Research Question
To elucidate if the mechanism of action of DOACs to preserve cognitive function in patients with atrial fibrillation (AF) is due to the prevention of cerebral white matter lesions, reduction in incident silent brain infarcts, protection of cognitive neural tracts, or an overall decrease in the burden of vascular disease.
Background
AF is the most common heart rhythm abnormality, expected to double in prevalence in the next few decades, and leading to considerable burdens on the NHS and society. AF has a major impact on stroke, cognitive decline and vascular dementia, which are all key public health concerns. The newer direct oral anticoagulants (DOACs), if started at an earlier age, could provide protection against these adverse outcomes. This will be tested in DaRe2THINK, an innovative and NHS-embedded primary care trial funded by NIHR-HTA.
Aims & Objectives
In this sub-study, we aim to explain the reasons for cognitive decline and development of vascular dementia in patients with AF, and determine the mechanism of action of DOACs, separating out the effects on cerebrovascular disease from overall vascular disease burden.
Methods
DaRe2THINK is an individual-patient, open-label, event-driven randomised trial with 1:1 allocation to DOAC or no additional therapy (usual care), supported by extensive Patient and Public Involvement (PPI). The trial will use automated and targeted screening through NHS Primary Care, remote enrolment, and outcomes derived from NHS electronic records. This sub-study will recruit 160 patients from the 3000 that will be randomised in DaRe2THINK, with visits at baseline and 3-years comprising:
(1) Structural and functional brain magnetic resonance imaging (MRI) demonstrating change in white matter hyperintensities (WMH), cerebral infarction and connectivity/tractography;
(2) Structural and functional retinal imaging providing real-time assessment of vascular disease burden; and
(3) Cognitive function testing using gold-standard methods. Participants with claustrophobia or implanted clips/devices that prohibit the use of MRI will be excluded; all other patients recruited in the West Midlands will be approached consecutively until recruitment is completed. Sample size is based on the number of participants required for the primary outcome of new cerebral infarction or at least moderate WMH, and the key secondary outcome of retinal capillary density of the radial peripapillary capillary network.
Benefits for joining CPRD
- CPRD currently includes 1,337 practices in England (15% of all General Practices)
- Contribute to evidence-based medicine
- Ensure your patient population is represented in research evidence informing clinical guidance and best practice
- Earn extra income for the practice by taking part in questionnaires and clinical studies
- Your patients can take part in clinical studies
- Receive regular practice-level prescribing and patient safety quality improvement (QI) reports including patient case-finding and national practice benchmarking
- Case reviews from QI reports, questionnaires and research contribute towards annual appraisals and revalidation
How can you join the trial?
Joining is an easy, one-off process following which data automatically flows to CPRD.
If you and your General Practice currently use EMIS health as your patient medical record system and you are interested in taking part in DaRe2THINK please click this text to fill in a CPRD Practice Joining form.
Discover More ...
Use the links below to see tailored content for Healthcare Professionals and Patients, or find out more about results associated with the DaRe2THINK-NeuroVascular study.