Periodic Reporting for period 5 - PRESTIGE-AF (PREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillation)
Período documentado: 2023-12-01 hasta 2024-11-30
Stroke a leading cause of death and long-term disability and its impact is expected to increase as the population ages. Strokes that are caused by bleeding in the brain (Intracerebral haemorrhage or ICH) account for only 10-15% of all strokes but are associated with a higher risk of disability and death compared to strokes caused by a blood clot (ischaemic stroke). At least 1-in-5 ICH survivors suffer from an irregular heart rhythm called atrial fibrillation (AF) which is a major risk factor for ischaemic stroke as it can cause blood clots to form in the heart. 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. However, survivors of ICH have a substantially increased risk of suffering another ICH and there is a concern that starting a DOAC may increase this risk. Consequently, stroke prevention in ICH patients with AF is an unresolved dilemma.
The 1st objective of PRESTIGE-AF is to determine if ICH patients with AF should be treated with DOAC for stroke prevention by assessing if treatment with DOACs is effective in preventing ischaemic stroke, compared to no anticoagulation, without substantially increasing the risk of ICH.
The 2nd objective is to improve the individual predictability of stroke in ICH patients with AF by personalising the preventive strategy using the results of risk modelling.
The 3rd 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 registry data, we will model outcomes with effect sizes of the DOACs in ICH populations and will model the replication of the trial findings within real-life settings.
The 4th objective is to investigate patient-centred aspects of preventive medicine in stroke by studying patients' attitudes towards antithrombotic therapy, psychosocial status, medication adherence and gender factors.
The 1st objective of PRESTIGE-AF is to determine if ICH patients with AF should be treated with DOAC for stroke prevention by assessing if treatment with DOACs is effective in preventing ischaemic stroke, compared to no anticoagulation, without substantially increasing the risk of ICH.
The 2nd objective is to improve the individual predictability of stroke in ICH patients with AF by personalising the preventive strategy using the results of risk modelling.
The 3rd 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 registry data, we will model outcomes with effect sizes of the DOACs in ICH populations and will model the replication of the trial findings within real-life settings.
The 4th objective is to investigate patient-centred aspects of preventive medicine in stroke by studying patients' attitudes towards antithrombotic therapy, psychosocial status, medication adherence and gender factors.
PRESTIGE-AF included a randomised clinical trial (RCT) that opened in 6 European countries at 75 hospital sites. Recruitment began in May 2019 and continued until November 2023. In total 319 participants were enrolled at 63 sites. Each participant was extensively characterised at the start of the trial, including collection of their medical history and brain imaging. Participants were followed up for a minimum of 6 months and a maximum of 36 months, with follow-up visits at month 1, 6, 12, 24 and 36.
Participants were offered the opportunity to participate in the following substudies:
The Predictive Modelling of Risk Substudy had multiple components, the basic prognostic score component consisted of all 319 trial patients, the blood-based biomarker component comprised of 124 participants and the genetic component comprised 131 participants. To evaluate ischaemic and ICH risk in these patients immunoassay techniques were used to assess blood-based biomarkers. Additionally, a smaller study using a subgroup of these participants explored new biomarkers for stroke and bleeding recurrence. Genetic analyses have been performed on genetic component participants to explore whether genetic variants facilitate risk stratification of ICH patients into risk categories for risk of incident IS or ICH recurrence. A brain imaging Substudy recruited 33 participants, who had an MRI brain scan at baseline and 12 months after enrolment. Brain imaging for all study participants was centrally assessed, investigating potential brain changes related to increased risk of stroke. The Pharmacology Substudy, which used dried blood spots to look at the levels of DOAC in a participant’s blood, recruited 50 participants.
To address public health impact, the project analysed data from the Global Burden of Disease study, together with population estimates from the United Nations Department of Economics and Social Affairs/Population Division. A manuscript summarising the risk and outcomes associated with ICH, including a forecast for the next 30 years in European countries was published in the Lancet Regional Health – Europe. We conducted a health economic analysis on the cost-effectiveness of direct oral anticoagulants versus no oral anticoagulation in ICH patients with AF based on the trial data from PRESTIGE-AF. The manuscript is completed and under internal review before submitting for publication.
