Pooled results of two small trials with few events show a non-significant trend towards increased risk of intracerebral haemorrhage in people with Alzheimer's disease
- Correspondence to Barbara E Harrison
464 O’Dowd Hall, Oakland University, Rochester, Michigan 48309, USA;
Alzheimer's disease and aspirin use
Alzheimer's disease (AD) is a neurodegenerative brain disease that leads to dementia. It is often accompanied by small vessel disease because of arteriosclerosis.1 AD and atherothrombosis share some common pathogenetic mechanisms which include chronic inflammation.2 Although the exact mechanism underlying this effect is still unknown, some have suggested aspirin use for patients with AD because of its anti-inflammatory properties.3 Thus aspirin use in AD has been considered by some researchers as a potential therapy for delaying the progression of AD through slowing of the neuroinflammatory response.4
Thoonsen and colleagues did a systematic review of PubMed and the Cochrane Library in October 2009 for studies that investigated the effect of aspirin use in AD patients. They compared the occurrence of intracerebral haemorrhage (ICH) over time between low-dose aspirin users and control groups using Cox regression. However, only two randomised controlled trials (RCTs) on aspirin use in AD patients were located: the Evaluation of Vascular Care in Alzheimer's Disease (EVA) trial (conducted in their research centre) and the Aspirin in Alzheimer's Disease (AD2000) trial.
The total number of ICH events in both samples was seven patients in a pooled sample of 433 with end points of 22 and 29 months. The pooled proportion of ICHs in the aspirin group was 3.2% (7/221, 95% confidence interval (CI) 1.3% to 6.4%) versus 0% in the control group (0/212, 95% CI 0% to 1.7%). The pooled HR for an ICH in AD patients using aspirin was 7.63 (95% CI 0.72 to 81.00, p=0.09). Thus their results did not reach statistical significance, and the CI is wide. The authors' conclusion was that although the number of cases in both trials was small, the findings suggest that aspirin use in AD might pose an increased risk of ICH.
The evidence linking low dose aspirin use and ICH in patients with AD is not sufficient yet to change practice. This study's major limitation is the limited sample size, and the authors acknowledge that the increase in ICH was not statistically significant. Replication with a larger sample and measurement over a longer time period may provide researchers with adequate methods to more clearly determine the evidence for the risk of ICH in AD patients using low-dose aspirin. They conclude, “aspirin should not be prescribed for AD patients to slow cognitive decline if no clear cardiovascular indication exists.”
If the evidence for an increased risk of ICH among patients with AD using small doses of aspirin is found, then these results have important implications for nursing practice and research. Nurses and advanced practice nurses often advise or prescribe aspirin to patients diagnosed with dementia based on the neuro-inflammatory theory. If the increased risk for ICH is substantiated by evidence from future RCTs, then nurses need to advise AD patients about the risk for ICH associated with lose-dose aspirin use. Aspirin use is often assumed to be without risk at low doses in otherwise healthy patients. This assumption about safety in AD patients is now challenged by these results, but more research is needed to confirm this.
Although it is important that more high-quality RCTs are undertaken which examine the risk of low-dose aspirin use with AD patients, the finding supports at least one other study4 which found that pre-existing dementia is frequent in patients with ICH and may be the consequence of neurodegeneration and cerebral amyloid angiopathy.5 If AD patients are at risk for ICH because of amyloid angiopathy, then low-dose aspirin use (due to its influence on platelets) could contribute to ICH.