Is prasugrel (P2Y12 inhibitor) monotherapy effective for patients with acute coronary syndrome (ACS)?

Prasugrel Monotherapy for Acute Coronary Syndrome

Prasugrel monotherapy is not recommended for patients with acute coronary syndrome (ACS). Current guidelines strongly support dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor as the standard of care for ACS patients, rather than P2Y12 inhibitor monotherapy 1.

Current Guideline Recommendations

Standard DAPT Approach

• DAPT with aspirin and a P2Y12 inhibitor (prasugrel, ticagrelor, or clopidogrel) is the cornerstone treatment for ACS patients 1
• For patients undergoing percutaneous coronary intervention (PCI), DAPT is recommended for at least 12 months 1
• Prasugrel is specifically indicated to reduce thrombotic cardiovascular events in ACS patients managed with PCI 2

Prasugrel-Specific Recommendations

• Prasugrel is administered as a 60 mg loading dose followed by 10 mg daily maintenance dose, always in combination with aspirin (75-325 mg daily) 2
• It is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 treatment in ACS patients undergoing PCI who are not at high risk for bleeding complications 1
• Prasugrel should not be administered to patients with a prior history of stroke or transient ischemic attack 1, 2

Evidence on Prasugrel Efficacy

Prasugrel has demonstrated superior efficacy compared to clopidogrel in ACS patients undergoing PCI:

• The TRITON-TIMI 38 trial showed that prasugrel reduced the primary efficacy endpoint (cardiovascular death, nonfatal MI, or nonfatal stroke) compared to clopidogrel (9.9% vs. 12.1%, HR 0.81) 3
• Significant reductions were observed in myocardial infarction (7.4% vs. 9.7%), urgent target-vessel revascularization (2.5% vs. 3.7%), and stent thrombosis (1.1% vs. 2.4%) 3
• However, prasugrel was associated with increased major bleeding (2.4% vs. 1.8%) and life-threatening bleeding (1.4% vs. 0.9%) 3

Emerging Evidence on P2Y12 Monotherapy

While some recent studies have explored P2Y12 inhibitor monotherapy, this approach typically involves:

1. Initial DAPT (aspirin + P2Y12 inhibitor)
2. Followed by discontinuation of aspirin after 1-3 months
3. Continuing P2Y12 inhibitor monotherapy

The 2025 ACC/AHA guidelines note that in patients who have tolerated DAPT with ticagrelor, transition to ticagrelor monotherapy is recommended ≥1 month after PCI 1. However, no similar recommendation exists for prasugrel monotherapy.

Important Considerations and Contraindications

• Bleeding risk: Prasugrel carries a significant bleeding risk, especially in patients ≥75 years of age, those with body weight <60 kg, and those with prior stroke/TIA 2
• Timing of discontinuation: If surgery is required, prasugrel should be discontinued at least 7 days prior when possible 2
• Weight-based dosing: Consider lowering maintenance dose to 5 mg in patients <60 kg 2

Algorithm for P2Y12 Inhibitor Selection in ACS

1. First-line options for ACS patients undergoing PCI:

   • Prasugrel (60 mg loading, 10 mg daily) - preferred for patients without high bleeding risk
   • Ticagrelor (180 mg loading, 90 mg twice daily)

2. Second-line option:

   • Clopidogrel (600 mg loading, 75 mg daily) - when prasugrel or ticagrelor are contraindicated

3. Contraindications to prasugrel:

   • Prior stroke or TIA (absolute contraindication)
   • Age ≥75 years (relative contraindication)
   • Body weight <60 kg (consider dose reduction)
   • High bleeding risk

Conclusion

Based on current guidelines and available evidence, prasugrel monotherapy is not recommended for ACS patients. The standard approach remains DAPT with aspirin plus a P2Y12 inhibitor for at least 12 months in ACS patients, particularly those undergoing PCI 1, 2. While prasugrel is an effective P2Y12 inhibitor with benefits over clopidogrel in reducing ischemic events, it should be used as part of DAPT rather than as monotherapy.