Validation of trial outputs is important to bridge the potential gap between controlled environment from an RCT and routine clinical care. PRESTIGE-AF provided several scientific contributions that may help to put the results in perspective. A study published in Stroke (2022), assessed the risk of cerebrovascular events in survivors of ICH with AF. It found increased risks of ischemic events, recurrent ICH, and all-cause death, particularly in those with higher CHA2DS2-VASc scores. Patients resuming oral anticoagulants had a higher risk of ischaemic events but lower mortality. In addition to scientific manuscripts, consortium participants also presented project outputs multiple times at the World’s largest cardiology conference (European Society of Cardiology) that may help to increase awareness and underscore the needs for careful management in this high-risk group of patients.
A qualitative Substudy investigating the underrepresentation of women in stroke prevention trials will providing crucial insights into potential biases in patient selection for clinical trials. A manuscript will incorporate qualitative data through case scenarios, enriching the understanding of the decision-making process.
Participants were offered the opportunity to participate in the following substudies:
The Predictive Modelling of Risk Substudy had multiple components, the basic prognostic score component consisted of all 319 trial patients, the blood-based biomarker component comprised of 124 participants and the genetic component comprised 131 participants. To evaluate ischaemic and ICH risk in these patients immunoassay techniques were used to assess blood-based biomarkers. Additionally, a smaller study using a subgroup of these participants explored new biomarkers for stroke and bleeding recurrence. Genetic analyses have been performed on genetic component participants to explore whether genetic variants facilitate risk stratification of ICH patients into risk categories for risk of incident IS or ICH recurrence. A brain imaging Substudy recruited 33 participants, who had an MRI brain scan at baseline and 12 months after enrolment. Brain imaging for all study participants was centrally assessed, investigating potential brain changes related to increased risk of stroke. The Pharmacology Substudy, which used dried blood spots to look at the levels of DOAC in a participant’s blood, recruited 50 participants.
To address public health impact, the project analysed data from the Global Burden of Disease study, together with population estimates from the United Nations Department of Economics and Social Affairs/Population Division. A manuscript summarising the risk and outcomes associated with ICH, including a forecast for the next 30 years in European countries was published in the Lancet Regional Health – Europe. We conducted a health economic analysis on the cost-effectiveness of direct oral anticoagulants versus no oral anticoagulation in ICH patients with AF based on the trial data from PRESTIGE-AF. The manuscript is completed and under internal review before submitting for publication.
Validation of trial outputs is important to bridge the potential gap between controlled environment from an RCT and routine clinical care. PRESTIGE-AF provided several scientific contributions that may help to put the results in perspective. A study published in Stroke (2022), assessed the risk of cerebrovascular events in survivors of ICH with AF. It found increased risks of ischemic events, recurrent ICH, and all-cause death, particularly in those with higher CHA2DS2-VASc scores. Patients resuming oral anticoagulants had a higher risk of ischaemic events but lower mortality. In addition to scientific manuscripts, consortium participants also presented project outputs multiple times at the World’s largest cardiology conference (European Society of Cardiology) that may help to increase awareness and underscore the needs for careful management in this high-risk group of patients.
A qualitative Substudy investigating the underrepresentation of women in stroke prevention trials will providing crucial insights into potential biases in patient selection for clinical trials. A manuscript will incorporate qualitative data through case scenarios, enriching the understanding of the decision-making process.
The findings of another 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 stroke prevention therapy reported patients’ desire to maintain an acceptable quality of life as the main driver of treatment decisions. This paper was published in the European Journal of Cardiovascular Nursing in January 2025. 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 project, PRESTIGE-AF produced 22 publications, took part in 44 conferences/events, published 23 stories on its website, and amassed 298 Twitter followers.
Over the project, PRESTIGE-AF produced 22 publications, took part in 44 conferences/events, published 23 stories on its website, and amassed 298 Twitter followers.