Melbourne, Australia—The use of daily low-dose aspirin significantly increases the likelihood of intracranial bleeding in older adults but does not appear to lessen their risk of ischemic stroke, according to a new study.

The report in the Journal of the American Medical Association Network Open noted a statistically significant 38% increase in intracranial bleeding resulting from a combination of hemorrhagic stroke and other causes of intracerebral hemorrhage among study participants randomized to aspirin. The secondary analysis of a randomized clinical trial included 19,114 older adults.

The researchers from Australian and U.S. universities cautioned, “These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma (e.g., from falls).”

Their results raised questions about whether low-dose aspirin has any role in the primary prevention of stroke, the authors pointed out.

The issue is that low-dose aspirin is widely used for primary and secondary prevention of stroke. “The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals,” according to the report.

The study team sought to establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin (i.e., 100-mg enteric-coated aspirin). They conducted a secondary analysis of Aspirin in Reducing Events in the Elderly (ASPREE)—a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin.

The participants were older adults free of symptomatic cardiovascular disease who lived in the community in Australia or the U.S. Most (56.4%) were female with a median age of 74 years. During the trial, 9,525 participants received aspirin and 9,589 participants received placebo.

The researchers recruited participants between 2010 and 2014 and followed them for a median (interquartile range) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023.

The study assessed outcomes by reviewing medical records; stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on the prevention of an initial stroke or intracranial bleeding event.

Although aspirin was not found to produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR] 0.89; 95% CI, 0.71-1.11), a statistically significant increase in intracranial bleeding was observed among participants assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR 1.38; 95% CI, 1.03-1.84). “This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs. 41 individuals [0.4%]; HR 1.45; 95% CI, 0.98-2.16),” the researchers advised. “Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR 1.33; 95% CI, 0.87-2.04).”

Aspirin, an antiplatelet agent, is widely used in low doses (75-100 mg/day) for the prevention of cardiovascular events, and recent unfavorable findings do not appear to have stemmed its use for primary and secondary prevention of stroke, according to background information in the article.

“Information about the efficacy of low-dose aspirin in the primary prevention of stroke is derived from meta-analyses and results of recent major trials, most of which have been conducted in populations with mean ages younger than 70 years,” the authors wrote. “Despite some inconsistency, these reports suggest a trend toward reduced ischemic stroke counterbalanced by increased intracerebral and other intracranial hemorrhage, with little overall impact on total stroke incidence.”

The study suggested that the situation might be different for older adults because of their increased inherent susceptibility to hemorrhage related to the greater fragility of small blood vessels. Older patients also are more likely to suffer major and minor trauma as a result of falls and other accidents, the study noted. “Together, these outcomes may alter the balance of risks and benefits of an antiplatelet drug, especially if given to individuals at low risk in a primary prevention setting,” the authors explained. “This concern is relevant given the high stroke risk in older individuals, worldwide increases in populations of older individuals, and the importance of evaluating preventive strategies in this age group.”

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