In an acute coronary syndrome patient who will not undergo percutaneous coronary intervention, should prasugrel be used?

Prasugrel Is Not Indicated for ACS Patients Who Will Not Undergo PCI

Prasugrel is absolutely contraindicated in acute coronary syndrome patients who will not be treated with percutaneous coronary intervention. 1, 2

Why Prasugrel Requires PCI

• The FDA label explicitly restricts prasugrel to ACS patients "who are to be managed with percutaneous coronary intervention" – this is the only approved indication. 2

• Prasugrel has not been studied and is not recommended for ACS patients managed medically without PCI. 1, 3, 4

• The pivotal TRITON-TIMI 38 trial that established prasugrel's efficacy deliberately administered the drug only after coronary angiography confirmed that PCI would be performed – patients managed conservatively were excluded from receiving prasugrel. 1, 4, 2, 5

• The TRILOGY ACS trial compared prasugrel versus clopidogrel in NSTE-ACS patients treated with an ischemia-guided (non-invasive) strategy and found no benefit of prasugrel over clopidogrel, with similar bleeding rates. 1

The Correct P2Y12 Inhibitor for Non-PCI ACS Patients

For ACS patients who will not undergo PCI, ticagrelor (180 mg loading, then 90 mg twice daily) is the first-line P2Y12 inhibitor. 1, 3, 6

• Ticagrelor is effective regardless of management strategy – it reduces major adverse cardiovascular events and mortality in both invasively managed and medically managed ACS patients. 1, 3

• The PLATO trial demonstrated ticagrelor's superiority over clopidogrel in the 28% of patients who did not undergo revascularization, with consistent reductions in cardiovascular death, myocardial infarction, and stroke. 1

• Clopidogrel (600 mg loading, then 75 mg daily) is the alternative when ticagrelor is unavailable, not tolerated, or contraindicated. 1, 3

Critical Algorithm for P2Y12 Inhibitor Selection in ACS

Step 1: Determine Revascularization Strategy

• If PCI is planned or performed → Ticagrelor or prasugrel (after anatomy is known). 1, 3
• If CABG is planned → Ticagrelor or clopidogrel (prasugrel contraindicated). 1, 3, 4
• If medical management only (no revascularization) → Ticagrelor or clopidogrel (prasugrel contraindicated). 1, 3

Step 2: Check Absolute Contraindications

• Prior stroke or TIA → Never use prasugrel (Class III Harm); use ticagrelor. 1, 3, 2
• Active bleeding or intracranial hemorrhage → Never use ticagrelor or prasugrel; use clopidogrel if DAPT is still indicated. 1, 3, 2

Step 3: Assess Bleeding Risk

• High bleeding risk or need for oral anticoagulation → Clopidogrel preferred over ticagrelor or prasugrel. 1, 3, 6

Duration of Dual Antiplatelet Therapy

• All ACS patients should receive 12 months of DAPT (aspirin 75–100 mg daily plus a P2Y12 inhibitor) regardless of whether they undergo PCI, medical therapy, or CABG. 1, 3, 6

• Prescribe a proton pump inhibitor to all patients on DAPT to reduce gastrointestinal bleeding risk – this is a Class I recommendation. 1, 3, 6

Common Pitfalls to Avoid

• Never prescribe prasugrel to ACS patients who will not undergo PCI – it is not indicated, not studied, and not recommended in this population. 1, 3, 4, 2

• Never assume that prasugrel can be used "just in case" PCI might happen later – the drug should only be given after coronary anatomy is defined and PCI is confirmed. 1, 4, 2

• Never discontinue DAPT prematurely in any ACS patient – all ACS patients require 12 months of dual antiplatelet therapy to reduce recurrent ischemic events, regardless of revascularization strategy. 1, 3