On 11-12 March, members of the PRESTIGE-AF team from Imperial College London ran the PRESTIGE-AF Escape Room at the European Life After Stroke Forum (ELASF) 2024 in Dublin, Ireland.

Launched in 2019 by Stroke Alliance For Europe (SAFE), the conference aims to create an opportunity at least once a year for those who operate in the area of life after stroke, whether researchers, scientists, medical professionals, health policymakers, advocacy, or support groups, stroke survivors and their carers, to come together and share and network.

The Forum shone a light on a range of important areas, including how we can highlight the voices of stroke survivors, gender disparities and mental health in life after stroke, and secondary stroke prevention.

As part of the programme, PRESTIGE-AF presented the escape room as a novel form of communicating research and ran four sessions for the attendees to try. Working as a team, the groups had to tackle various puzzles – from a brain MRI scan jigsaw to performing a blood spot that magically made the code to a locked case appear – in order to find out the information required to enrol a participant onto the PRESTIGE-AF clinical trial.

It was wonderful being able to showcase our flagship engagement activity for people with such a wide range of backgrounds and experiences with stroke, including getting valuable insights from stroke survivors and patient advocates.

New PRESTIGE-AF research predicts that deaths from intracerebral haemorrhages (ICH) will increase by 8.9% across Europe by 2050 – with some countries expected to have increases of up to 74.4%.

Published in The Lancet Regional Health – Europe by PRESTIGE-AF researchers based at King’s College London, the study says that the number of cases and deaths from ICH is set to increase across the continent, despite a downtrend observed in the past thirty years.

The research shows that PRESTIGE-AF’s goal of understanding how best to treat ICH patients with atrial fibrillation will only become more important as the burden of ICH increases over the next three decades.

Effects of an ageing population

While predications 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 and contribute significantly to the growing burden.

“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.

A need for country-specific plans

The research shows significant variation in predicted ICH burden across the continent. The top five countries with the biggest increase in deaths are:

• Ireland – 74.4%
• Cyprus – 74.2%
• Luxembourg – 70.7%
• Netherlands – 45%
• Finland – 40.7%

This highlights the need for country-specific action plans and a need for ongoing research to monitor epidemiological trends, risk factor prevalence, and disease mechanisms, enabling refined projections and targeted interventions against ICH.

“We developed a sophisticated modelling framework to anticipate the future health burden of intracerebral haemorrhage,” said Hatem A Wafa, Research Associate and Trial Statistician, Kings College London. “By considering multiple scenarios, the study offered a range of potential trajectories between 2019 and 2050. Key factors that contribute to the rise of deaths are high blood pressure, high blood sugar and obesity.”

Unlike previous studies, this research not only projected an increase in ICH cases but also offers unique insights into the potential trajectories and implications for healthcare systems.

By unveiling the potential challenges and opportunities, the authors hope that this insight can guide policymakers and healthcare professionals in developing strategies to tackle the anticipated surge in ICH cases and related deaths and the evolving landscape of stroke in the coming decades.

On 19 January, members of the PRESTIGE-AF team from Imperial College London ran the PRESTIGE-AF Escape Room at the University of Würzburg’s 6^th Joint Winter School in translational medicine and clinical science.

This year’s theme was ‘Stroke: research, challenges and international perspectives’, and included presentations on topics ranging from stroke epidemiology and risk factors to drivers in inequalities to post-stroke care.

As part of the programme, PRESTIGE-AF presented the escape room as a novel form of communicating research and ran four sessions for the attendees to try. Working as a team, the groups had to tackle various puzzles – from a brain MRI scan jigsaw to performing a blood spot that magically made the code to a locked case appear – in order to find out the information required to enrol a patient onto the PRESTIGE-AF clinical trial.

Hard work and determination meant all teams managed to enrol their patient and escape the clinic, and feedback showed that the participants enjoyed themselves and valued the escape room format, with one participant commenting that they “got to know a really cool new form of science communication. I’ve never done a medicine themed escape room before and really enjoyed doing one!”

It was great to be able to take our flagship engagement activity to another of PRESTIGE-AF’s partner institutions, and we look forward to continuing our work on this throughout the year.

As of midnight on 30 November 2023, PRESTIGE-AF has officially closed recruitment to the PRESTIGE-AF clinical trial with a total of 319 participants.

