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.
