What is the management and treatment for cerebral amyloid angiopathy?

Management and Treatment of Cerebral Amyloid Angiopathy

The cornerstone of CAA management is strict blood pressure control (target systolic BP 130-150 mmHg acutely, <140/90 mmHg long-term) combined with permanent avoidance of all anticoagulation and antiplatelet agents, as these are the only proven interventions to reduce hemorrhage recurrence. 1

Acute Intracerebral Hemorrhage Management

When a patient presents with CAA-related ICH, immediate aggressive interventions are required:

• Target systolic blood pressure to 130-150 mmHg in the acute phase to reduce hematoma expansion and cerebral edema 1
• Initiate BP lowering as soon as CAA-related hemorrhage is identified, without delay 1
• Provide multidisciplinary stroke unit care with early rehabilitation 1
• If the patient is on warfarin, immediately discontinue it and administer 4-factor PCC (25-50 IU/kg based on INR and body weight) without waiting for INR results, plus intravenous vitamin K (5-10 mg) to target INR <1.5 2
• Surgical evacuation has not been shown to improve survival and should only be considered for select cases with life-threatening mass effect threatening herniation 1

Long-Term Blood Pressure Management

Strict BP control is the only proven modifiable intervention to reduce recurrence risk:

• Maintain systolic BP <140/90 mmHg (or <130/80 mmHg if diabetes or chronic kidney disease is present) 1
• This is critical given that recurrence rates are 2.1-3.7% per patient-year, substantially higher in lobar locations 1
• Lobar ICH location is the strongest predictor of recurrence, reflecting underlying CAA 1

Antithrombotic Management: Permanent Avoidance

Anticoagulation and antiplatelet therapy must be permanently avoided in diagnosed CAA due to extremely high risk of recurrent lobar hemorrhage 1:

• A history of lobar ICH suggestive of CAA is sufficient to tip the balance away from anticoagulation in nonvalvular atrial fibrillation 3
• Decision analysis studies demonstrate that elderly patients with lobar hemorrhage likely due to CAA have much higher projected risk of poor outcomes with continuation of warfarin 3
• The risk of recurrent ICH in CAA patients is approximately 7% annually, compared to about 1% for those not fulfilling CAA criteria 3

Key distinction: Deep hemorrhages from hypertensive arteriopathy carry different recurrence risks than lobar hemorrhages from CAA—for patients with small deep ICH, the risk of restarting versus withholding warfarin is similar 3

Alternative Stroke Prevention for Atrial Fibrillation

For CAA patients with atrial fibrillation requiring stroke prevention:

• Left atrial appendage occlusion (LAAC) is the preferred strategy over oral anticoagulation 1, 3
• LAAC reduces ischemic stroke and systemic embolism from AF without exposing patients to long-term bleeding risk from anticoagulation 3
• Calculate CHA₂DS₂-VASc score to assess ischemic stroke risk when making this decision 3

Diagnostic Approach to Guide Management

CAA diagnosis requires validated clinico-radiological criteria before making anticoagulation decisions 1:

• MRI is superior to CT for identifying characteristic features including lobar microbleeds, cortical superficial siderosis, and white matter changes 1
• Multiple juxtacortical microhemorrhages (≥4) <10 mm in diameter on susceptibility-weighted MRI sequences are highly specific for CAA and predict future bleeding risk 3
• Lobar macrohemorrhages >10 mm in diameter significantly increase recurrent hemorrhage risk with anticoagulation 3
• Absence of hypertensive hemorrhage patterns (basal ganglia, thalamus, pons, cerebellum) suggests CAA 1

Additional Risk Factors to Monitor

Beyond BP control and antithrombotic avoidance, recognize these risk factors for recurrence:

• Older age 1
• Apolipoprotein E ε2 or ε4 alleles 1
• Greater number of microbleeds on T2*-weighted gradient-echo MRI 1
• Previous hemorrhage history 1

Current Limitations and Future Directions

No effective therapeutics currently exist to cure or halt CAA progression 1:

• Prevention of hemorrhage through BP control and avoidance of antithrombotics remains the cornerstone of management 1
• Iron chelating agents (deferoxamine) are in early phase trials for oxidative injury after ICH 1
• Anti-amyloid therapies show early promise in animal models but require human testing 1
• Clinical trials are ongoing for NOACs and left atrial appendage occlusion in ICH survivors 1

Critical Pitfalls to Avoid

• Do not rely on CT alone: MRI with gradient-echo or susceptibility-weighted imaging is mandatory to detect microhemorrhages and superficial siderosis that indicate CAA 3
• Do not assume all ICH carries equal recurrence risk: Deep hemorrhages from hypertension have different risk profiles than lobar hemorrhages from CAA 3
• Do not use bleeding risk scores to decide on withdrawing anticoagulation: CAA with lobar ICH or multiple microbleeds represents a specific, validated contraindication that supersedes general bleeding risk assessment 3
• If anticoagulation is ever reconsidered after deep ICH (not lobar): Delay at least 4 weeks and preferably use NOACs over warfarin, though this applies only to non-CAA deep hemorrhages 3