For a patient with coronary artery disease undergoing percutaneous coronary intervention for acute coronary syndrome, should I choose Brilinta (ticagrelor) or prasugrel considering age, body weight, bleeding risk, prior stroke or transient ischemic attack, and renal function?

Choosing Between Brilinta (Ticagrelor) and Prasugrel in CAD Patients After PCI for ACS

For most CAD patients undergoing PCI for ACS, ticagrelor (Brilinta) is the preferred first-line P2Y12 inhibitor because it can be started immediately upon ACS diagnosis, reduces all-cause mortality, and has no absolute contraindications based on stroke history, age, or weight. 1, 2

Decision Algorithm Based on Patient Characteristics

Absolute Contraindications That Force Your Choice

If the patient has ANY prior stroke or TIA (even decades ago):

• Use ticagrelor – prasugrel is absolutely contraindicated (Class III Harm) regardless of how remote the stroke was 1, 2
• Prasugrel increases cerebrovascular bleeding and worsens net clinical outcomes in this population (HR 1.54, P=0.04) 1
• Never use prasugrel – this is an FDA black-box warning with no temporal exemption 1

If the patient has prior intracranial hemorrhage:

• Use prasugrel or clopidogrel – ticagrelor is contraindicated 2, 3

If the patient has active pathological bleeding:

• Neither agent should be used until bleeding is controlled 1, 2

Age and Weight Considerations

Age ≥75 years:

• Prefer ticagrelor – prasugrel shows no net benefit and increased fatal/intracranial bleeding risk in this age group (HR 0.99, P=0.92) 1
• Exception: Consider prasugrel only if the patient has both diabetes AND prior MI, where benefit may outweigh risk 1

Body weight <60 kg:

• Prefer ticagrelor – prasugrel shows no net benefit (HR 1.03, P=0.89) and increased bleeding due to higher drug exposure 1
• If prasugrel must be used, reduce dose to 5 mg daily (though this dose lacks prospective validation) 1

Timing and Coronary Anatomy Considerations

When coronary anatomy is UNKNOWN (before angiography):

• Use ticagrelor – it can be started immediately upon ACS diagnosis 2, 3
• Do NOT use prasugrel – it must only be given after coronary anatomy is defined and PCI is confirmed (Class III recommendation) 1, 2

When coronary anatomy IS KNOWN and PCI is planned:

• Either agent is acceptable, but prasugrel may be preferred in this specific scenario 2
• Give prasugrel 60 mg loading dose at the time of or within 1 hour after PCI 2

Special Clinical Situations Favoring Prasugrel

Diabetes mellitus:

• Prasugrel shows greater relative benefit (12.2% vs 17.0% primary endpoint, HR 0.70, P=0.001) 1

Prior myocardial infarction:

• Prasugrel demonstrates enhanced efficacy in this subgroup 1

High ischemic risk with low bleeding risk:

• Prasugrel may provide superior ischemic protection (9.9% vs 12.1% primary endpoint, HR 0.81, P<0.001) 1

Special Clinical Situations Favoring Ticagrelor

Need for urgent CABG:

• Use ticagrelor – can be stopped 5 days before surgery vs 7 days for prasugrel 2, 3

Requirement for oral anticoagulation (triple therapy):

• Switch to clopidogrel – both ticagrelor and prasugrel carry excessive bleeding risk in this setting 2, 3

Conservative (non-invasive) management strategy:

• Use ticagrelor – prasugrel has not been studied in ACS patients managed without PCI 2

Renal dysfunction:

• Either agent is acceptable – no dose adjustment needed for ticagrelor; prasugrel dosing unchanged 2

Dosing Regimens

Ticagrelor:

• Loading: 180 mg orally immediately upon ACS diagnosis 1, 2, 3
• Maintenance: 90 mg twice daily for 12 months 1, 2, 3
• Aspirin: 75-100 mg daily (never exceed 100 mg – FDA black-box warning) 1, 2, 3

Prasugrel:

• Loading: 60 mg orally after coronary anatomy is known 1, 2
• Maintenance: 10 mg once daily for 12 months (5 mg daily if <60 kg) 1, 2
• Aspirin: 75-100 mg daily 2, 3

Bleeding Risk Mitigation (Mandatory for Both Agents)

All patients must receive:

• Proton pump inhibitor (pantoprazole 40 mg daily preferred) – Class I recommendation 2, 3
• Low-dose aspirin only (75-100 mg daily) 1, 2, 3
• Radial artery access for PCI when performed by experienced operator 2, 3

High bleeding risk patients (PRECISE-DAPT score ≥25):

• Consider shortening DAPT duration to 6 months 1, 3
• Prasugrel may trend toward lower bleeding than ticagrelor in this subgroup 4

Critical Pitfalls to Avoid

Never discontinue DAPT within the first 30 days after stent placement – this dramatically increases stent thrombosis, MI, and death risk 2, 3

Never give prasugrel before knowing coronary anatomy – this is a Class III recommendation 1, 2

Never use prasugrel in patients with any prior stroke/TIA – absolute contraindication with no exceptions 1, 2

Never exceed 100 mg daily aspirin with ticagrelor – higher doses blunt ticagrelor's antiplatelet effect 1, 2, 3

Never omit a PPI when prescribing DAPT – this significantly increases GI bleeding 2, 3

Comparative Efficacy and Safety

Ticagrelor advantages:

• Reduces all-cause mortality (4.5% vs 5.9%, P<0.001) 1
• No contraindications based on age, weight, or prior ischemic stroke 1, 2
• Can be started immediately before angiography 2, 3
• Shorter discontinuation time before surgery (5 vs 7 days) 2, 3

Prasugrel advantages:

• May provide superior ischemic protection in selected patients 1
• Once-daily dosing may improve compliance 2
• Greater benefit in diabetes and prior MI subgroups 1

Bleeding comparison:

• Prasugrel: 2.4% TIMI major bleeding (1.32 HR vs clopidogrel) 1
• Ticagrelor: Similar overall TIMI major bleeding to clopidogrel, but higher non-CABG bleeding 5
• Both increase bleeding vs clopidogrel, but mortality benefit with ticagrelor outweighs this risk 1, 6