What alternative antiplatelet agent can be used for a patient with an extremely high risk of stroke, subtherapeutic P2Y12 inhibition despite compliance with Clopidogrel, and experiencing shortness of breath with Brillinta (Ticagrelor)?

Switch to Prasugrel for High Stroke Risk Patient with Ticagrelor Intolerance

For a patient with extremely high stroke risk, subtherapeutic P2Y12 inhibition on clopidogrel, and shortness of breath on ticagrelor (Brillinta), prasugrel is the recommended alternative P2Y12 inhibitor, provided the patient has no history of stroke or TIA and weighs ≥60 kg. 1

Critical Contraindication Assessment First

Before switching to prasugrel, you must verify the patient does NOT have:

• History of stroke or TIA (absolute contraindication - prasugrel is Class III: Harm) 1
• Body weight <60 kg (increased bleeding risk; if present, use 5 mg maintenance dose instead of 10 mg) 1
• Age ≥75 years (generally not recommended except in high-risk situations like diabetes or prior MI, where benefit may outweigh risk) 1
• Active pathological bleeding 1

Prasugrel Dosing and Administration

Loading and maintenance:

• 60 mg loading dose (after coronary anatomy is known if post-PCI) 1
• 10 mg daily maintenance dose (or 5 mg daily if weight <60 kg) 1
• Continue for at least 12 months in ACS patients 1

Why Prasugrel Over Other Options

Prasugrel advantages in your scenario:

• More potent and consistent P2Y12 inhibition than clopidogrel, addressing the subtherapeutic inhibition problem 1, 2
• Reduced major cardiovascular events (9.9% vs 12.1% with clopidogrel, HR 0.81, P<0.001) in ACS patients undergoing PCI 1
• No dyspnea side effect unlike ticagrelor, which causes dyspnea in approximately 14% of patients 3
• Rapid onset with more predictable antiplatelet response than clopidogrel 2, 4

Trade-off to discuss with patient:

• Prasugrel increases major bleeding compared to clopidogrel (2.4% vs 1.8%, P<0.001) 1
• Fatal bleeding increased (0.4% vs 0.1%) 1

Alternative if Prasugrel is Contraindicated

If the patient has prior stroke/TIA or other prasugrel contraindications:

Option 1: Return to clopidogrel with platelet function testing

• Resume clopidogrel 75 mg daily 1
• Consider platelet function testing to guide dose adjustment or identify clopidogrel resistance 1
• De-escalation strategies guided by platelet function testing received Class IIb recommendation in 2018 ESC guidelines 1

Option 2: Aspirin plus dipyridamole (for stroke prevention specifically)

• Aspirin 25 mg + extended-release dipyridamole 200 mg twice daily 1, 5
• This combination is specifically recommended for non-cardioembolic stroke/TIA secondary prevention 1, 6
• Equivalent efficacy to clopidogrel for stroke prevention (HR 1.01,95% CI 0.92-1.11) 1

Bridging Strategy During Transition

If transitioning from ticagrelor to prasugrel:

• Wait 24 hours after last ticagrelor dose before administering prasugrel loading dose 1
• Give prasugrel 60 mg loading dose followed by 10 mg daily 1
• This prevents gaps in P2Y12 inhibition during the acute period 1

Monitoring for Bleeding Risk

Enhanced bleeding surveillance needed because:

• Prasugrel increases non-CABG major bleeding (2.4% vs 1.8%) 1
• Patient already demonstrated intolerance to one P2Y12 inhibitor 1
• Extremely high stroke risk suggests likely multiple comorbidities 1

Specific monitoring:

• Assess for concomitant anticoagulant use (warfarin, heparin) - increases bleeding risk 1
• Check for chronic NSAID use - increases bleeding risk 1
• Consider proton pump inhibitor for GI bleeding prophylaxis 1

If All P2Y12 Inhibitors Fail or Are Contraindicated

Last resort option: Aspirin monotherapy

• 81-100 mg daily 1
• Less effective than dual antiplatelet therapy but reduces stroke risk by 12% compared to placebo 1
• Recommended when P2Y12 inhibitors cannot be tolerated 1

Critical Pitfall to Avoid

Do NOT use ticagrelor and prasugrel simultaneously - no data support dual P2Y12 inhibitor therapy and this dramatically increases bleeding risk without proven benefit 1