Does long-term, daily low-dose aspirin treatment affect the incidence of stroke or intracerebral bleeding?

In a recent study published in the JAMA Network Open Journal, researchers found that older adults who took aspirin had a 38% higher risk of intracranial bleeding from hemorrhagic stroke and other causes of intracerebral hemorrhage.

The study suggested that low-dose aspirin may not be primary stroke prevention and advised caution.

Study: Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People. Image Credit: fizkes/


Aspirin is a blood-thinning agent often used in low doses (75–100 mg/d) to avoid heart attacks and strokes. Meta-analyses and significant studies have previously supported the effectiveness of low-dose aspirin in preventing strokes.

These studies have primarily focused on groups with an average age of below 70. However, older individuals have unique clinical characteristics that may affect the risks and benefits of aspirin therapy.

Older adults are more susceptible to hemorrhage due to the fragility of small blood vessels and are more prone to falls and accidents.

In the present study, the aspirin in reducing events in the elderly (ASPREE) trial aims to address these concerns and investigate the risks and benefits of low-dose aspirin in older age groups.

About the study

ASPREE is a prospective, randomized, placebo-controlled trial of daily low-dose aspirin in community-dwelling, cardiovascular disease-free older adults. The trial was hosted by Australia and the US between March 2010 to December 2014.

The study participants had no previous atrial fibrillation, stroke, acute ischemic attack, or heart attack record. The study comprised US racial or ethnic minority 65-70-year-olds at risk of cardiovascular disease.

The participants were randomly allocated to receive 100 mg of enteric-coated aspirin or a placebo. The primary endpoint of the ASPREE study, disability-free survival, was not significantly different between the aspirin and placebo groups.

At least two members of an expert committee independently judged suspected stroke and hemorrhagic episodes, which were secondary outcomes. The patient's usual hospital treatment data supported judgments, including brain and vascular imaging and cardiological testing.

This analysis used December 2019 ASPREE data collection version 3. Intention-to-treat analyses examined the effects of aspirin on time to first ischemic stroke, intracranial bleeding, and intracranial bleeding subtypes using Cox proportional hazards regression models.

Frequency and % were descriptive statistics. Cause-specific hazards and cumulative incidence estimates accounted for competing risks.

In ischemic stroke and first intracranial hemorrhage, the treatment effect was assessed across age, sex, smoking history, hypertension and diabetes, lipid disorders, frailty category, and countries (Australia and the US).

The median survival time of aspirin or placebo patients determined the number needed to treat. Analyses were performed using R 4.0 version and a two-sided P value of 0.05 as the statistical significance threshold.


A 2010-2014 trial of 19,114 Australian and US volunteers found that aspirin and placebo effectively prevented ischemic strokes in elderly primary prevention patients. Intracranial events, including stroke, were modest at 5.8 per 1,000 person-years of follow-up.

However, 31 aspirin-induced strokes and 22 placebo-induced strokes led to the death of 53 people, and aspirin users had 91 cardiovascular disease fatalities compared to 112 placebo users.

ASPREE, the first randomized clinical trial to examine aspirin's risks and benefits in elderly primary prevention patients, found more intracerebral hemorrhagic episodes than ischemic strokes.

The study is based on an older, healthy group with no history of cardiovascular or cerebrovascular disease, and the lack of an effect on ischemic stroke is surprising.

Aspirin and placebo-treated groups differed most in small vessel blockage and cardioembolic strokes, with identical ischemic strokes from big arteries.

An early placebo-controlled aspirin experiment showed no impact even after two years. The current investigation found that random aspirin treatment increased intracerebral, subdural, and extradural bleeding, with lobar areas having more cases than basal ganglia.

Over 21% of strokes had intracerebral hemorrhage, but one-third was fatal, compared to 7.7% of ischemic strokes.

Aspirin and placebo patients with subdural hematomas and subarachnoid hemorrhages had equal mortality rates. The risk-benefit trade-off in younger populations may have been neglected, as ischemic strokes declined faster than hemorrhagic occurrences.

Strengths, limitations, and conclusions

The study's strengths include its scope, follow-up, and expert physicians' comprehensive assessment of stroke occurrences. However, it has limitations, including fewer stroke and bleeding incidents and a lack of thorough inquiry.

The findings apply to the White population with routine cholesterol and blood pressure management.

In conclusion, the findings suggest that the randomized clinical trial did not demonstrate a significant reduction in the incidence of cerebral hemorrhage due to aspirin use, supporting the US Preventive Services Task Force (USPSTF) recommendation against the use of low-dose aspirin for primary stroke prevention in healthy elderly individuals.

Journal reference:
  • Cloud, G. et al. (2023) "Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People", JAMA Network Open, 6(7), p. e2325803. doi: 10.1001/jamanetworkopen.2023.25803.

Posted in: Medical Science News | Medical Research News | Medical Condition News | Healthcare News

Tags: Aspirin, Atrial Fibrillation, Bleeding, Blood, Blood Pressure, Blood Vessels, Brain, Cardiovascular Disease, Cerebrovascular Disease, Cholesterol, Clinical Trial, Diabetes, Disability, Frequency, Heart, Heart Attack, Hospital, Imaging, Intracerebral Hemorrhage, Ischemic Stroke, Mortality, Placebo, Smoking, Stroke, Vascular

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Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.