What is the protocol for using Ticagrelor (ticagrelor) in patients with posterior circulation stroke?

Ticagrelor Protocol for Posterior Circulation Stroke

For patients with acute minor posterior circulation stroke or TIA, dual antiplatelet therapy with ticagrelor plus aspirin for 30 days is recommended based on the THALES trial, using a 180 mg loading dose of ticagrelor followed by 90 mg twice daily, combined with aspirin 300-325 mg loading dose then 75-100 mg daily. 1

Evidence Supporting Use in Posterior Circulation

• Stroke recurrence rates are similar between posterior and anterior circulation strokes (7.4% vs 8.3%), indicating that posterior circulation location does not confer different risk profiles. 2

• Ticagrelor-aspirin significantly reduces stroke recurrence in posterior circulation infarcts compared to clopidogrel-aspirin (hazard ratio 0.59,95% CI 0.40-0.89, P=0.01), with similar efficacy to anterior circulation strokes. 2

• There is no treatment-by-infarct location interaction (P=0.92), meaning ticagrelor works equally well regardless of whether the stroke is posterior or anterior circulation. 2

Specific Dosing Protocol

Loading Phase (Day 1):

• Ticagrelor: 180 mg loading dose 1, 3
• Aspirin: 300-325 mg loading dose 1, 3

Maintenance Phase (Days 2-30):

• Ticagrelor: 90 mg twice daily 1, 3
• Aspirin: 75-100 mg daily 1, 3

After 30 Days:

• Switch to single antiplatelet therapy (aspirin or clopidogrel) 3

Patient Selection Criteria

Appropriate Candidates:

• Minor stroke (non-severe) or high-risk TIA 1
• Symptom onset within 24 hours 4
• Non-cardioembolic mechanism 4
• No contraindications to dual antiplatelet therapy 1

Absolute Contraindications:

• Active bleeding 5
• History of intracranial hemorrhage 5
• Patients requiring thrombolysis (relative contraindication - see below) 6

Critical Safety Considerations

Bleeding Risk Profile:

• Intracranial hemorrhage occurs in 0.4% with ticagrelor-aspirin vs 0.1% with aspirin alone (P=0.01), representing a 4-fold increase. 1, 3
• Severe bleeding occurs in 0.5% vs 0.1% (P=0.001). 1
• The number needed to harm for severe bleeding is 263. 1, 3
• Any bleeding risk increases in both posterior and anterior circulation patients on ticagrelor-aspirin (P=0.02 for posterior circulation). 2

High-Risk Populations to Avoid:

• Patients with prior stroke or TIA have undetermined risk of intracranial hemorrhage and should be approached with extreme caution. 1, 5
• Elderly patients and those with fall risk require careful risk-benefit assessment. 5

Special Scenario: Ipsilateral Atherosclerotic Stenosis

Enhanced benefit in atherosclerotic disease:

• For patients with ≥30% intracranial stenosis ipsilateral to the ischemic event, ticagrelor-aspirin reduces stroke/death from 15.2% to 9.9% (HR 0.66,95% CI 0.47-0.93). 1
• Critically, bleeding events were NOT significantly higher in this atherosclerotic subgroup, making the risk-benefit ratio more favorable. 1, 3
• This represents the strongest indication for ticagrelor use in posterior circulation stroke. 1

Thrombolysis Considerations

If thrombolysis is being considered:

• Ticagrelor is not an absolute contraindication to IV alteplase, but safety is not well established. 6
• Only 7 total cases reported in literature, with 4 of 5 prior cases experiencing hemorrhagic complications. 6
• Two successful posterior circulation cases treated with alteplase on ticagrelor without bleeding have been reported. 6
• Decision must be made case-by-case, weighing severity of deficit against hemorrhagic risk. 6

Perioperative Management

• Discontinue ticagrelor at least 5 days before any planned surgery to reduce bleeding risk. 1, 5
• This is critical for posterior fossa procedures where even minor bleeding can be catastrophic. 1

Comparison to Alternative Regimens

Ticagrelor monotherapy (without aspirin):

• Not superior to aspirin alone for stroke prevention. 1
• Should not be used as monotherapy in acute setting. 1

Clopidogrel-aspirin alternative:

• Both regimens effective, but choice should consider medication adherence (ticagrelor requires twice-daily dosing vs once-daily clopidogrel). 1
• Cost and dosing frequency favor clopidogrel for some patients. 1
• Genetic testing for CYP2C19 variants may inform choice but is not routinely recommended. 1

Common Pitfalls to Avoid

• Do not use aspirin >100 mg daily with ticagrelor - higher doses decrease effectiveness and increase bleeding. 5, 7
• Do not continue dual therapy beyond 30 days - hemorrhage risk outweighs benefit after this period. 1
• Do not use in patients with prior intracranial hemorrhage - this is an absolute contraindication per FDA boxed warning. 5
• Do not assume posterior circulation strokes have different recurrence risk - they behave similarly to anterior circulation. 2