Neuro-vascular mechanisms of direct oral anticoagulant therapy in younger patients with atrial fibrillation: the DaRe2THINK-NV sub-study
Study Code / Acronym
DaRe2THINK-NVAward Number
NIHR132974Award Type
EME Researcher LedProgramme
Efficacy and Mechanism EvaluationStatus / Stage
ActiveDates
7 February 2021 -7 January 2025
Duration (calculated)
03 years 11 monthsFunder(s)
NIHRFunding Amount
£406,301.30Funder/Grant study page
NIHRContracted Centre
University of BirminghamContracted Centre Webpage
Principal Investigator
Professor Dipak KotechaPI Contact
d.kotecha@bham.ac.ukPI ORCID
0000-0002-2570-9812WHO Catergories
Understanding Underlying DiseaseDisease Type
Vascular Dementia (VD)CPEC Review Info
| Reference ID | 24 |
|---|---|
| Researcher | Reside Team |
| Published | 12/06/2023 |
Data
| Study Code / Acronym | DaRe2THINK-NV |
|---|---|
| Award Number | NIHR132974 |
| Status / Stage | Active |
| Start Date | 20210207 |
| End Date | 20250107 |
| Duration (calculated) | 03 years 11 months |
| Funder/Grant study page | NIHR |
| Contracted Centre | University of Birmingham |
| Contracted Centre Webpage | |
| Funding Amount | £406,301.30 |
Abstract
To elucidate if the mechanism of action of direct oral anticoagulants (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 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 the UK National Institute for Health Research (NIHR). Aims and 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 tractography; (2) Structural and functional retinal imaging providing real-time assessment of vascular disease burden; and (3) Cognitive function testing using best-practice methods. Participants with claustrophobia or implanted clips/devices that prohibit the use of MRI will be excluded; all other patients recruited in/near 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 on follow-up MRI or at least moderate WMH, and the key secondary outcome of retinal capillary density of the radial peripapillary capillary network. Timelines for delivery: Total duration 48 months, including a 6-month period for baseline scans within 3 months of patient randomisation, and 4-6 months for follow-up scans after a 3-year interval. Anticipated impact and dissemination: Mechanistic understanding of the role of DOACs in prevention of micro and macro-vascular disease both within and outside the brain could facilitate personalised approaches to prevention of cognitive decline and vascular dementia in younger patients with AF, as well as other multi-system thrombo-inflammatory conditions. Causative assessment of cognitive decline with interval vascular imaging could inform the use of simple preventative measures within NHS primary care. Results will be disseminated through the NIHR Primary Care Clinical Research Network and the PPI team assisted by AF patient support groups.
Aims
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.