July 26, 2023

expert reaction to study looking at low-dose aspirin and the risk of stroke and intracerebral bleeding in healthy older people

A study published in JAMA Network Open looked at low-dose aspirin, stroke prevention and bleeding risk.

Prof Stephen Evans, Emeritus Professor of Pharmacoepidemiology, The London School of Hygiene and Tropical Medicine, said:

“This paper follows on from the previously reported results of the ASPREE trial, for which the main results on cardiovascular events (fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure) and bleeding were published in 2018.  Despite a small possible reduction in the cardiovascular events of 6 events per 10,000 person years, there was no overall benefit and a definite increase of major bleeding by 24 events per 10,000 person years.

“This new paper concentrates on the bleeding risks in the trial participants.

“Low-dose aspirin is primarily given for prevention of Coronary Heart Disease.  This trial only included those “free of overt cardiovascular disease”, and excluded those who were likely to benefit from low-dose aspirin.

“This trial found only a small (5 per 10,000 person years) reduction in strokes that night be prevented by aspirin (ischaemic strokes), but an increase in “All intracranial bleeding, including hemorrhagic stroke” of 7 per 10,000 person years.

“For all medicines, and especially those having effects around cardiovascular disease, it is always a balance of risk and benefit.  Low-dose aspirin has a benefit of reducing some forms of clotting and therefore reducing heart attacks but increases risks of bleeding.  A drug which helps prevent bleeding (e.g. aprotinin [https://en.wikipedia.org/wiki/Aprotinin] will increase risks of clotting.

“Therefore, it is important that the right balance is struck in any individual patient.

“What should be emphasised is not any overall harm of low-dose aspirin, but lack of an overall benefit in this group with no overt cardiovascular risk.”

Prof Craig Anderson, Director, Global Brain Health, The George Institute for Global Health, said:

“This paper reports secondary analysis of the pivotal US-Australian ASPREE clinical trial that assessed the balance of potential benefits and risks of low-dose aspirin for the primary prevention of cardiovascular disease in nearly 20,000 older people (age ≥70 years) conducted between 2010 and 2014.  Given that rates of serious cardiovascular events such as stroke and heart attack increase with age, this trial was very important in determining whether aspirin could prevent this from occurring in otherwise well older people.  The trial showed no overall net benefit of aspirin, nor on the specific endpoints of cardiovascular disease or cancer.

“This further analysis re-emphasises that fact that aspirin, widely used and proven for preventing recurrent heart attacks and stroke, has a clear increase in risk of major haemorrhage in the skull and brain.  However, this risk is tiny; an increase of 1:1000 people treated per year.  Even so, this harm will offset any small perceived benefit that aspirin might provide in terms of preventing heart attacks and stroke over the long term.  For aspirin to offer benefit, the individual’s risk of serious cardiovascular disease event should be at least 1% per year.”

Prof Cathie Sudlow, Chief Scientist and Deputy Director, Health Data Research UK; and Director, BHF Data Science Centre, said:

“This isn’t a fundamentally new finding and is consistent with previous studies and overviews/meta-analyses of aspirin in primary prevention of vascular events e.g. see https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791538 and https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60503-1/fulltext

“It is always problematic to rely overly heavily on results from one trial, especially where the focus is on one outcome (stroke) rather than a spectrum of outcomes (all vascular events) – far more reliable will be systematic overviews of all the relevant evidence.

“Aspirin is not currently recommended for primary prevention in older people so this is not a policy changing finding.”

Dr Richard Francis, Head of Research, Stroke Association said: 

“There are two main types of stroke, those caused by a clot (ischaemic) and those caused by a bleed on/in the brain (haemorrhagic).  In the UK, people who have previously had an ischaemic stroke or heart attack may be prescribed daily low-dose aspirin to reduce their risk of another.  This study looked at the use of aspirin to prevent first-time ischaemic stroke.

“Evidence indicates that daily low-dose aspirin does not lower first-time stroke risk and its use also has potential harmful side effects, including increased risk of brain bleeds, which are deadly in many cases.  This study adds weight to the evidence that current recommendations are correct and that aspirin should not be used to prevent ischaemic stroke or heart attacks in people with no previous history of stroke or heart attack.  It also, for the first time, makes clear that the recommendation against aspirin for primary prevention of ischaemic strokes and heart attacks remains applicable for people aged 70 or over, which is important as the risk of stroke increases with age.

“The findings from this study do not suggest that the use of daily low-dose aspirin to reduce risk of recurrent ischaemic strokes or heart attacks should change.  However, the decision to prescribe daily low-dose aspirin for secondary prevention needs to be made on an individual basis, balancing the risks related to stroke and heart attack with the risks of side effects.  If, however, you are taking low-dose aspirin for secondary prevention of ischaemic stroke and/or heart attack and are concerned by these findings, you should talk to your GP.”

‘Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People: Secondary Analysis of a Randomized Clinical Trial’ by Geoffrey C. Cloud et al. was published in JAMA Network Open at 16:00 UK time on Wednesday 26 July 2023.

DOI: https://doi.org/10.1001/jamanetworkopen.2023.25803

Declared interests

Prof Stephen Evans: “No conflicts of interest.”

Prof Craig Anderson: “No COI.”

Dr Richard Francis: “Dr Richard Francis has no conflicts of interest to declare.”

Prof Cathie Sudlow: “I have previously been closely involved in major international efforts on antithrombotic randomised trials and in particular  meta-analyses of these but not so closely in the last 15 years or so.”