What alternative antiplatelet therapy should be used for a patient with acute coronary syndrome (NSTEMI or STEMI) when ticagrelor is unavailable?

Alternative P2Y12 Inhibitors When Ticagrelor Is Unavailable

When ticagrelor is unavailable for acute coronary syndrome, use prasugrel (60 mg loading, then 10 mg daily) as the first alternative for patients undergoing PCI, or clopidogrel (600 mg loading, then 75 mg daily) for all other situations. 1

Clinical Decision Algorithm

For STEMI or NSTEMI Patients Undergoing PCI

First-line alternative: Prasugrel 1

• Loading dose: 60 mg orally at the time of PCI (after coronary anatomy is known) 1
• Maintenance dose: 10 mg daily for 12 months 1
• Efficacy: Prasugrel reduces MACE and stent thrombosis comparably to ticagrelor in PCI patients 1

Absolute contraindications to prasugrel: 1, 2

• Prior stroke or TIA at any time (even decades ago) – this increases cerebrovascular bleeding risk (6.5% vs 1.2% with clopidogrel) and worsens net clinical outcomes 1, 3
• Active pathological bleeding 2
• Patients likely to require urgent CABG 2

Relative contraindications (use 5 mg maintenance dose or avoid): 1, 2

• Age ≥75 years (increased fatal and intracranial bleeding risk) 2
• Body weight <60 kg (increased bleeding risk; consider 5 mg maintenance dose) 1, 2

For Patients NOT Undergoing PCI (Medical Management Only)

Use clopidogrel – prasugrel is absolutely contraindicated 1, 4

• Loading dose: 600 mg orally 1
• Maintenance dose: 75 mg daily for 12 months 1
• Rationale: Prasugrel has never been studied in non-PCI ACS patients; the TRILOGY-ACS trial showed no benefit and prasugrel is not indicated without planned PCI 4

For STEMI Managed with Fibrinolytic Therapy

Use clopidogrel exclusively 1

• Loading dose: 300 mg if age ≤75 years; 75 mg if age >75 years 1
• Maintenance dose: 75 mg daily 1
• Duration: Minimum 14 days, ideally 12 months 5
• Evidence: Clopidogrel reduces 30-day MACE and improves survival when combined with fibrinolytics 1

For Patients with Prior Stroke or TIA

Use clopidogrel only 1, 5

• Prasugrel is absolutely contraindicated regardless of how remote the stroke/TIA occurred 1, 2
• Clopidogrel 600 mg loading, then 75 mg daily is the only acceptable P2Y12 inhibitor alternative 1

Essential Adjunctive Therapy

All patients on dual antiplatelet therapy must receive: 1, 5

• Aspirin 75-100 mg daily (never exceed 100 mg) 1
• Proton pump inhibitor (Class I recommendation) to reduce gastrointestinal bleeding 1, 5
  • Pantoprazole 40 mg daily is preferred due to lowest CYP2C19 inhibition and no attenuation of clopidogrel efficacy 5, 6

Standard Duration of Therapy

12 months of dual antiplatelet therapy is mandatory for all ACS patients regardless of: 1, 5

• ACS subtype (STEMI, NSTEMI, unstable angina) 1
• Stent type (drug-eluting or bare-metal) 1
• Management strategy (PCI, CABG, or medical therapy alone) 1, 5

Exception: High bleeding-risk patients (PRECISE-DAPT score ≥25) may shorten to 6 months 1

Critical Timing Considerations

Prasugrel Administration Timing

• Do NOT give prasugrel before coronary anatomy is known (Class III recommendation) 1, 4
• Administer loading dose only after diagnostic angiography confirms PCI will be performed 1, 4
• The ACCOAST trial showed upstream prasugrel (before angiography) increased bleeding without ischemic benefit 4

Clopidogrel Administration Timing

• Can be given immediately upon ACS diagnosis, before angiography 1
• Provides flexibility for both invasive and non-invasive management strategies 1

Comparative Efficacy and Safety

Clopidogrel is less potent than ticagrelor or prasugrel: 1, 7

• Requires hepatic biotransformation, causing delayed onset (2 hours vs 30 minutes) 3, 8
• High on-treatment platelet reactivity in 30-40% of patients (vs 3% with prasugrel/ticagrelor) 3
• Modest absolute increase of 2-3% in MACE over 12 months compared to newer agents 5, 7
• However: Substantially lower bleeding risk, making it preferred for high bleeding-risk patients 1, 5

Prasugrel provides potent, rapid platelet inhibition: 7, 3, 9

• More consistent antiplatelet effect than clopidogrel 7, 8
• Reduces MACE and stent thrombosis comparably to ticagrelor in PCI patients 1
• ISAR-REACT-5 trial showed prasugrel reduced death/MI/stroke vs ticagrelor (6.9% vs 9.3%, P=0.006) with similar bleeding 3

Common Pitfalls to Avoid

• Never discontinue dual antiplatelet therapy within the first 30 days after stent placement – this dramatically increases stent thrombosis, MI, and death risk 1, 5
• Never give prasugrel to patients with prior stroke/TIA – this is an absolute contraindication with no temporal exemption 1, 2, 3
• Never give prasugrel before knowing coronary anatomy – wait until angiography confirms PCI will be performed 1, 4
• Never omit a PPI when prescribing dual antiplatelet therapy – this significantly reduces GI bleeding 1, 5
• Never use aspirin >100 mg daily with any P2Y12 inhibitor – higher doses increase bleeding without improving efficacy 1, 5
• Never use prasugrel for medical management without PCI – it is contraindicated and has no proven benefit 1, 4

Special Scenario: Triple Therapy (Oral Anticoagulation Required)

Switch to clopidogrel if oral anticoagulation is needed: 1, 5

• Discontinue aspirin 1-4 weeks after PCI 1, 5
• Continue clopidogrel (not prasugrel or ticagrelor) plus anticoagulant 1, 5
• Clopidogrel has substantially lower bleeding risk in triple-therapy settings 1, 5