Balancing uncertainty
How the PRESTIGE-AF project is finding answers to support vulnerable stroke patients
Stroke is one of the largest public health challenges around the world.
It’s the most common cause of adult-acquired disability, the second leading cause of death globally, and the second most frequent cause of dementia.
However, it’s not always clear how to treat stroke patients in order to prevent further stroke, particularly if they have other conditions.
Atrial fibrillation (AF) is the most common form of irregular heartbeat. Currently, around 6 million people suffer from AF in Europe and more than 30 million worldwide, but the prevalence of AF is expected to more than double in the next 3 decades.
The condition can cause blood clots to form in the heart, which can then travel to the brain and block arteries, causing a stroke. This type of stroke is called an ischaemic stroke, and approximately 15% of all ischaemic strokes are caused by atrial fibrillation.
People with atrial fibrillation are often prescribed blood-thinning medication called anticoagulants, which make it less likely for blood clots to form and thus can prevent ischaemic strokes.
However, anticoagulants can also increase the risk of bleeding, so they are not suitable for everyone. This is important to take into account for people with AF who also have other conditions.
For example, some people who have AF, especially those who receive blood-thinners, may experience a type of stroke caused by bleeding in the brain – an intracerebral haemorrhage (ICH). These people now have an increased risk of suffering both an ischaemic stroke (due to AF) and another ICH.
It is not known whether it is best for ICH patients with AF to take anticoagulant medication or not, as previous research studies have not included patients with both conditions.
“Almost 390,000 people in Europe have an ICH and 20% of these patients also have atrial fibrillation, and yet we don’t know the best way to treat those with both conditions,” says Professor Roland Veltkamp, Chair of Stroke Medicine at Imperial College London.
“We need to fill this gap in our clinical understanding in order to provide the best prevention stroke strategies for all patients.”
Professor Roland Veltkamp, Principal Investigator for the PRESTIGE-AF project.
Professor Roland Veltkamp, Principal Investigator for the PRESTIGE-AF project.
Introducing PRESTIGE-AF
Co-ordinated by Imperial College London and led by Professor Veltkamp, Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation (PRESTIGE-AF) is an EU-funded research project that brings together scientists and clinicians from 12 institutions across Europe to take a deep dive into the issues surrounding the treatment of ICH patients with AF.
Launched in 2017 and coming to an end in November 2024, the project has been hard at work researching the problem and are close to clarifying the best way to prevent further stroke in these patients following an international clinical trial.
The scope and scale of the problem
The key to tackling a problem is to understand the full extent of it. PRESTIGE-AF researchers have been actively looking into a variety of different aspects of the problem of how ICH patients with AF should be treated, including the views of clinicians, the future impact ICH will have on the population as a whole, and how gender inequality affects stroke treatment.
Highlighting uncertainty
PRESTIGE-AF researchers at the University of Liverpool were tasked with investigating how doctors and patients feel about and understand this issue.
Their research has shown that clinicians view the process of deciding on stroke prevention in patients with AF post-ICH as “challenging” due to considerable “clinical equipoise”. Effectively, this means that there is genuine uncertainty and honest disagreement amongst clinicians around the best way to treat these patients.
“Patients with ICH were largely excluded from seminal trials on the safety and efficacy of oral anticoagulants (OAC) in patients with AF, and much of the current evidence on the use of OAC and/or antiplatelets in patients with AF and ICH comes from observational studies,” says Professor Deirdre Lane, Professor of Cardiovascular Health at the University of Liverpool.
“These are major factors in the uncertainty of how to treat these patients, which PRESTIGE-AF is aiming to resolve.”
The PRESTIGE-AF team at the University of Liverpool. Left to right: Professor Deirdre Lane, Dr Elena Ivany, Professor Gregory Lip.
The PRESTIGE-AF team at the University of Liverpool. Left to right: Professor Deirdre Lane, Dr Elena Ivany, Professor Gregory Lip.
As part of their work, the team developed a toolkit to be used jointly by healthcare professionals and patients during consultations that address the topic of stroke prevention in ICH patients with AF.
The aim is to facilitate shared decision-making between healthcare professionals and patients and to promote patient understanding of their future stroke and bleeding risk.
Predicting the future impact of intracerebral haemorrhage
On an individual level, deciding on the best treatment for a patient will always be a matter of utmost importance.
However, we also need to understand the scale of the problem at hand at a population level and how that will change in the future.
The PRESTIGE-AF team based at King’s College London have been analysing the prevalence and impact of ICHs and predicting how this will change over the next few decades.
Their research predicts that deaths from ICH will increase by 8.9% across Europe by 2050 – with some countries expected to have increases of up to 74.4%.
While predictions saw a decline in individual risk, results showed that the absolute number of new cases and related deaths is expected to rise on a population level. The researchers believe this is because of Europe’s ageing population, who are particularly affected by the condition.
“With an ageing population across the UK and Europe and the anticipated increase in the proportion of older adults, the findings emphasise the importance of planning for rising healthcare demands and caregiving needs to tackle the anticipated surge in intracerebral haemorrhage cases and related deaths,” said Professor Yanzhong Wang, Professor of Statistics in Population Health, Kings College London.
Professor Yanzhong Wang
Professor Yanzhong Wang
These results show that PRESTIGE-AF’s goal of understanding how best to treat ICH patients with AF will only become more important as the burden of ICH increases over the next three decades.
Addressing inequality
Stroke is a leading cause of mortality among non-communicable diseases (NCDs) for both sexes. However, research shows that stroke is more detrimental to women.
