Periodic Reporting for period 4 - PRESTIGE-AF (PREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillation)
Periodo di rendicontazione: 2022-06-01 al 2023-11-30
Stroke is one of the leading causes of death and long-term disability worldwide and its impact is expected to increase even further with the ageing of populations. Strokes that are caused by bleeding in the brain (Intracerebral haemorrhage or ICH) account for only 10-15% of all strokes but they are associated with a higher risk of disability and death compared to strokes caused by a blood clot (ischaemic stroke). At least 20% of ICH survivors suffer from an irregular heartbeat called atrial fibrillation (AF) which can cause blood clots to form in the heart, and is a major risk factor for ischaemic stroke. In patients with AF, ischaemic stroke can be effectively prevented by taking medications called direct oral anticoagulants (DOACs) which lower the risk of blood clots forming. However, survivors of ICH have a substantially increased risk of suffering another ICH, and there is a concern that starting anticoagulants may increase the risk of them having another ICH. Consequently, stroke prevention in ICH patients with AF is an unresolved dilemma.
The first objective of the project is to determine whether ICH patients who have AF should be treated with DOAC for stroke prevention or not. PRESTIGE-AF will assess whether treatment with DOACs is more effective in preventing ischaemic stroke (compared to not taking DOAC) without substantially increasing the risk of ICH recurrence.
The second objective of the study is to improve the individual predictability of stroke in ICH patients with AF. We intend to personalise the preventive strategy to individual patients using the results of risk modelling.
The third objective is to address public health and health economic implications by estimating the effects of the trial data to the general stroke population. Using large-scale European and Asian registry data, we will model outcomes with effect sizes of the DOACs in different ICH patient populations and will model the replication of the trial findings within real-life settings.
The fourth objective is to investigate patient-centred aspects of preventive medicine in stroke. We will study the potential impact that patients' attitudes towards antithrombotic therapy, and their psychosocial status, have on adherence to medication and on clinical outcomes. Participant’s adherence to their medication will be monitored throughout the trial using questionnaires and blood drug levels. We will also strive to identify physician and patient factors that may underlie the under-representation of women in stroke prevention trials to inform future trials of cardiovascular prevention.
The first objective of the project is to determine whether ICH patients who have AF should be treated with DOAC for stroke prevention or not. PRESTIGE-AF will assess whether treatment with DOACs is more effective in preventing ischaemic stroke (compared to not taking DOAC) without substantially increasing the risk of ICH recurrence.
The second objective of the study is to improve the individual predictability of stroke in ICH patients with AF. We intend to personalise the preventive strategy to individual patients using the results of risk modelling.
The third objective is to address public health and health economic implications by estimating the effects of the trial data to the general stroke population. Using large-scale European and Asian registry data, we will model outcomes with effect sizes of the DOACs in different ICH patient populations and will model the replication of the trial findings within real-life settings.
The fourth objective is to investigate patient-centred aspects of preventive medicine in stroke. We will study the potential impact that patients' attitudes towards antithrombotic therapy, and their psychosocial status, have on adherence to medication and on clinical outcomes. Participant’s adherence to their medication will be monitored throughout the trial using questionnaires and blood drug levels. We will also strive to identify physician and patient factors that may underlie the under-representation of women in stroke prevention trials to inform future trials of cardiovascular prevention.
The PRESTIGE-AF Study includes the randomised clinical trial and 3 substudies. The trial protocol has been approved by ethics and regulatory authorities in 6 European countries. All aspects of the trial infrastructure including data entry platforms, safety reporting, event adjudication, data monitoring, and delivery of supplies, are firmly established. The criteria to take part in the clinical trial has been amended so that patients who have cognitive decline, and are not able to make decisions for themselves, can be included with the agreement of their next of kin. This means that our results will be more representative of the patient group because cognitive decline is common after ICH. It is a great success of the project that this has been approved in 5 countries as some authorities are reluctant to approve this in prevention studies.
At the close of recruitment on 30th November 2023, PRESTIGE-AF had 319 participants enrolled into the trial. The team have worked hard to boost recruitment, which has been successful, with the average monthly recruitment from June 2022 being over 10 participants per month which was increased from under 6 per month for the previous period. Of the 75 hospitals where the trial was opened, 54 still have participants in follow-up. Each participant is extensively characterised at the start of the trial, including collection of their medical history and brain imaging.
They are offered participation in the following substudies, which provide further valuable data:
Predictive Modelling of Risk Substudy where participants have blood-based biomarkers and genetic samples collected, has recruited 131 participants. Longitudinal Neuroimaging Substudy has recruited 43 participants, each will have an additional MRI brain scan at 12 months after inclusion. Pharmacology Substudy, which uses dried blood spots to look at the levels of DOAC in a participant’s blood, has recruited 48 participants.
