Can I use a combination of aspirin and ticagrelor (P2Y12 inhibitor) for 90 days for Intracranial Atherosclerotic Disease (ICAD)?

Using Aspirin and Ticagrelor Combination for Intracranial Atherosclerotic Disease (ICAD)

Yes, the combination of aspirin and ticagrelor for 90 days can be used for Intracranial Atherosclerotic Disease (ICAD), particularly in patients with recent stroke or TIA attributable to severe stenosis (70-99%) of a major intracranial artery.

Evidence for Dual Antiplatelet Therapy in ICAD

The 2021 AHA/ASA guidelines provide specific recommendations for antiplatelet therapy in ICAD:

• For patients with recent stroke or TIA (within 30 days) attributable to severe stenosis (70%-99%) of a major intracranial artery, adding clopidogrel 75 mg/day to aspirin for up to 90 days is reasonable to reduce recurrent stroke risk (Class 2a, Level B-NR) 1

• For patients with recent (within 24 hours) minor stroke or high-risk TIA and concomitant ipsilateral >30% stenosis of a major intracranial artery, adding ticagrelor 90 mg twice daily to aspirin for up to 30 days might be considered (Class 2b, Level B-NR) 1

Ticagrelor vs. Clopidogrel in ICAD

The THALES trial subgroup analysis showed that patients with ≥30% intracranial stenosis ipsilateral to the ischemic event had a lower risk of recurrent stroke or death at 30 days with ticagrelor 90 mg twice daily plus aspirin 100 mg once daily compared to aspirin alone (9.9% vs 15.2%; HR 0.66; 95% CI 0.47-0.93; P=0.016) 1.

Importantly, unlike in patients without atherosclerosis, bleeding events were not significantly higher in the ipsilateral atherosclerosis subgroup treated with ticagrelor and aspirin compared to aspirin alone 1.

Duration of Therapy

• The standard recommendation for dual antiplatelet therapy duration in ICAD is up to 90 days
• After 90 days, transition to single antiplatelet therapy is recommended to minimize bleeding risk

Treatment Algorithm for ICAD

1. Initial Assessment:

   • Confirm ICAD diagnosis with appropriate imaging
   • Determine degree of stenosis (mild 30-49%, moderate 50-69%, severe 70-99%)
   • Assess time since stroke/TIA event

2. Treatment Selection:

   • For severe stenosis (70-99%):

     • Aspirin 100mg daily + ticagrelor 90mg twice daily for 90 days
     • Loading doses: ticagrelor 180mg, aspirin 300mg

   • For moderate stenosis (50-69%):

     • Consider dual antiplatelet therapy, but benefits less established
     • Aspirin monotherapy is an alternative

3. After 90 Days:

   • Transition to single antiplatelet therapy (aspirin or clopidogrel)
   • Continue indefinitely with risk factor management

Important Considerations

• CYP2C19 Genetic Status: Ticagrelor may be particularly beneficial in patients who are CYP2C19 loss-of-function allele carriers, as its effectiveness is not affected by this genetic variant 2

• Bleeding Risk: Monitor for bleeding complications throughout the treatment period

• Comprehensive Management: Dual antiplatelet therapy should be part of a comprehensive approach that includes:

  • Blood pressure control (target SBP <140 mmHg)
  • High-intensity statin therapy
  • Moderate physical activity 1

Potential Pitfalls

1. Premature Discontinuation: Stopping dual antiplatelet therapy too early increases recurrent stroke risk, particularly in the first 30 days when risk is highest

2. Extended Duration Beyond Recommendation: Continuing dual therapy beyond 90 days increases bleeding risk without clear additional benefit

3. Medication Interactions: Be aware of drugs that may interact with ticagrelor (e.g., strong CYP3A4 inhibitors/inducers)

4. Compliance Issues: Twice-daily dosing of ticagrelor may affect adherence compared to once-daily clopidogrel

In summary, using the combination of aspirin and ticagrelor for 90 days in ICAD is supported by clinical evidence, particularly for patients with severe stenosis or those who are CYP2C19 loss-of-function allele carriers. This approach should be implemented as part of comprehensive stroke risk management.