What is the indication for using aspirin with ticagrelor (P2Y12 inhibitor) after a stroke?

Aspirin with Ticagrelor After Stroke: Indications and Clinical Use

Aspirin combined with ticagrelor is indicated for 30 days in patients with recent (within 24 hours) minor to moderate noncardioembolic ischemic stroke (NIHSS score ≤5), high-risk TIA (ABCD2 score ≥6), or symptomatic intracranial or extracranial stenosis ≥30%, but this combination increases severe bleeding risk including intracranial hemorrhage and should be used selectively. 1

Specific Patient Populations Where Dual Therapy May Be Considered

For acute minor to moderate stroke (NIHSS ≤5):

• Initiate ticagrelor (180 mg loading dose, then 90 mg twice daily) plus aspirin (300-325 mg loading dose, then 75-100 mg daily) within 24 hours of symptom onset 1
• Continue for exactly 30 days, then transition to single antiplatelet therapy 1
• The number needed to treat is 92 to prevent one recurrent stroke, while the number needed to harm is 263 for severe bleeding 1, 2

For high-risk TIA (ABCD2 score ≥6):

• Same dosing regimen as above for 30 days 1
• This represents a more restrictive indication than aspirin-clopidogrel, which can be used for lower-risk TIA (ABCD2 ≥4) 1

For symptomatic arterial stenosis ≥30%:

• Patients with ipsilateral intracranial or extracranial stenosis accounting for the event may derive greater benefit 1
• In the atherosclerotic subgroup, ticagrelor-aspirin reduced recurrent stroke or death from 15.2% to 9.9% (hazard ratio 0.66) 2
• Notably, bleeding events were not significantly higher in this atherosclerotic subgroup compared to aspirin alone 2

Critical Safety Considerations and Contraindications

Bleeding risks that must be weighed:

• Severe bleeding occurs in 0.5% with ticagrelor-aspirin versus 0.1% with aspirin alone (P=0.001) 1, 3
• Intracranial hemorrhage risk increases from 0.1% to 0.4% (P=0.01) 1, 2
• Treatment discontinuation due to bleeding occurs in 2.8% versus 0.6% (P<0.001) 1, 2

Patients who should NOT receive ticagrelor-aspirin:

• Large strokes (NIHSS >5) have no evidence supporting dual therapy and substantially increased bleeding risk 4
• Patients requiring intracranial stenting should receive aspirin-clopidogrel, not ticagrelor, due to lack of safety data and increased hemorrhage risk 5
• Those with prior intracranial hemorrhage or high bleeding risk should receive aspirin monotherapy 2

Comparison to Aspirin-Clopidogrel Dual Therapy

Key differences in indications:

• Aspirin-clopidogrel is recommended for minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4) initiated within 12-24 hours and continued for 21-90 days 1
• Ticagrelor-aspirin has a narrower indication: NIHSS ≤5 or ABCD2 ≥6, initiated within 24 hours, for exactly 30 days 1
• Network meta-analysis shows no statistically significant difference between the two regimens (HR 0.94,95% CrI 0.78-1.13) 6
• Clopidogrel-aspirin may have lower functional disability rates compared to ticagrelor-aspirin (HR 0.85,95% CrI 0.75-0.97) 6

Practical Clinical Algorithm

Step 1: Determine stroke severity and timing

• If NIHSS >5 or >24 hours from onset → Do not use ticagrelor-aspirin 1, 4
• If NIHSS ≤5 and within 24 hours → Proceed to Step 2 1

Step 2: Assess for high-risk features

• TIA with ABCD2 ≥6, or symptomatic stenosis ≥30% → Consider ticagrelor-aspirin 1
• Ipsilateral atherosclerotic disease → Stronger consideration for ticagrelor-aspirin (greater benefit, similar bleeding risk) 2

Step 3: Evaluate bleeding risk

• Prior intracranial hemorrhage, active bleeding, or high bleeding risk → Use aspirin monotherapy instead 2
• Standard bleeding risk → May proceed with ticagrelor-aspirin 1

Step 4: Initiate therapy if appropriate

• Load with ticagrelor 180 mg plus aspirin 300-325 mg 1
• Maintain ticagrelor 90 mg twice daily plus aspirin 75-100 mg daily 1
• Continue for exactly 30 days, then switch to single antiplatelet therapy 1

Common Pitfalls to Avoid

Duration errors:

• Do not continue ticagrelor-aspirin beyond 30 days—prolonged dual therapy increases hemorrhage without additional benefit 1
• Transition to single antiplatelet therapy (aspirin or clopidogrel) after 30 days 1

Inappropriate patient selection:

• Do not use in large strokes (NIHSS >5) where bleeding risk outweighs unproven benefit 4
• Do not substitute ticagrelor-aspirin for aspirin-clopidogrel in intracranial stenting protocols 5

Timing failures:

• Initiation beyond 24 hours loses the early recurrence prevention window where benefit is demonstrated 1, 3

Alternative When Ticagrelor-Aspirin Is Not Appropriate

For minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4):

• Use aspirin-clopidogrel instead: aspirin 50-325 mg plus clopidogrel 75 mg daily for 21-90 days 1
• This has stronger evidence (Class 1, Level A-SR) compared to ticagrelor-aspirin (Class 2b, Level B-R) 1

For long-term secondary prevention after dual therapy:

• Transition to single antiplatelet therapy: aspirin 50-325 mg daily, clopidogrel 75 mg daily, or aspirin-dipyridamole 1
• Clopidogrel monotherapy may be superior to aspirin for reducing recurrent stroke and intracranial hemorrhage 7