“Specifically, women have higher overall lifetime risks of stroke along with higher rates of mortality and disabilities”, says Professor Valeria Caso, Professor of Neurology and Consultant Neurologist at the Stroke Unit, Santa Maria della Misericordia Hospital, University of Perugia, whose personal scientific focus has been stroke in women.
Professor Valeria Caso
Professor Valeria Caso
“In terms of risk factors for stroke, atrial fibrillation leads to higher incidence and more severe thromboembolic events (blood clotting) for women. Moreover, women tend to seek medical attention later than men as they are more likely to be living alone.”
Despite an increased risk with more detrimental outcomes, women’s presence in stroke research continues to be marginalised.
“To date, women have been under-represented in major randomised clinical trials (RCTs). The surrounding safety and efficacy results for women is not an accurate reflection of reality and this, in turn, means stroke prevention and treatment recommendations and guidelines are severely distorted.”
As part of PRESTIGE-AF, Professor Caso has been looking to understand the differences in attitudes between female and male stroke patients in clinical trials of stroke prevention, as well as the attitudes of physicians regarding the participation of women in such trials.
These preliminary results highlight the pressing need to increase women's participation in clinical trials.
Initial data from patient surveys show that men are slightly more inclined to participate in trials than women. Men indicated that the possibility of new treatments motivated their participation. In contrast, the primary concern for women who said that they were unwilling to take part in trials was the fear of being a ‘guinea pig’.
When surveyed about efforts to increase women’s participation, some physicians believed that participation rates among women might not significantly change despite efforts. Over half of physicians surveyed also stated that there are no gender-specific policies in their hospitals.
“These preliminary results highlight the pressing need to increase women's participation in clinical trials. By addressing potential mistrust and fear among women, we can create a more inclusive environment for trials, thereby improving access to care for women and advancing healthcare research.”
The PRESTIGE-AF Clinical Trial
At the heart of the PRESTIGE-AF project is a clinical trial that aims to definitively answer whether ICH patients with AF should take anticoagulants or not.
“As we have found, the current evidence on how to treat intracerebral patients with atrial fibrillation is inconclusive and has led to significant uncertainty for clinicians and patients involved in making these decisions,” says Dr Eleni Korompoki, a Clinical Research Fellow at Imperial College London.
“A randomised clinical trial is the best way to get the answers we need and resolve this uncertainty.”
Dr Eleni Korompoki
Dr Eleni Korompoki
A key challenge that faced the trial was recruiting patients to take part. This was due to the fragile condition that many ICH patients with AF find themselves in due to the often debilitating side effects ICHs can cause.
However, after a lot of hard work from PRESTIGE-AF’s partners and clinical sites, the project managed to recruit 319 patients from 63 hospitals in six countries across Europe.
Once enrolled onto the trial, participants were randomly assigned to one of two groups:
- Those who will receive a type of anticoagulant medication called direct oral anticoagulants (DOAC)
- Those who will not receive anticoagulant medication
The patients are then carefully monitored to assess how their condition progresses – in particular, whether they experience another stroke of any kind.
Sub-studies
Alongside the main trial are three optional sub-studies that participants in the trial can take part in, exploring other research areas.
One sub-study uses MRIs to see if any changes occur in trial participants’ brains without any noticeable symptoms.
Another looks at how easy it is to adhere to the anticoagulant medication treatment plan, as well as how well the medication is absorbed by the body, as this can be influenced by several factors.
And finally, one sub-study aims to develop tools for the prediction of individual risk of subsequent ischaemic or haemorrhagic stroke in ICH patients with AF.
It will look for clues in the participant’s blood and DNA, as well as information from clinical data and brain imaging, to see if anything could be indicative of a higher risk of suffering another stroke or could affect the participant’s response to anticoagulant medications.
Raising awareness
Alongside the scientific and clinical work taking place within the project, PRESTIGE-AF has also been running a comprehensive public engagement programme to engage a variety of audiences with the problem the project is trying to solve.
Much of this work was realised in the form of ‘Escape the Clinic!’, a pop-up escape room directly based on the research and trial taking place within PRESTIGE-AF.
Run between February 2023 and August 2024, the activity was showcased at 12 different events in the UK, Germany, Ireland and Switzerland, including science festivals, museum events, university outreach programmes, and major stroke conferences. In total, 502 ‘escape artists’ took part in 58 escape room sessions across this period.
Evaluation found that the majority of participants learnt something about PRESTIGE-AF, stroke and/or atrial fibrillation and enjoyed the escape room format, demonstrating the potential of pop-up escape rooms as effective tools to connect audiences with research by combining a popular and recognisable format with an unexpected topic.
All the data and learnings from the escape room have since been developed into a case study available to all who are interested in finding out more.
Next steps
With the PRESTIGE-AF clinical trial complete, data analysis is now underway. Researchers and clinicians from across the consortium are hard at work to understand everything that can be learnt from the vast and varied work undertaken within the project in order to benefit patients in the future.
“It’s been wonderful to bring together experts from across Europe to help tackle this vital problem,” says Professor Veltkamp. “It would not have been possible without the hard work of the whole consortium, the clinical teams at our recruiting hospitals, and of course the patients and their families who volunteered to help improve treatment for others who may face the same challenges as them.”
"Now that the clinical trial is complete, we hope that we will soon have definitive answers on how to treat this underserved group of patients."
Results from the project will continue to be made available, with key research and trial results expected to be published in early 2025. Keep an eye on the PRESTIGE-AF webpage for updates.
PRESTIGE-AF Partners
PRESTIGE-AF received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 754517. The sole responsibility for the content of this project lies with the authors. It does not necessarily reflect the opinion of the European Union. The European Commission is not responsible for any use that may be made of the information contained therein.
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