Aspirin Significantly Increases Intracranial Bleeding in Older Individuals

In healthy older patients taking daily low-dose aspirin, there is a significant increase in risk for intracranial bleeding.

In older patients, daily low-dose aspirin results in a small, not statistically significant decrease in ischemic and hemorrhagic strokes and a statistically significant increase in intracranial bleeding, according to findings published in the Journal of the American Medical Association Network Open.

Investigators sought to examine the effect of daily low-dose aspirin on risk for ischemic stroke and intracranial bleeding among healthy older individuals.

They conducted a secondary analysis of a randomized, double-blind, placebo-controlled trial (Aspirin in Reducing Events in the Elderly [ASPREE]) conducted between 2010 and 2014. ASPREE participants were community dwelling older individuals in the US or Australia at least 70 years of age and free of symptomatic cardiovascular disease. Follow-up lasted median 4.7 (IQR, 3.6-5.7) years.

Among 19,114 participants (median age, 74 [IQR, 71.6-77.7] years; 56.4% women; 91.3% White) 9525 individuals were randomly assigned to receive aspirin and 9589 individuals received matching placebo. The primary endpoints were survival, freedom from dementia, and physical disability.

This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke.

Incidence of ischemic stroke was not significantly reduced with aspirin (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). Ischemic stroke occurred in 146 participants receiving aspirin and 166 receiving placebo. The aspirin group had 14 deaths vs 10 deaths in the placebo group.

Incidence of hemorrhagic stroke increased without statistical significance with aspirin (0.5% of participants) vs placebo (0.4%; HR, 1.33; 95% CI, 0.87-2.04). Hemorrhagic stroke occurred in 49 participants receiving aspirin and 37 receiving placebo. The aspirin group had 17 deaths vs 12 deaths in the placebo group.

A statistically significant increase occurred in intracranial bleeding (defined as the combination of hemorrhagic stroke and other causes of intracerebral hemorrhage) among individuals receiving daily aspirin (1.1% of participants) vs placebo (0.8%; HR, 1.38; 95% CI, 1.03-1.84). This increase was the result of the increase in the combination of subdural, extradural, and subarachnoid bleeding with aspirin (0.6% of participants) vs placebo (0.4%; HR, 1.45; 95% CI, 0.98-2.16).

Among individuals receiving 100 mg/daily low-dose aspirin over 5 years (n=1000), the investigators noted that in absolute numbers there were 2.5 fewer ischemic strokes at the expense of 3.5 cases of intracranial hemorrhage, which lacks statistical significance.

Study limitations include the low number of stroke and bleeding events during follow-up and lack of generalizability beyond a White population.

“This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke,” the investigators wrote. “These findings suggest that low-dose aspirin may have no role for the primary prevention of stroke and that caution should be taken with use of aspirin in older persons prone to head trauma.”Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Cloud GC, Williamson JD, Thao LTP, et al. Low-dose aspirin and the risk of stroke and intracerebral bleeding in healthy older people: secondary analysis of a randomized clinical trial. JAMA Netw Open. Published online July 26, 2023. doi:10.1001/jamanetworkopen.2023.25803