Is ticagrelor (a P2Y12 inhibitor) equivalent to aspirin (acetylsalicylic acid) for the management of transient ischemic attack (TIA)?

Ticagrelor vs Aspirin for Transient Ischemic Attack

Based on the most recent evidence, ticagrelor alone is not superior to aspirin for the prevention of recurrent stroke after transient ischemic attack (TIA), but the combination of ticagrelor plus aspirin is more effective than aspirin alone with an increased bleeding risk.

Efficacy of Ticagrelor Monotherapy vs Aspirin

• The SOCRATES trial directly compared ticagrelor monotherapy to aspirin in patients with acute ischemic stroke or TIA and found that ticagrelor was not superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days 1
• Ticagrelor alone showed a trend toward reduction in ischemic stroke compared to aspirin (5.8% vs 6.7%; hazard ratio 0.87), but this did not reach statistical significance for the primary composite endpoint 1

Efficacy of Ticagrelor Plus Aspirin vs Aspirin Alone

• The THALES trial demonstrated that dual antiplatelet therapy with ticagrelor plus aspirin was more effective than aspirin alone for preventing recurrent stroke within 30 days in patients with mild-to-moderate acute noncardioembolic ischemic stroke or TIA 2
• The combination of ticagrelor plus aspirin reduced the risk of stroke or death within 30 days compared to aspirin alone (5.5% vs 6.6%; hazard ratio 0.83; p=0.02) 2
• Specifically for ischemic stroke, the combination therapy showed greater benefit (5.0% vs 6.3%; hazard ratio 0.79; p=0.004) 2

Safety Considerations

• Severe bleeding was significantly more common with ticagrelor plus aspirin compared to aspirin alone (0.5% vs 0.1%; p=0.001) 2
• Intracranial hemorrhage was also more frequent with ticagrelor plus aspirin versus aspirin alone (0.4% vs 0.1%; p=0.01) 3
• More patients discontinued treatment due to bleeding in the ticagrelor plus aspirin group compared to aspirin alone (2.8% vs 0.6%; p<0.001) 3

Recommendations Based on Current Guidelines

• For patients with TIA, short-term dual antiplatelet therapy with ticagrelor plus aspirin for 30 days may be considered for prevention of recurrent stroke 3
• The recommended dosing regimen is ticagrelor (180-mg loading dose, then 90 mg twice daily) plus aspirin (300- to 325-mg loading dose, then 75–100 mg daily) for 30 days 3
• The number needed to treat to prevent one primary outcome event is 92, while the number needed to harm for severe bleeding is 263 3

Special Considerations for Specific Patient Populations

• In patients with atherosclerosis ipsilateral to the ischemic territory, including intracranial stenosis, the combination of ticagrelor and aspirin showed greater benefit (9.9% vs 15.2% risk of recurrent stroke or death at 30 days; hazard ratio 0.66) 3
• Interestingly, in this subgroup with atherosclerosis, bleeding events were not significantly higher with dual therapy compared to aspirin alone 3
• Caution is warranted in patients with prior stroke or TIA when considering ticagrelor, as these patients have been excluded from some trials due to potential increased risk of intracranial bleeding 3

Practical Algorithm for Management

1. For patients with TIA without contraindications to dual antiplatelet therapy:

   • Consider short-term (30 days) dual antiplatelet therapy with ticagrelor plus aspirin 3, 2
   • Use loading doses of both medications (ticagrelor 180 mg, aspirin 300-325 mg) 3

2. For patients with TIA and ipsilateral atherosclerosis:

   • Dual antiplatelet therapy with ticagrelor plus aspirin may offer greater benefit with potentially less relative bleeding risk 3

3. For long-term therapy after the initial 30 days:

   • Switch to single antiplatelet therapy (either aspirin or clopidogrel) 3
   • There is no evidence supporting long-term ticagrelor monotherapy over aspirin 1

4. For patients with high bleeding risk:

   • Consider aspirin monotherapy instead of dual therapy 3
   • Carefully weigh the modest absolute benefit against the increased bleeding risk 3

Important Caveats

• The benefit of dual antiplatelet therapy is primarily seen in the first 30 days after TIA 2
• Meta-analyses show that P2Y12 inhibitors (including ticagrelor) plus aspirin reduce recurrent stroke risk by 24% compared to aspirin alone, but increase moderate to severe bleeding risk 4
• The choice between ticagrelor and clopidogrel for dual therapy should consider factors like medication adherence, cost, and dosing frequency 3
• The efficacy and safety of ticagrelor in patients with prior stroke or TIA were not well-reported in some trials, making the risk-benefit balance unclear in this population 3