What is the recommended regimen for Prasugrel (prasugrel) in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI)?

Prasugrel Dosing and Administration in Acute Coronary Syndrome with PCI

For patients with acute coronary syndrome undergoing percutaneous coronary intervention, administer prasugrel as a 60 mg oral loading dose followed by 10 mg once daily maintenance dose, but only after coronary anatomy is defined and PCI is planned. 1, 2

Loading Dose Timing

• Do not administer prasugrel until coronary anatomy is known – this is a critical safety measure to avoid unnecessary bleeding risk in patients who may require urgent CABG 1, 2
• In NSTE-ACS patients, give the 60 mg loading dose after diagnostic angiography confirms PCI is planned, typically administered before, during, or within 1 hour after PCI 1
• In STEMI patients presenting within 12 hours of symptom onset, the loading dose may be given at time of diagnosis, though most patients receive it at the time of PCI 2
• In STEMI patients presenting more than 12 hours after symptom onset, wait until coronary anatomy is established before administering prasugrel 2

Maintenance Dose and Duration

• Continue prasugrel 10 mg once daily for 12 months as the standard duration of dual antiplatelet therapy (DAPT) with aspirin 1
• Administer aspirin 75-100 mg daily (or up to 325 mg per FDA labeling) concurrently with prasugrel 1, 2
• Prasugrel may be taken with or without food 2

Dose Adjustments for High-Risk Populations

Patients weighing <60 kg: Consider reducing maintenance dose to 5 mg daily due to increased bleeding risk, though this dose has not been prospectively validated 2

Patients ≥75 years old: Prasugrel is generally not recommended due to increased risk of fatal and intracranial bleeding, except in high-risk situations (diabetes or prior MI) where benefit may outweigh risk 2

Absolute Contraindications

• Prior stroke or transient ischemic attack – prasugrel is contraindicated due to significantly increased risk of intracranial hemorrhage 1, 2
• Active pathological bleeding (peptic ulcer, intracranial hemorrhage) 2

Preference Over Clopidogrel

Prasugrel is preferred over clopidogrel in P2Y12 inhibitor-naïve patients with ACS undergoing PCI because it reduces major adverse cardiovascular events, particularly nonfatal MI and stent thrombosis 1

• The TRITON-TIMI 38 trial demonstrated prasugrel reduced the primary endpoint (cardiovascular death, nonfatal MI, or nonfatal stroke) from 12.1% to 9.9% compared to clopidogrel (HR 0.81,95% CI 0.73-0.90, P<0.001) 1, 3
• Stent thrombosis was reduced from 2.4% to 1.1% (P<0.001) 1
• However, major bleeding increased from 1.8% to 2.4% (HR 1.32,95% CI 1.03-1.68, P=0.03), including increased fatal bleeding (0.4% vs 0.1%, P=0.002) 1, 3

Comparison with Ticagrelor

• Both prasugrel and ticagrelor are recommended in preference to clopidogrel for ACS patients undergoing PCI 1
• Prasugrel should be considered in preference to ticagrelor specifically for NSTE-ACS patients who proceed to PCI 1
• Unlike prasugrel, ticagrelor can be used in patients with prior stroke/TIA 1, 4

Surgical Considerations

• Discontinue prasugrel at least 7 days before elective surgery (including CABG) to allow antiplatelet effect to dissipate 1, 2
• Do not start prasugrel in patients likely to undergo urgent CABG 2
• In patients who underwent CABG in TRITON-TIMI 38, major bleeding was substantially higher with prasugrel (13.4% vs 3.2%, HR 4.73,95% CI 1.90-11.82, P<0.001) 1

Common Pitfalls to Avoid

• Never give prasugrel before knowing coronary anatomy – this exposes patients to bleeding risk without confirmed benefit if they require CABG instead of PCI 1, 2
• Never use prasugrel in patients with prior stroke/TIA – this is an absolute contraindication due to harm 1, 2
• Do not discontinue prasugrel prematurely – stopping within the first few weeks after ACS increases risk of subsequent cardiovascular events 2
• Do not use standard 10 mg dose in patients <60 kg without considering dose reduction to 5 mg daily 2