What is the long-term risk of intracerebral hemorrhage in patients with cerebral amyloid angiopathy on antiplatelet (antiplatelet therapy) versus anticoagulation (anticoagulant therapy)?

Risk of Intracerebral Hemorrhage in Cerebral Amyloid Angiopathy: Antiplatelet vs. Anticoagulation Therapy

Patients with cerebral amyloid angiopathy (CAA) should avoid anticoagulation therapy due to significantly higher risk of intracerebral hemorrhage compared to antiplatelet therapy, and left atrial appendage closure should be considered as a preferred alternative when stroke prevention is required. 1

Risk Assessment in CAA Patients

Hemorrhage Risk Factors

• Location of hemorrhage: Lobar ICH location is the most consistently identified risk factor for recurrent ICH, with an annual recurrence rate of approximately 7% for CAA-related hemorrhages compared to about 1% for non-CAA hemorrhages 2
• Imaging biomarkers:
  • Cerebral microbleeds (CMBs) on T2*-weighted gradient-echo MRI indicate higher recurrence risk 2
  • Cortical superficial siderosis and convexal subarachnoid hemorrhage are associated with even higher ICH risk (up to 19% annually) 3
• Genetic factors: Apolipoprotein E ε2 or ε4 alleles increase recurrence risk 2

Comparative Risk with Antithrombotics

Anticoagulation Therapy

• Oral anticoagulation is associated with:
  • Worse ICH outcomes 2
  • Increased risk of ICH recurrence 2
  • Vitamin K antagonists (e.g., warfarin) increase ICH risk twofold compared to direct oral anticoagulants 1

Antiplatelet Therapy

• Effects on ICH recurrence and severity appear "substantially smaller than for anticoagulation" 2
• Antiplatelet therapy carries an odds ratio of 1.7 for microhemorrhages compared to 2.7 for vitamin K antagonists 4
• Antiplatelet agents may be a safer alternative to anticoagulation following ICH 2

Management Recommendations

For Patients Requiring Stroke Prevention

1. First-line approach: Left atrial appendage closure (LAAC) is recommended as the safest option for CAA patients who need stroke prevention (particularly those with atrial fibrillation) 1, 5

   • LAAC appears safe and tolerable in CAA patients 5
   • Avoids long-term antithrombotic therapy

2. If antithrombotic therapy is necessary:

   • Prefer direct oral anticoagulants over warfarin if anticoagulation is required 1
   • Consider antiplatelet therapy as a safer alternative to anticoagulation 2
   • Avoid combined anticoagulant and antiplatelet therapy, which further increases hemorrhage risk 1

Risk Mitigation Strategies

• Blood pressure control: Strict treatment of hypertension can lower ICH risk in persons with probable CAA by 77% 4
• Avoid statins after lobar ICH: Statin use after lobar ICH increases risk of recurrent hemorrhage from 14% to 22% 4
• Avoid alcohol: Frequent alcohol use has been linked to increased ICH risk 2

Special Considerations

• For patients with high CHA₂DS₂-VASc scores but also high CAA-related hemorrhage risk, a multidisciplinary approach is essential to weigh ischemic versus hemorrhagic risks 3
• In patients with CAA and prior lobar ICH, anticoagulation is likely to shorten quality-adjusted survival due to the high risk of recurrence 2
• If temporary cessation of anticoagulation is needed after ICH, 10-15 days without anticoagulation carries a relatively low risk of ischemic events 1

In conclusion, the long-term risk of intracerebral hemorrhage is substantially higher with anticoagulation than with antiplatelet therapy in patients with CAA. When stroke prevention is required, LAAC should be considered as the preferred approach to avoid long-term antithrombotic therapy altogether.