Is prasugrel indicated only for acute coronary syndrome patients after percutaneous coronary intervention?

Prasugrel Indication: Not Limited to Post-PCI Patients

Prasugrel is FDA-approved for acute coronary syndrome (ACS) patients who are to be managed with percutaneous coronary intervention (PCI)—meaning the decision to proceed with PCI must be made before prasugrel is administered, but the drug is not restricted to patients who have already undergone PCI. 1

FDA-Approved Indications

Prasugrel is indicated for the reduction of thrombotic cardiovascular events in two specific ACS populations 1:

• Unstable angina or non-ST-elevation myocardial infarction (NSTEMI) patients who are to be managed with PCI 1
• ST-elevation myocardial infarction (STEMI) patients when managed with either primary or delayed PCI 1

Critical Timing Requirement: Coronary Anatomy Must Be Known

The pivotal distinction is that prasugrel must be administered after coronary anatomy has been defined—meaning after diagnostic angiography has identified the coronary lesions and confirmed that PCI will be performed. 2 This is fundamentally different from ticagrelor, which can be given immediately upon ACS diagnosis before any invasive procedure. 3

• The TRITON-TIMI 38 trial protocol specified that prasugrel loading dose was administered before, during, or within 1 hour after PCI, but only after coronary anatomy had been defined. 2
• Prasugrel should not be administered before coronary anatomy is known (Class III recommendation). 2, 3
• This restriction exists because prasugrel increases bleeding risk, and patients may require urgent coronary artery bypass grafting (CABG) once anatomy is visualized—prasugrel must be discontinued at least 7 days before CABG. 1

Why Prasugrel Is Not for Medically Managed ACS

Prasugrel has not been studied and is not recommended for ACS patients managed with medical therapy alone (without PCI). 2, 4 The TRITON-TIMI 38 trial enrolled only patients who were referred for PCI, and the FDA approval reflects this population. 2, 1

• The European Society of Cardiology explicitly states that prasugrel is not recommended for medically managed ACS patients. 2, 4
• If a patient presents with ACS and the management strategy is uncertain or medical therapy is planned, ticagrelor is the preferred P2Y12 inhibitor because it has been studied in all ACS patients regardless of management strategy. 2, 3

Practical Clinical Algorithm

When to use prasugrel:

1. Patient presents with ACS (unstable angina, NSTEMI, or STEMI). 1
2. Diagnostic coronary angiography is performed and identifies lesions amenable to PCI. 2
3. Decision is made to proceed with PCI (either immediately or staged). 1
4. At this point—after anatomy is known and PCI is planned—administer prasugrel 60 mg loading dose. 2, 1
5. Continue prasugrel 10 mg daily for 12 months. 2, 1

When NOT to use prasugrel:

• Before coronary angiography (use ticagrelor instead for upstream therapy). 2, 3
• In patients managed with medical therapy alone without PCI. 2, 4
• In patients with prior stroke or TIA (absolute contraindication). 2, 1
• In patients likely to require urgent CABG. 1

Comparison with Ticagrelor

Ticagrelor is the preferred first-line P2Y12 inhibitor for ACS because it can be administered immediately upon diagnosis, before coronary anatomy is known, and is effective regardless of whether the patient undergoes PCI, medical management, or CABG. 2, 3 Prasugrel is reserved for the specific scenario where PCI is planned and coronary anatomy has been defined. 2, 3

• The 2020 ESC guidelines recommend against pre-treatment with prasugrel in NSTE-ACS patients (before angiography), citing the ACCOAST trial which showed no ischemic benefit but substantially higher bleeding risk. 2
• Prasugrel should be considered the preferred P2Y12 inhibitor for NSTE-ACS patients who proceed to PCI after anatomy is known. 2

Common Pitfall to Avoid

Do not administer prasugrel upstream (before angiography) in ACS patients. 2, 3 This practice increases bleeding risk without ischemic benefit and may delay or complicate urgent CABG if needed. 2, 1 If upstream P2Y12 inhibition is desired, use ticagrelor 180 mg loading dose instead. 2, 3