Is aspirin (acetyl‑salicylic acid) contraindicated in a patient with cerebral amyloid angiopathy and Alzheimer disease?

Aspirin in Cerebral Amyloid Angiopathy with Alzheimer's Disease

Aspirin is not absolutely contraindicated in patients with CAA and Alzheimer's disease, but a history of lobar intracerebral hemorrhage suggestive of CAA represents a compelling reason to avoid anticoagulation and likely aspirin as well, given the significantly elevated bleeding risk. 1

Key Evidence on Bleeding Risk

The most critical guideline evidence comes from the 2014 AHA/ASA stroke prevention guidelines, which explicitly state that a history of lobar ICH suggestive of cerebral amyloid angiopathy is sufficient to tip the balance away from anticoagulation in nonvalvular atrial fibrillation. 1 While this statement specifically addresses anticoagulation, the principle applies to aspirin given the hemorrhagic risk profile in CAA.

Clinical Trial Data

Two randomized controlled trials directly examined aspirin use in Alzheimer's disease patients:

• In the EVA trial, 4.6% of patients receiving aspirin developed intracerebral hemorrhage (3/65) versus 0% in controls (0/58). 2

• In the AD2000 trial, 2.6% of aspirin-treated patients had ICH (4/156) versus 0% in controls (0/154). 2

• The pooled analysis showed 3.2% ICH rate with aspirin versus 0% without aspirin, with a hazard ratio of 7.63 (95% CI 0.72-81.00, P=0.09). 2

• Importantly, aspirin showed no cognitive benefit in these AD patients, making the risk-benefit calculation even less favorable. 2

Decision Algorithm for Aspirin Use

When Aspirin Should Be Avoided:

• History of lobar intracerebral hemorrhage 1
• Active gastrointestinal bleeding or recent GI hemorrhage 3, 4
• Documented aspirin allergy or hypersensitivity 3, 4, 5
• Severe thrombocytopenia 4
• Multiple cortical microhemorrhages or cortical superficial siderosis on MRI (these are CAA-associated hemorrhagic markers) 6

When Aspirin May Be Considered Despite CAA:

• Compelling cardiovascular indication (e.g., recent MI, unstable angina, acute coronary syndrome) - the AHA guidelines state aspirin should not be withheld if there is an unequivocal cardiovascular indication 1, 2

• High atherosclerotic cardiovascular disease risk (≥10% 10-year risk) without prior ICH - use lowest effective dose of 75-100 mg daily 4, 5

• CAC score ≥100 without hemorrhagic complications - this identifies patients where cardiovascular benefit may exceed bleeding risk 1, 4

Practical Management Approach

If aspirin is deemed necessary for cardiovascular indications:

• Use the lowest effective dose: 75-100 mg daily (or 81 mg in US formulations) 3, 4, 5
• Higher doses (≥160 mg) increase bleeding risk without improving cardiovascular outcomes 3
• Add a proton pump inhibitor to reduce GI bleeding risk 4
• Obtain baseline brain MRI with gradient-echo T2 or susceptibility-weighted imaging to detect microhemorrhages and cortical superficial siderosis* 6
• Avoid combining with NSAIDs, which significantly increase bleeding risk and cardiovascular events 3, 5

If aspirin must be avoided but antiplatelet therapy is needed:

• Clopidogrel 75 mg daily is the recommended alternative 1, 4, 5
• However, clopidogrel also carries bleeding risk in CAA patients, so the same hemorrhagic risk assessment applies

Critical Pathophysiology Context

CAA is present in over 90% of Alzheimer's disease patients and involves amyloid-β deposition in cerebral vessel walls, which weakens vessel structure and predisposes to both hemorrhage and infarction. 7, 8 The occipital lobe is most commonly affected. 7

Animal studies showed that low-dose aspirin did not increase hemorrhagic lesions in CAA mice models, but this reassuring preclinical finding contrasts with the human trial data showing increased ICH risk. 9

Bottom Line

For a patient with known CAA and Alzheimer's disease without prior lobar hemorrhage and without compelling cardiovascular indication, aspirin should be avoided given the 3.2% ICH risk and lack of cognitive benefit. 2 If there is an unequivocal cardiovascular indication (acute coronary syndrome, recent MI, high-risk unstable angina), aspirin should not be withheld, but use the lowest dose (75-100 mg daily) with PPI gastroprotection and close monitoring. 1, 3, 4, 2