What is the role of anticoagulation in cerebral amyloid angiopathy?

From the Guidelines

Anticoagulation in cerebral amyloid angiopathy (CAA) is generally contraindicated due to the significantly increased risk of intracranial hemorrhage, and patients with CAA should avoid all anticoagulants and antiplatelet agents whenever possible. The pathophysiology of CAA, which involves amyloid protein deposition in cerebral blood vessel walls, making them fragile and prone to rupture, combined with the bleeding risk from anticoagulants, creates a particularly dangerous combination that can lead to life-threatening cerebral hemorrhages 1.

Key Considerations

• Patients with CAA should avoid all anticoagulants (including warfarin, direct oral anticoagulants like apixaban and rivaroxaban) and antiplatelet agents (such as aspirin, clopidogrel) whenever possible.
• If a patient with CAA has a compelling indication for anticoagulation, such as atrial fibrillation with high stroke risk, the decision requires careful individualized risk-benefit assessment, considering the potential benefits of anticoagulation against the increased risk of intracranial hemorrhage 1.
• In such cases, left atrial appendage closure might be considered as an alternative to pharmacological anticoagulation.
• For patients who absolutely require some form of antithrombotic therapy, using the lowest effective dose of a single antiplatelet agent may be the safest compromise.

Monitoring and Management

• Regular monitoring for microbleeds using MRI with susceptibility-weighted imaging may help guide management decisions in these challenging cases.
• The selection of the antithrombotic agent should be based upon the absolute risks of stroke and bleeding and the relative risk and benefit for a given patient, as recommended by guidelines for the management of patients with atrial fibrillation 1.

Guideline Recommendations

• Guidelines recommend antithrombotic therapy to prevent thromboembolism for all patients with AF, except those with lone AF or contraindications, but these guidelines do not specifically address the risks associated with CAA 1.
• The need for anticoagulation should be re-evaluated at regular intervals, taking into account the patient's changing risk profile and any new evidence regarding the safety and efficacy of anticoagulation in patients with CAA.

From the Research

Anticoagulation in Cerebral Amyloid Angiopathy

• The use of anticoagulation in patients with cerebral amyloid angiopathy (CAA) and atrial fibrillation (AF) is a complex issue, as it requires balancing the risk of ischemic stroke against the risk of intracranial hemorrhage 2, 3, 4, 5, 6.
• CAA increases the risk of intracranial hemorrhage, and the presence of CAA biomarkers such as cortical microbleeds (CMBs), cortical superficial siderosis (cSS), convexal subarachnoid hemorrhage (cSAH), and lobar intracerebral hemorrhage (ICH) can help quantify this risk 2, 3, 5.
• The risk of ischemic stroke in AF can be quantified using the CHA2DS2-VASc score, and patients deemed not low risk should be anticoagulated 2.
• However, in patients with CAA, antithrombotics should be avoided in those with predominant ICH, cSS, or cSAH features, and those with ≥2 CMBs require in-depth risk-benefit analysis using a multidisciplinary approach 2, 5.
• Direct oral anticoagulants (DOACs) may be preferred over vitamin K antagonists (VKAs) due to a lower risk of intracranial hemorrhage 5.
• Close clinical and radiological monitoring is essential in patients with CAA who are anticoagulated, and left atrial appendage occlusion may be considered in those who are not anticoagulated 5.
• A balanced approach is necessary when making anticoagulation decisions in patients with CAA, taking into account the individual patient's risk factors and clinical presentation 6.