Making

Prasugrel is preferred over ticagrelor (Brilinta) in patients undergoing PCI who are not at high risk for bleeding complications due to its superior efficacy in reducing stent thrombosis and major adverse cardiovascular events. 1

Comparative Efficacy and Guidelines

The 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for management of acute coronary syndromes provides clear recommendations regarding P2Y12 inhibitor selection:

• Both prasugrel and ticagrelor are recommended over clopidogrel for patients with ACS undergoing PCI 1
• Prasugrel is specifically recommended for patients who are not at high risk for bleeding complications 1
• In patients with NSTE-ACS undergoing PCI, prasugrel or ticagrelor is recommended to reduce MACE and stent thrombosis 1

Key Advantages of Prasugrel

Efficacy Benefits

• Prasugrel demonstrated a 19% relative reduction in the primary efficacy endpoint (cardiovascular death, nonfatal MI, or stroke) compared to clopidogrel 2
• Significantly reduced rates of stent thrombosis (1.1% vs 2.4%) compared to clopidogrel 1, 2
• Particularly beneficial in patients with diabetes, showing a 30% relative risk reduction in MACE compared to 14% in non-diabetics 1

Pharmacological Advantages

• Less susceptibility to genetic variations (CYP2C19 polymorphisms) that affect drug metabolism 2
• More consistent antiplatelet effect compared to clopidogrel 2

Real-World Comparative Data

Recent observational studies comparing prasugrel and ticagrelor have shown:

• In propensity-matched analyses, prasugrel was associated with 22% lower net adverse clinical events compared to ticagrelor 3
• Lower rates of major adverse cardiovascular events and major bleeding with prasugrel compared to ticagrelor in some real-world settings 3, 4

Important Contraindications and Precautions

Prasugrel should NOT be used in patients with:

• History of stroke or transient ischemic attack 1
• Active pathological bleeding 1
• Patients likely to undergo urgent CABG 1

Special considerations:

• Use with caution in patients ≥75 years of age (generally not recommended except in high-risk situations like diabetes or prior MI) 1
• Consider dose reduction to 5 mg daily in patients weighing <60 kg 1
• Discontinue at least 7 days before planned surgery (vs. 5 days for clopidogrel and 3-5 days for ticagrelor) 1

Bleeding Risk Management

• Prasugrel is associated with increased bleeding risk compared to clopidogrel (32% increased relative risk of major bleeding) 1, 2
• Despite the increased bleeding risk, the net clinical benefit (including mortality, ischemic events, and bleeding) favors prasugrel in appropriate patients 1
• Consider proton pump inhibitors in patients at risk for gastrointestinal bleeding 1

Algorithm for P2Y12 Inhibitor Selection in PCI

1. First-line for most ACS patients undergoing PCI:

   • Prasugrel or ticagrelor (both superior to clopidogrel)

2. Choose prasugrel when:

   • Patient has diabetes (greater benefit)
   • High concern for stent thrombosis
   • No history of stroke/TIA
   • Age <75 years (unless high-risk features present)
   • Weight ≥60 kg
   • No planned surgery within 7 days

3. Choose ticagrelor when:

   • History of stroke/TIA (contraindication to prasugrel)
   • Upstream treatment needed before knowing coronary anatomy
   • Medically managed ACS without PCI planned
   • Patient unable to take twice-daily medication

4. Choose clopidogrel when:

   • Prasugrel and ticagrelor are contraindicated or unavailable
   • High bleeding risk patients
   • Fibrinolytic therapy was administered for STEMI

By following this evidence-based approach to P2Y12 inhibitor selection, clinicians can optimize outcomes for patients undergoing PCI, balancing the reduction in ischemic events with bleeding risk.