What is the recommended dosage and duration of Prasugrel (prasugrel) therapy post-stent placement?

Prasugrel Post-Stent Therapy: Dosing and Duration

For patients with acute coronary syndrome (ACS) undergoing PCI with stent placement, administer prasugrel as a 60 mg loading dose followed by 10 mg daily maintenance for at least 12 months, combined with low-dose aspirin (81 mg daily). 1, 2

Loading Dose Administration

• Give 60 mg loading dose after coronary anatomy is defined in UA/NSTEMI patients, not before diagnostic angiography 1, 2
• For STEMI patients presenting within 12 hours of symptom onset, the loading dose may be given at diagnosis, though most receive it at the time of PCI 2
• Early administration before angiography increases bleeding risk in patients requiring urgent CABG without clear benefit 2

Maintenance Dosing

Standard dose: 10 mg once daily 1, 2

Dose Reductions Required:

• Patients <60 kg body weight: Consider reducing to 5 mg daily due to increased active metabolite exposure and bleeding risk 1, 3, 2
• Patients ≥75 years: Generally not recommended except in high-risk situations (diabetes or prior MI), where 5 mg may be considered 1, 3, 2

Duration of Therapy

Minimum 12 months for all stent types (BMS or DES) in ACS patients 1

• After 12 months, continuation beyond may be reasonable in patients who tolerate DAPT without bleeding complications and are not at high bleeding risk 1
• Recent evidence from the 4D-ACS trial suggests 1-month DAPT followed by prasugrel 5 mg monotherapy may reduce bleeding without compromising ischemic outcomes, though this represents emerging data 4
• The TAXUS Liberté substudy showed continued benefit with 30 months of prasugrel therapy, with reduced MI and stent thrombosis rates 5

Aspirin Co-Administration

• 81 mg daily aspirin (range 75-100 mg) is the recommended dose when combined with prasugrel 1
• Aspirin should be continued indefinitely after PCI 1

Absolute Contraindications

Do not use prasugrel in patients with: 1, 2

• Prior history of stroke or TIA (Class III: Harm recommendation)
• Active pathological bleeding
• Patients likely to undergo urgent CABG

Perioperative Management

• Discontinue prasugrel at least 7 days before elective surgery 1, 3, 2
• For urgent/emergent surgery within the first 6 months post-stent, continuing DAPT should be strongly considered given the catastrophic risk of stent thrombosis 6
• The risk of stent thrombosis far outweighs bleeding risk except in intracranial procedures 6

Early Discontinuation Considerations

• May discontinue after 6 months only if patient develops high bleeding risk (e.g., requiring oral anticoagulation), faces high risk of severe bleeding complications (e.g., major intracranial surgery), or develops significant overt bleeding 1
• Discontinuing prasugrel, particularly in the first weeks after ACS, substantially increases risk of subsequent cardiovascular events 2

Bleeding Risk Factors

Additional factors increasing bleeding risk include: 1, 3, 2

• Body weight <60 kg
• Concomitant use of warfarin, heparin, fibrinolytics, or chronic NSAIDs
• Propensity to bleed
• Advanced age (≥75 years)

Key Safety Data

• Prasugrel reduces ischemic events (9.9% vs 12.1% with clopidogrel) but increases major bleeding (2.4% vs 1.8%) and fatal bleeding (0.4% vs 0.1%) 7
• In patients with prior stroke/TIA, prasugrel caused 6.5% stroke rate (including 2.3% intracranial hemorrhage) versus 1.2% with clopidogrel 2
• Suspect bleeding in any hypotensive patient recently undergoing coronary procedures while on prasugrel 2