The substudies are recruiting participants until May 2024.
To address public health impact, the project is using previously collected information from the Global Burden of Disease study, together with population estimates from the United Nations Department of Economics and Social Affairs/Population Division. We have conducted comprehensive analyses and compiled a manuscript summarising the risk and outcomes associated with ICH, including a forecast for the next 30 years. This manuscript has been submitted for publication and is currently under review at the Lancet Regional Health – Europe. The ongoing investigation into the underrepresentation of women in stroke prevention trials is progressing. Data collection from physicians' questionnaires is nearing completion, providing crucial insights into potential biases in patient selection for clinical trials. The paper will incorporate qualitative data through case scenarios, enriching the understanding of the decision-making process.
The findings of a qualitative substudy that examined the attitudes of doctors towards stroke prevention management of AF patients who have survived an ICH were presented orally at the British Cardiovascular Society conference in June 2022 and published in Thrombosis and Haemostasis in September 2022. Another substudy exploring the views of patients with ICH and AF on antithrombotic therapy reported patients’ desire to maintain an acceptable quality of life as the main driver of treatment decisions. The paper is currently in submission to PLoS ONE. Educational materials for physicians to support patient decision-making for stroke prevention were developed and published on the PRESTIGE-AF website in March 2023.
Over the course of the project, PRESTIGE-AF has produced 22 publications, taken part in 44 conferences and events, published 23 news stories on its website, and amassed 298 Twitter followers.
At the close of recruitment on 30th November 2023, PRESTIGE-AF had 319 participants enrolled into the trial. The team have worked hard to boost recruitment, which has been successful, with the average monthly recruitment from June 2022 being over 10 participants per month which was increased from under 6 per month for the previous period. Of the 75 hospitals where the trial was opened, 54 still have participants in follow-up. Each participant is extensively characterised at the start of the trial, including collection of their medical history and brain imaging.
They are offered participation in the following substudies, which provide further valuable data:
Predictive Modelling of Risk Substudy where participants have blood-based biomarkers and genetic samples collected, has recruited 131 participants. Longitudinal Neuroimaging Substudy has recruited 43 participants, each will have an additional MRI brain scan at 12 months after inclusion. Pharmacology Substudy, which uses dried blood spots to look at the levels of DOAC in a participant’s blood, has recruited 48 participants.
The substudies are recruiting participants until May 2024.
To address public health impact, the project is using previously collected information from the Global Burden of Disease study, together with population estimates from the United Nations Department of Economics and Social Affairs/Population Division. We have conducted comprehensive analyses and compiled a manuscript summarising the risk and outcomes associated with ICH, including a forecast for the next 30 years. This manuscript has been submitted for publication and is currently under review at the Lancet Regional Health – Europe. The ongoing investigation into the underrepresentation of women in stroke prevention trials is progressing. Data collection from physicians' questionnaires is nearing completion, providing crucial insights into potential biases in patient selection for clinical trials. The paper will incorporate qualitative data through case scenarios, enriching the understanding of the decision-making process.
The findings of a qualitative substudy that examined the attitudes of doctors towards stroke prevention management of AF patients who have survived an ICH were presented orally at the British Cardiovascular Society conference in June 2022 and published in Thrombosis and Haemostasis in September 2022. Another substudy exploring the views of patients with ICH and AF on antithrombotic therapy reported patients’ desire to maintain an acceptable quality of life as the main driver of treatment decisions. The paper is currently in submission to PLoS ONE. Educational materials for physicians to support patient decision-making for stroke prevention were developed and published on the PRESTIGE-AF website in March 2023.
Over the course of the project, PRESTIGE-AF has produced 22 publications, taken part in 44 conferences and events, published 23 news stories on its website, and amassed 298 Twitter followers.
PRESTIGE-AF addresses an important unmet need for developing prevention concepts in a highly vulnerable group of stroke patients, namely those with ICH and AF. Effective prevention of recurrent strokes in these patients will prevent the devastating consequences for the individual and their families and will reduce societal and healthcare costs. PRESTIGE-AF will deliver new guidance on effective treatment of ICH patients with AF. It will establish a personalised approach of individual risk prediction that integrates the knowledge of clinical characteristics as well as biological data including biomarkers, genetics, and neuroimaging. The project will also simulate the population impact of the trial using data from large-scale registries derived from real life settings and perform health economic modelling. PRESTIGE-AF will investigate patient-centred aspects such as adherence to medication, patients’ and physicians´ attitudes towards anticoagulation, and gender aspects in stroke prevention research.