What is the optimal management of cerebral amyloid angiopathy in elderly patients, including anticoagulation avoidance, antiplatelet use, blood pressure control, and treatment of acute lobar hemorrhage?

Management of Cerebral Amyloid Angiopathy

In patients with cerebral amyloid angiopathy (CAA), anticoagulation should generally be avoided, particularly after lobar intracerebral hemorrhage, due to the very high risk of recurrent intracranial hemorrhage that generally precludes anticoagulation use. 1

Anticoagulation Management

Avoidance in CAA Patients

• Anticoagulation is contraindicated in patients with a diagnosis of CAA and symptomatic lobar ICH due to the very high risk of recurrent intracranial hemorrhage. 1
• A history of lobar ICH suggestive of cerebral amyloid angiopathy is sufficient to tip the balance away from anticoagulation in nonvalvular atrial fibrillation. 1
• Decision analysis studies recommend against restarting anticoagulation in patients with lobar ICH and atrial fibrillation. 1

Special Considerations for Atrial Fibrillation

• For elderly patients with lobar hemorrhage likely due to amyloid angiopathy, there is a much higher projected risk of poor outcome with continuation of warfarin compared to patients with deep ICH. 1
• In patients with lower risk of cerebral infarction (e.g., AF without prior ischemic stroke) and higher risk of amyloid angiopathy (elderly patient with lobar ICH, particularly with microbleeds on MRI), antiplatelet agents may be a better choice than warfarin. 1
• Left atrial appendage occlusion can be considered where the risk of anticoagulation seems prohibitive in patients with atrial fibrillation and CAA. 2

Antiplatelet Therapy

Evidence for Use

• The RESTART trial demonstrated that starting antiplatelet treatment after ICH was unlikely to increase the risk of recurrent ICH (adjusted hazard ratio 0.51,95% CI 0.25-1.03) and may actually decrease recurrence risk. 1
• In patients presenting with ICH while taking antiplatelets, restarting treatment appeared to reduce recurrent ICH and improve outcomes. 2

Risk Stratification

• The risk/benefit ratio evaluation at individual level of antiplatelet agents is required in CAA patients. 3
• In patients with a microbleed-only phenotype, the risk of ischemic stroke exceeds the risk of ICH at all cerebral microbleed burdens, supporting antiplatelet use. 2
• Caution should be exercised in prescribing platelet aggregation inhibitors for patients with CAA, particularly those with cortical superficial siderosis or cortical subarachnoid hemorrhage. 4, 5

Blood Pressure Control

Target Blood Pressure

• ICH patients should have their blood pressure lowered to <130 mm Hg systolic and 80 mm Hg diastolic, particularly in the presence of diabetes mellitus, heart failure, or chronic kidney disease. 1
• Strict treatment of arterial hypertension can lower the risk of ICH in persons with probable CAA by 77%. 5

Evidence Base

• In the PROGRESS trial, treatment with perindopril (4 mg daily) and indapamide reduced baseline BP by an average of 12 mm Hg systolic and 5 mm Hg diastolic and lowered the risks of first and recurrent ICH (adjusted HR 0.44,95% CI 0.28-0.69). 1
• The lowest risk of stroke recurrence was seen among patients with the lowest follow-up BP levels (median 112 mm Hg systolic and 72 mm Hg diastolic). 1
• The SPS3 study showed that lowering target SBP to <130 mm Hg significantly reduced the risk of ICH by 60% (HR 0.37, P=0.03). 1

Additional Considerations

• BP variability, presence of obstructive sleep apnea, obesity, and other lifestyle modifications should be addressed despite lack of systematic data regarding their effect on ICH recurrence. 1
• Frequent alcohol use (>2 drinks per day) and illicit drug use should be avoided as they are linked to elevated BP and ICH. 1

Acute Lobar Hemorrhage Management

Prognostication and Care Intensity

• Aggressive care early after ICH onset and postponement of new DNAR orders until at least the second full day of hospitalization is recommended (Class IIa, Level of Evidence B). 1
• Current prognostic models for individual patients early after ICH are biased by failure to account for the influence of withdrawal of support and early DNAR orders. 1
• DNAR status should not limit appropriate medical and surgical interventions unless otherwise explicitly indicated. 1

Risk Factors for Recurrence

• CAA is a recognized risk factor for recurrent ICH, particularly in lobar locations. 1
• Carriers of the apolipoprotein E ε2 or ε4 alleles and patients with a greater number of microbleeds (particularly in lobar brain locations) on gradient echo MRI are at higher risk for ICH recurrence. 1
• The cumulative risk of ICH recurrence is 1% to 5% per year, with the highest risk in the first year after the initial event. 1

Common Pitfalls

• Do not restart anticoagulation in elderly patients with lobar ICH, as this population has the highest prevalence of CAA and greatest risk of recurrent hemorrhage. 1
• Avoid using statins after a lobar ICH, as they increase the risk for clinically manifest recurrent hemorrhage from 14% to 22%. 5
• Do not assume that microbleeds on MRI are an absolute contraindication to antiplatelet therapy; the clinical context and microbleed burden must be considered. 2
• Recognize that cortical superficial siderosis and cortical subarachnoid hemorrhage are important imaging predictors for recurrent ICH and should influence antithrombotic decisions. 4