What is the recommended dosage and usage of prasugrel (Prasugrel) for patients undergoing percutaneous coronary intervention (PCI)?

Prasugrel Dosing and Administration for PCI

For patients with acute coronary syndrome undergoing PCI, initiate prasugrel with a 60 mg oral loading dose followed by 10 mg once daily maintenance, but only after coronary anatomy is defined and in P2Y12 inhibitor-naïve patients. 1, 2

Standard Dosing Regimen

• Loading dose: 60 mg orally as a single dose 1, 2
• Maintenance dose: 10 mg orally once daily 1, 2
• Duration: Continue for at least 12 months unless bleeding risk outweighs benefit 1, 3, 2
• Concomitant aspirin: 75-100 mg daily (ESC) or 75-325 mg daily (ACC/AHA) 1, 2

Critical Timing Considerations

Do not administer prasugrel until coronary anatomy is known in UA/NSTEMI patients. 1, 2 The TRITON-TIMI 38 trial, which established prasugrel's efficacy, specifically delayed loading until after diagnostic angiography in UA/NSTEMI patients to avoid exposing patients to increased bleeding risk if urgent CABG was required. 1, 2

• For UA/NSTEMI: Administer loading dose before, during, or within 1 hour after PCI, but only after coronary anatomy is established 1, 2
• For STEMI presenting within 12 hours: May administer at time of diagnosis, though most patients receive it at time of PCI 1, 2
• For STEMI presenting >12 hours after symptom onset: Wait until coronary anatomy is defined 2

Dose Adjustments for Special Populations

Low Body Weight (<60 kg)

Consider reducing maintenance dose to 5 mg daily in patients weighing <60 kg due to increased exposure to active metabolite and higher bleeding risk. 1, 4, 2 However, the 5 mg dose has not been prospectively studied for efficacy and safety. 1, 2

Elderly Patients (≥75 years)

Prasugrel is generally not recommended in patients ≥75 years due to increased risk of fatal and intracranial bleeding with uncertain benefit. 1, 4, 2 The exception is high-risk elderly patients with diabetes or prior MI, where benefit may outweigh risk and use may be considered. 1, 4, 2

Absolute Contraindications

Do not use prasugrel in patients with:

• Prior stroke or TIA at any time (Class III: Harm) 1, 5, 4, 2 In TRITON-TIMI 38, patients with prior TIA/stroke had 6.5% stroke rate on prasugrel (including 2.3% intracranial hemorrhage) versus 1.2% on clopidogrel. 1, 2
• Active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage) 2
• Hypersensitivity to prasugrel or any component 2

Surgical Considerations

Discontinue prasugrel at least 7 days before any planned surgery when possible to reduce bleeding risk. 1, 4, 2 Do not start prasugrel in patients likely to undergo urgent CABG. 1, 2 In TRITON-TIMI 38, CABG-related major bleeding was 13.4% with prasugrel versus 3.2% with clopidogrel when surgery occurred within 7 days of last dose. 1

Efficacy Data

Prasugrel demonstrated superior efficacy compared to clopidogrel in TRITON-TIMI 38 (13,608 ACS patients undergoing PCI): 1, 6

• Primary endpoint (CV death, MI, or stroke): 9.9% prasugrel vs. 12.1% clopidogrel (HR 0.81,95% CI 0.73-0.90, P<0.001) 1, 6
• Stent thrombosis: 1.1% prasugrel vs. 2.4% clopidogrel (P<0.001) 1, 3, 6
• Number needed to treat: 46 patients to prevent one event 1

Bleeding Risk

Prasugrel increases bleeding compared to clopidogrel: 1, 6

• TIMI major bleeding: 2.4% prasugrel vs. 1.8% clopidogrel (HR 1.32,95% CI 1.03-1.68, P=0.03) 1, 3, 6
• Fatal bleeding: 0.4% prasugrel vs. 0.1% clopidogrel (P=0.002) 1, 6
• Life-threatening bleeding: 1.4% prasugrel vs. 0.9% clopidogrel (HR 1.52, P=0.01) 1, 6
• Number needed to harm: 167 patients for one major non-CABG bleed 1

Additional bleeding risk factors include body weight <60 kg, propensity to bleed, and concomitant use of anticoagulants, heparin, fibrinolytics, or chronic NSAIDs. 1, 4, 2

Switching from Clopidogrel

Switching from clopidogrel to prasugrel is feasible and safe in ACS patients undergoing PCI. 7, 8 Studies show that prasugrel 60 mg loading after clopidogrel 600 mg loading does not significantly increase bleeding risk compared to prasugrel alone, though platelet inhibition may be enhanced. 7, 8

Common Pitfalls to Avoid

• Administering prasugrel before coronary anatomy is known in UA/NSTEMI patients increases bleeding risk without clear benefit 1, 2
• Using prasugrel in patients with prior stroke/TIA is contraindicated due to substantially increased stroke risk 1, 5, 4, 2
• Failing to reduce dose in patients <60 kg increases bleeding complications 1, 4, 2
• Using prasugrel in non-ACS settings lacks evidence of benefit 9
• Premature discontinuation within first few weeks increases risk of stent thrombosis, MI, and death 2