Why is prasugrel (Prasugrel) given for Percutaneous Coronary Intervention (PCI)?

Prasugrel in Percutaneous Coronary Intervention (PCI)

Prasugrel is given during PCI because it significantly reduces the risk of thrombotic events, including stent thrombosis, myocardial infarction, and cardiovascular death compared to clopidogrel, though with an increased bleeding risk. 1

Mechanism and Benefits

Prasugrel is a P2Y12 receptor inhibitor that provides:

• More potent and consistent platelet inhibition than clopidogrel 2
• Faster onset of action 1
• Less susceptibility to genetic variations (CYP2C19 polymorphisms) that affect drug metabolism 1

In the pivotal TRITON-TIMI 38 trial, prasugrel demonstrated:

• 19% relative reduction in the primary efficacy endpoint (cardiovascular death, nonfatal MI, or stroke) compared to clopidogrel 1
• 2.2% absolute risk reduction (NNT = 46) 1
• Significant reduction in nonfatal MI rates (7.3% vs 9.5%) 1
• Dramatic reduction in stent thrombosis (1.1% vs 2.4%) 1

Dosing Protocol

• Loading dose: 60 mg administered before, during, or within 1 hour after PCI (but only after coronary anatomy has been defined in UA/NSTEMI) 1
• Maintenance dose: 10 mg daily for at least 12 months and up to 15 months 1
• Consider 5 mg daily maintenance dose for patients weighing <60 kg 3

Safety Considerations and Contraindications

Prasugrel is associated with increased bleeding risk:

• 32% increased relative risk of major bleeding compared to clopidogrel 1
• Higher rates of life-threatening and fatal bleeding 1

Absolute contraindications 1, 3:

• Active pathological bleeding
• History of TIA or stroke
• Likely urgent CABG

Use with caution or avoid in:

• Patients ≥75 years (generally not recommended except in high-risk situations such as diabetes or prior MI) 1, 3
• Patients weighing <60 kg (consider 5 mg maintenance dose) 3
• Patients with propensity to bleed 3
• Patients on medications that increase bleeding risk (warfarin, heparin, fibrinolytics, chronic NSAIDs) 3

Patient Selection Algorithm

1. Optimal candidates (greatest benefit):

   • Patients with ACS undergoing PCI
   • Diabetic patients (showed greater benefit in subgroup analysis) 1
   • Patients with history of prior MI 1
   • Patients at high risk for stent thrombosis

2. Contraindicated in:

   • Patients with history of stroke/TIA 1, 3
   • Patients with active bleeding 3

3. Use with caution or avoid in:

   • Elderly patients ≥75 years 3
   • Patients weighing <60 kg 3
   • Patients likely to need CABG 3

Perioperative Management

• When possible, discontinue prasugrel at least 7 days before any surgery 1
• This is longer than the 5-day washout period recommended for clopidogrel 1

Common Pitfalls to Avoid

1. Inappropriate patient selection: Carefully screen for contraindications, especially prior stroke/TIA
2. Inadequate timing: For UA/NSTEMI, administer prasugrel only after coronary anatomy is defined 1
3. Failure to adjust dosing: Consider 5 mg maintenance dose in patients <60 kg 3
4. Premature discontinuation: Stopping prasugrel prematurely increases risk of stent thrombosis and cardiovascular events 3
5. Inadequate bleeding risk assessment: Always evaluate bleeding risk before prescribing prasugrel

Prasugrel represents an important advancement in antiplatelet therapy for PCI, offering superior efficacy to clopidogrel in preventing thrombotic events, but requires careful patient selection and monitoring due to its increased bleeding risk.