After a lot of hard work from across the consortium and our clinical sites, the team managed to recruit 20 participants over the past month – the highest recruiting month since the project began – leading to the study having 5 more participants than the 314 estimated as part of our power calculations.

The hard work doesn’t stop here though as the team continues its patient follow up before analysing all our data. We look forward to the time when we can share our results and help resolve the uncertainty around how best to treat intracerebral haemorrhage patients with atrial fibrillation.

Resolving an area of clinical uncertainty

PRESTIGE-AF 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”.

“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,” said Elena Ivany, Research Associate at the University of Liverpool’s Centre for Cardiovascular Science. “These are major factors in the uncertainty of how to treat these patients, which PRESTIGE-AF is aiming to resolve.”

Stroke remains one of the largest public health challenges around the world, being the most common cause of adult-acquired disability, the second leading cause of death globally, and the second most frequent cause of dementia. In addition, its impact is expected to further increase in the coming decades due to the ageing population.

Improving our understanding of how to prevent stroke in all groups is vital to lessening this burden and saving lives.

The best way to prevent further stroke in intracerebral haemorrhage (ICH) survivors with atrial fibrillation (AF) continues to be an area of uncertainty for clinicians.

Left atrial appendage occlusion (LAAO) is considered an alternative treatment option to anticoagulants for these patients.

However, ICH survivors with AF have historically been excluded from randomised controlled trials about LAAO, meaning there is only limited evidence from observational studies regarding its role in treating this high-risk patient population.

In conversation with Professor Gregory Lip

In this interview, Dr Eleni Korompoki and Professor Gregory Lip discuss the evidence behind LAAO for ICH survivors with AF, and what the right course of action might be for these patients.

Watch their conversation on YouTube:

Or listen on SoundCloud:

Take home messages

After discussing with Professor Lip, Dr Korompoki summarises the take home messages as the following:

1. Compared to trials studying oral anticoagulants for stroke prevention in cases of atrial fibrillation, randomised controlled trials comparing LAAO and anticoagulation were very small;
2. Available data for LAAO in ICH patients with AF is only based on observational studies with substantial risk of bias;
3. Enrolling ICH patients with AF into randomised controlled trials comparing LAAO and anticoagulants is currently the best option for these patients.

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Use the following guide to direct yourself to different sections of the conversation:

00:00 – introduction

01:55 – could you please give us an overview of data supporting stroke prevention in patients with AF by LAAO?

04:27 – what are the strengths and limitations of available trials on LAAO?

07:29 – what about PRAGUE-17 that compares LAAO with direct oral anticoagulants?

09:20 – looking specifically at ICH patients with AF, what is the current evidence for stroke prevention using LAAO?

11:10 – what are the limitations of LAAO for these patients?

12:59 – what about anti-thrombotics post-LAAO?

13:55 – in your opinion, should stroke centres recommend participation in randomised controlled trials of anticoagulation vs no anticoagulation, or refer patients for LAAO?

15:39 – how many ICH patients with AF do you usually refer to LAAO? The majority or just a few?

16:58 – in conclusion, what is your current recommendation for stroke prevention for ICH patients with AF?

20:00 – take home messages

With an ageing population, clinicians are more frequently encountering patients with atrial fibrillation (AF) who are also at risk of intracerebral haemorrhage due to cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a condition common among elderly patients that is characterised by β-amyloid deposition in small blood vessels in the brain, making them more fragile.

Whilst this is often asymptomatic for most patients, CAA increases the risk of a brain haemorrhage when combined with other risk factors, such as blood pressure fluctuations or the use of anticoagulants.

The presence and severity of CAA should be considered when deciding on the best stroke-prevention treatment for patients with AF and a recent lobar intracerebral haemorrhage, as they may benefit from anticoagulant treatment.

In conversation with Dr Andreas Charidimou

Given the current scarcity of randomised trial data to guide stroke prevention strategies, Dr Lucio D’Anna, a consultant in stroke medicine at Imperial College Healthcare NHS Trust, discusses the use of pharmacologic and non-pharmacologic approaches, such as left atrial appendage occlusion, to decrease stroke risk in this challenging patient group with Dr Andreas Charidimou, an instructor in neurology at Boston University Medical Center.

