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HomeA Practitioner's Must ReadBrain bleed risk upped by daily aspirin – second ASPREE trial analysis

Brain bleed risk upped by daily aspirin – second ASPREE trial analysis

Taking a low, daily dose of aspirin will not prevent the most common type of stroke among older people who have never had one before, and in fact, may actually increase their risk of a dangerous brain bleed, according to medical experts, who found that it also increases the risks of falls in elderly people.

“This is just more evidence that prescribing aspirin to someone who doesn’t need it is not a great idea,” said John McNeil at Monash University in Melbourne, Australia.

As people age, they have an increasing chance of developing blood clots, which could block blood flow to the brain and trigger as an ischaemic stroke. New Scientist reports that attempting to counter that risk, doctors sometimes prescribe them 75mg to 100mg of aspirin – generally considered to be a low dose – to take every day, as the drug thins the blood.

But aspirin, even at low doses, doesn’t come without risks, said McNeil last November, when he and his colleagues showed that a daily low dose of aspirin increases the risks of falls in older people.

As part of the same trial, McNeil and his team investigated strokes and internal head bleeds in 19 114 people over an average of nearly five years. Of these participants, 17 725 were at least 70-years-old and living in Australia, and the vast majority were white. The remaining 1 389 participants were Hispanic or African American adults aged 65 and older, living in the US.

None had a history of a stroke or any other cardiovascular condition at the start of the study.

Roughly half were assigned to take 100mg of aspirin every day, while the other half took a placebo pill.

Among those taking low-dose aspirin, 1.5% experienced an ischaemic stroke during the study period, compared with 1.7% in the placebo group. Taking into consideration the number of years each person was involved in the study, the researchers found aspirin didn’t reduce their risk of an ischaemic stroke. This remained true when they broke down the categories of participants according to their age, sex and race or ethnicity.

When it comes to aspirin’s side effects, 1.1% of the participants who took it experienced bleeding inside or around their brain, compared with only 0.8% of those taking a placebo.

While this may sound like a small difference, a statistical analysis suggests it wasn’t a chance finding. These bleeds sometimes occurred after a blow to the head, like during a fall, but were sometimes spontaneous.

This finding is especially important because intracranial bleeding is usually more fatal than an ischaemic stroke, said McNeil. As well as aspirin’s blood-thinning properties, people’s blood vessels naturally weaken with age, making them more likely to cause a haemorrhage, he says.

The results only apply to people with no history of a cardiovascular condition, however. Low-dose aspirin may help to cut the risk of strokes in people with these conditions, he said.

Study details

Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People: Secondary Analysis of a Randomised Clinical Trial

Geoffrey Cloud,  Jeff Williamson,  John McNeil, et al.

Published in JAMA Network Open on 26 July 2023

Key Points

Question In a primary prevention setting, does long-term, daily low-dose aspirin treatment affect the incidence of stroke or intracerebral bleeding?
Findings This secondary analysis of a randomised clinical trial including 19 114 older adults found a statistically significant 38% increase in intracranial bleeding resulting from a combination of haemorrhagic stroke and other causes of intracerebral haemorrhage among individuals randomised to aspirin. The difference in incidence of ischaemic stroke was not statistically significant.
Meaning 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 (eg, from falls).

Abstract

Importance
Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischaemic stroke events and increased intracranial bleeding has not been established in older individuals.

Objective
To establish the risks of ischaemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin.

Design, Setting, and Participants
This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomised, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023.

Interventions
Daily 100-mg enteric-coated aspirin or matching placebo.

Main Outcomes and Measures
Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records.

Results
Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9 525 individuals received aspirin and 9 589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischaemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals 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). Haemorrhagic 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).

Conclusions and Relevance
This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischaemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma.

 

JAMA Network Open article – Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People (Creative Commons Licence)

 

New Scientist article – Aspirin raises the risk of brain bleeds and may not prevent strokes (Open access)

 

See more from MedicalBrief archives:

 

Regular aspirin increases anaemia risk in seniors – ASPREE study

 

Daily aspirin increases risk of falls in the elderly – ASPREE trial

 

Aspirin reduces cardiovascular events in elderly with raised Lp(a) – ASPREE analysis

 

Aspirin reduces cardiovascular events in elderly with raised Lp(a) – ASPREE analysis

 

 

 

 

 

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