What is the indication for Effient (prasugrel) in adult patients with acute coronary syndrome?

Indication for Effient (Prasugrel)

Effient (prasugrel) is indicated for the reduction of thrombotic cardiovascular events in patients with acute coronary syndrome (unstable angina, NSTEMI, or STEMI) who are to be managed with percutaneous coronary intervention (PCI). 1

Specific Patient Populations

Primary Indication

• Patients with unstable angina or non-ST-elevation myocardial infarction (NSTEMI) undergoing PCI 1, 2
• Patients with ST-elevation myocardial infarction (STEMI) managed with either primary or delayed PCI 1, 2

The FDA approval was based on the TRITON-TIMI 38 trial, which enrolled 13,608 patients with moderate-to-high-risk ACS scheduled for PCI, of whom 74% had UA/NSTEMI. 2

Dosing Regimen

• Loading dose: 60 mg orally as a single dose 1, 2
• Maintenance dose: 10 mg once daily 1, 2
• Reduced maintenance dose: 5 mg once daily for patients <60 kg body weight 1
• Administer with aspirin 75-325 mg daily 1, 2

Critical Timing

• Prasugrel loading dose must be administered AFTER coronary anatomy has been defined (before, during, or within 1 hour after PCI) 2
• This distinguishes prasugrel from ticagrelor, which can be given upstream before angiography 2

Absolute Contraindications

Do NOT Use Prasugrel In:

• Patients with active pathological bleeding 1
• Patients with prior transient ischemic attack (TIA) or stroke (increased risk of fatal intracranial bleeding) 1, 2, 3
• Patients with hypersensitivity to prasugrel or any component 1

High-Risk Populations Requiring Caution

Generally NOT Recommended:

• Patients ≥75 years of age (except in high-risk patients with diabetes or prior MI, where use may be considered) 1, 2
• Patients <60 kg body weight (consider 5 mg maintenance dose) 1, 3
• Patients likely to undergo urgent CABG (discontinue at least 7 days prior to surgery when possible) 1, 2

Efficacy Data

Prasugrel demonstrated superior efficacy compared to clopidogrel in the pivotal TRITON-TIMI 38 trial:

Ischemic Event Reduction:

• Primary endpoint (CV death, MI, or stroke): 9.9% vs 12.1% with clopidogrel (19% relative risk reduction, NNT=46) 2, 4
• Nonfatal MI: 7.3% vs 9.5% with clopidogrel (24% relative risk reduction) 2
• Stent thrombosis: 1.1% vs 2.4% with clopidogrel (54% relative risk reduction) 2

Bleeding Risk:

• TIMI major bleeding: 2.4% vs 1.8% with clopidogrel (32% relative risk increase, NNH=167) 2
• Fatal bleeding: 0.4% vs 0.1% with clopidogrel 2, 4
• Life-threatening bleeding: 1.4% vs 0.9% with clopidogrel 2, 4
• CABG-related major bleeding: 13.4% vs 3.2% with clopidogrel 2

Clinical Decision Algorithm

When to Choose Prasugrel Over Clopidogrel or Ticagrelor:

Use Prasugrel When:

• Patient has ACS and is P2Y12 inhibitor-naïve 2
• Coronary anatomy is known and PCI is planned 2
• Patient has NO history of stroke/TIA 1, 2
• Patient is <75 years old (or ≥75 with diabetes/prior MI) 1
• Patient weighs ≥60 kg (or use 5 mg dose if <60 kg) 1

Do NOT Use Prasugrel When:

• Patient has prior stroke/TIA (use ticagrelor instead) 1, 2
• Coronary anatomy is unknown and patient not yet committed to PCI 2
• Patient is being managed medically without PCI 2
• Patient requires oral anticoagulation (clopidogrel preferred due to lower bleeding risk) 5

Duration of Therapy

• Standard duration: 12 months of dual antiplatelet therapy 2
• Premature discontinuation increases risk of stent thrombosis, MI, and death 1

Common Pitfalls to Avoid

• Never administer prasugrel before coronary anatomy is defined (unlike ticagrelor, prasugrel should not be given upstream) 2
• Never use prasugrel in patients with prior stroke/TIA (this is an absolute contraindication due to increased fatal bleeding) 1, 2
• Never fail to reduce dose to 5 mg in patients <60 kg 1
• Never discontinue prasugrel within first month after stent placement for elective surgery (thrombotic risk is highest early) 5
• Always prescribe a proton pump inhibitor with prasugrel to reduce GI bleeding risk 5, 6