In an adult with a non‑cardioembolic acute ischemic stroke or high‑risk transient ischemic attack and no contraindications, can ticagrelor be used as part of dual antiplatelet therapy, and what is the recommended dosing regimen?

Ticagrelor in Acute Ischemic Stroke: Dosing and Indications

Ticagrelor combined with aspirin for exactly 30 days is recommended for adults with minor non-cardioembolic ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD² ≥4) presenting within 24 hours of symptom onset, followed by transition to single antiplatelet therapy. 1

Patient Selection Criteria

Eligible patients must meet all of the following:

• Minor ischemic stroke with NIHSS ≤3 or high-risk TIA with ABCD² score ≥4 1
• Non-cardioembolic mechanism (no atrial fibrillation or other cardioembolic source) 1
• Presentation within 24 hours of symptom onset (benefit extends to 72 hours but diminishes) 1
• Intracranial hemorrhage ruled out on neuroimaging (CT or MRI) 1
• No contraindications to dual antiplatelet therapy 1

Additional considerations for ticagrelor specifically:

• Patients with symptomatic intracranial or extracranial arterial stenosis ≥30% ipsilateral to the ischemic event derive greater benefit, with stroke or death reduced from 15.2% to 9.9% (HR 0.66,95% CI 0.47–0.93) 2
• In this atherosclerotic subgroup, bleeding events were not significantly higher than aspirin alone 2

Loading Dose Protocol

Administer immediately after eligibility confirmation:

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

Maintenance Dosing (Days 2–30)

Continue for exactly 30 days:

• Ticagrelor: 90 mg twice daily 1
• Aspirin: 75–100 mg once daily 1

The 2021 AHA/ASA guideline specifies that THALES trial data (which used ticagrelor) required loading doses of both agents 2. The maintenance aspirin dose when combined with ticagrelor should be 100 mg once daily per the trial protocol 2.

Transition to Long-Term Therapy (After Day 30)

Discontinue ticagrelor and aspirin dual therapy at exactly 30 days, then switch to single antiplatelet therapy indefinitely:

• First-line: Aspirin 75–100 mg daily 1
• Alternative: Clopidogrel 75 mg daily (for aspirin intolerance) 1
• Alternative: Aspirin 25 mg + extended-release dipyridamole 200 mg twice daily 1

Efficacy and Safety Profile

Efficacy:

• Number needed to treat = 92 to prevent one recurrent stroke at 90 days 1
• Greatest benefit occurs within the first 7 days after stroke 1

Safety:

• Severe bleeding: 0.5% with ticagrelor-aspirin vs 0.1% with aspirin alone 1
• Intracranial hemorrhage: 0.4% with ticagrelor-aspirin vs 0.1% with aspirin alone 1
• Number needed to harm = 263 for severe bleeding 1
• Treatment discontinuation due to bleeding: 2.8% vs 0.6% with aspirin alone 1

Absolute Contraindications

Do NOT use ticagrelor-aspirin in:

• Large strokes (NIHSS >3) 1
• Prior intracranial hemorrhage 1
• Active bleeding or high bleeding risk 1
• Patients requiring intracranial stenting (use aspirin-clopidogrel instead) 1
• History of intracranial hemorrhage (ticagrelor contraindication) 1
• Presentation >72 hours after symptom onset 1
• Recent IV alteplase within 24 hours 1

Comparison to Aspirin-Clopidogrel

Aspirin-clopidogrel is the more established regimen with broader indications:

• Initiated within 12–24 hours and continued for 21 days (up to 90 days acceptable) 1
• Has stronger evidence base than ticagrelor-aspirin 1
• Ticagrelor-aspirin has a narrower indication and must be used for exactly 30 days 1

The choice between clopidogrel and ticagrelor should be based on:

• Patient factors such as medication adherence (cost and dose frequency) 2
• The role of genetic studies or platelet function testing remains unclear 2

Special Populations

Patients with symptomatic intracranial atherosclerotic disease (ICAS):

• Ticagrelor-aspirin may be preferred over clopidogrel-aspirin in this subgroup based on THALES subgroup analysis 2
• In patients with ≥30% intracranial stenosis ipsilateral to the ischemic event, ticagrelor-aspirin reduced stroke/death from 15.2% to 9.9% 2
• Bleeding was not significantly higher in this atherosclerotic subgroup 2

Patients with dysphagia:

• Aspirin 81 mg + ticagrelor can be administered via enteral tube 1
• Aspirin 325 mg rectal suppository is an alternative 1

Critical Timing Considerations

Optimal initiation window:

• Within 12–24 hours of symptom onset yields greatest reduction in recurrent stroke 1
• Acceptable window extends to 72 hours, though efficacy is modestly attenuated 1
• Beyond 72 hours: ticagrelor-aspirin is NOT recommended 1

Common Pitfalls to Avoid

• Never continue ticagrelor-aspirin beyond 30 days in routine stroke prevention, as bleeding risk outweighs benefit 1
• Never use ticagrelor-aspirin as a substitute for thrombolysis or thrombectomy in eligible patients 1
• Never delay initiation beyond 24 hours when eligibility criteria are met 1
• Never use in moderate-to-severe stroke (NIHSS >3) 1

Evidence Quality

The recommendation for ticagrelor-aspirin is based on the THALES trial, which demonstrated efficacy in preventing recurrent stroke in patients with minor stroke or high-risk TIA 2. However, aspirin-clopidogrel has stronger evidence (Class I, Level A) from larger trials (CHANCE and POINT) and remains the preferred dual antiplatelet regimen for most patients 1.