Watch on YouTube:

Or you can listen to their conversation on SoundCloud:

Take home messages

After discussing with Dr Charidimou, Dr D’Anna summarises the take home messages as the following:

1. Given limited data from randomised trials regarding anticoagulation in intracerebral haemorrhage patients with probable cerebral amyloid angiopathy and atrial fibrillation, currently the best choice for patients is to enrol them into randomised clinical trials such as PRESTIGE-AF.
2. There is not enough evidence to support the conclusion that left atrial appendage occlusion is safe and effective in intracerebral haemorrhage patients with cerebral amyloid angiopathy and atrial fibrillation.
3. The risk of thromboembolism in patients with atrial fibrillation after an intracerebral haemorrhage should be weighted carefully even if the patient has imaging markers of cerebral amyloid angiopathy such as cerebral microbleeds, cortical superficial siderosis and white matter hyperintensities.

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Use the following guide to direct yourself to different sections of the conversation:

00:00 – introduction

01:45 – what is cerebral amyloid angiopathy (CAA)?

03:35 – why is it important to consider CAA in patient management?

05:03 – what are the signs and symptoms of CAA?

06:34 – what are the main neuroimaging features that can be related to higher risk of future intracerebral haemorrhage?

09:20 – what are the updates recently made to the Boston criteria for CAA diagnosis?

13:21 – what is the risk of an ischaemic stroke for a patient with atrial fibrillation and CAA who recently suffered an intracerebral haemorrhage?

15:17 – what is the evidence to start anticoagulants in these patients?

16:55 – when do you think a patient with atrial fibrillation and CAA would be unsuitable for anticoagulation?

18:17 – what are observational studies telling us about the risk of vascular events in patients with CAA?

20:05 – how does CAA affect the risk of a recurrent haemorrhage for patients who have had a lobar intracerebral haemorrhage?

21:30 – and how about for deep intracerebral haemorrhages?

22:45 – what is the role of microbleeds in the risk of intracerebral haemorrhages for patients with/without CAA?

25:26 – should we enrol patients with a lobar intracerebral haemorrhage and CAA into an anticoagulant clinical trial?

27:38 – are there particular patients you wouldn’t recommend participating in one of these trials?

28:58 – do you think left atrial appendage occlusion could be a better option for stroke prevention for these patients?

30:07 – do you routinely send these patients for left atrial appendage occlusion?

31:14 – summarise what you currently think is the best management for patients with intracerebral haemorrhage and CAA?

33:04 – take home messages

New materials to support clinicians in involving intracerebral haemorrhage (ICH) patients with atrial fibrillation (AF) in the decision-making process for their treatment are now available as part of the PRESTIGE-AF project.

Why have these materials been produced?

PRESTIGE-AF-funded 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”.

“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 Elena Ivany, Research Associate at the University of Liverpool’s Centre for Cardiovascular Science. “These are major factors in the uncertainty of how to treat these patients, which PRESTIGE-AF is aiming to resolve.”

Physicians who are required to advise on appropriate stroke prevention therapy for patients with AF and ICH have described a desire to involve patients in the decision-making process. However, at the same time, there is some uncertainty as to how shared decision-making is best achieved.

Supporting shared decision-making

Developed by the University of Liverpool team, these educational materials aim to facilitate patient involvement in the decision-making process by providing physicians with a range of information that can be used during patient-facing consultations.

The materials that are included in the pack are based on key patient-related outcomes related to stroke prevention in AF, such as risk of ischaemic/thromboembolic events, risk of bleeding, and lifestyle considerations.

Physicians may wish to use the materials to initiate conversations about patients’ goals of care and to identify patients’ preferred treatments or therapies for stroke prevention. Some of the materials are interactive, while others can be used as supporting information to promote patient understanding of the benefits and risks of OAC.

Additionally, there are links to resources that physicians may wish to share with patients who are interested in learning more about their disease and the stroke prevention therapies available to them.

The materials have been peer-reviewed by physicians and patients to ensure that the information provided is clinically relevant and accurate.

Overall, it is hoped that these educational materials can be a positive tool to promoting patient engagement in discussions about stroke prevention therapy in individuals with AF and ICH.