Aspirin with Ticagrelor in Intracranial Stenosis
Yes, aspirin with ticagrelor is indicated for short-term use (up to 30 days) in patients with recent minor stroke or high-risk TIA (within 24 hours) who have ipsilateral intracranial stenosis ≥30%, though this carries a lower strength of recommendation (Class 2b) compared to aspirin plus clopidogrel.
Primary Recommendation Framework
The 2021 AHA/ASA guidelines provide a tiered approach to dual antiplatelet therapy (DAPT) in symptomatic intracranial atherosclerotic stenosis (ICAS):
First-Line DAPT Option
- Aspirin plus clopidogrel receives a Class 2a recommendation (reasonable) for patients with recent stroke or TIA (within 30 days) attributable to severe stenosis (70-99%) of a major intracranial artery, continued for up to 90 days 1
Alternative DAPT Option
- Aspirin plus ticagrelor 90 mg twice daily receives a Class 2b recommendation (may be considered) for patients with recent minor stroke or high-risk TIA (within 24 hours) and concomitant ipsilateral >30% stenosis of a major intracranial artery, for up to 30 days 1
Evidence Supporting Ticagrelor Use
THALES Trial Subgroup Analysis
The key evidence comes from a prespecified subgroup analysis of patients with ipsilateral atherosclerosis including ICAS 1:
Efficacy: Among patients with ≥30% intracranial stenosis ipsilateral to the ischemic event, the risk of recurrent stroke or death at 30 days was 9.9% with ticagrelor 90 mg twice daily plus aspirin 100 mg daily versus 15.2% with aspirin alone (HR 0.66,95% CI 0.47-0.93, P=0.016) 1
Safety: Bleeding events in the ipsilateral atherosclerosis subgroup treated with ticagrelor and aspirin were not significantly higher than aspirin alone, contrasting with the overall THALES population without atherosclerosis 1
Important caveats: THALES required loading doses of both ticagrelor and aspirin, and ICAS was not required to be related to the index ischemic event, so some patients may not have had symptomatic ICAS 1
Clinical Decision Algorithm
When to Choose Ticagrelor Over Clopidogrel
Given the lack of comparative data between dual-antiplatelet regimens in ICAS, the choice should be based on 1:
Timing considerations: Ticagrelor is specifically supported for hyperacute presentation (within 24 hours), while clopidogrel has broader evidence for use within 30 days 1
Stenosis severity: Clopidogrel has stronger evidence (Class 2a) for severe stenosis (70-99%), while ticagrelor evidence includes moderate stenosis (≥30%) 1
Treatment duration: Ticagrelor regimen is limited to 30 days, while clopidogrel can be continued up to 90 days 1
Patient adherence factors: Consider medication cost and dose frequency (ticagrelor requires twice-daily dosing versus once-daily clopidogrel) 1
Critical Safety Considerations
Aspirin Dosing
- When using ticagrelor, aspirin maintenance dose should be limited to ≤100 mg daily, as higher doses both decrease effectiveness and increase bleeding risk 2
Contraindications
- Ticagrelor is absolutely contraindicated in patients with active bleeding or history of intracranial hemorrhage per FDA boxed warning 2
- Patients with prior stroke or TIA represent a high-risk group for intracranial bleeding when receiving DAPT 2
Procedural Management
- Ticagrelor should be discontinued at least 5 days before any surgical procedure to reduce bleeding risk 2
Alternative DAPT Regimens
Cilostazol-Based Therapy
- Aspirin plus cilostazol receives a Class 2b recommendation and may be considered to reduce recurrent stroke risk in patients with 50-99% stenosis 1
- Asian population studies showed cilostazol plus aspirin or clopidogrel reduced stroke rates (4% vs 9.2%, HR 0.47,95% CI 0.23-0.95) without excess bleeding 3
- Cilostazol combinations were more effective than aspirin monotherapy in preventing stenosis progression 4
Common Pitfalls to Avoid
Do not use warfarin: Aspirin 325 mg daily is recommended in preference to warfarin (Class 1 recommendation) to reduce recurrent ischemic stroke and vascular death in patients with 50-99% stenosis 1
Do not perform early stenting: Angioplasty and stenting should not be performed as initial treatment in patients with severe stenosis (70-99%), even for those already on antithrombotic therapy at the time of stroke or TIA (Class 3: Harm) 1
Avoid excessive aspirin doses: Higher aspirin doses with ticagrelor increase bleeding without improving efficacy 2
Do not overlook risk factor management: Blood pressure control (SBP <140 mm Hg), high-intensity statin therapy, and at least moderate physical activity are Class 1 recommendations alongside antiplatelet therapy 1