Background
Atrial fibrillation (AF) is associated with a risk for stroke, transient
ischemic attack, and more recently with other forms of brain injury such
as cognitive impairment and dementia. In observational studies, the
relative risk of cognitive impairment and dementia among patients with
AF and a prior stroke is estimated between 2.43-2.70.1,
2
The Swiss Atrial Fibrillation (Swiss-AF) cohort evaluated for the
presence of stroke (clinical and subclinical) in a baseline cohort of
enrollees with AF that underwent MRI imaging (n=1,737 patients). Large
cortical and noncortical infarcts were found in 22% of patients, small
noncortical infarcts were found in 21%, microbleeds in 22%, and white
matter lesions in 99%.3 These infarcts, whether
labelled as clinical or subclinical were associated with cognitive
dysfunction. A more recent analysis from the Swiss-AF cohort reported
the outcomes of 1,227 patients that had a baseline brain MRI and another
2 years later. In this analysis, 2.3% patients had a new clinical
stroke or TIA. However, at least one infarct was detected in 5.5%
patients on the follow-up MRI.4 The presence of a new
stroke/cerebral infarct correlated with cognitive dysfunction, whether
the event was deemed clinical or subclinical by symptomatic diagnosis.
These studies derived from contemporarily managed populations with AF
continue to highlight the critical pathway of cerebral ischemic events
as a contributing mechanism for cognitive decline and dementia in
patients with AF.
Although there are randomized control data that show direct oral
anticoagulants (DOAC) lower risk of stroke and intracranial bleeding
compared to warfarin therapy5-7, there remains a lack
of data to determine if DOAC therapy may lower risk of cognitive decline
and dementia in comparison to warfarin therapy. There are mixed data in
observational studies that have assessed if DOACs, that are more
predictable and effective in prevention of stroke and intracranial
bleeds, may further lower risk compared to warfarin.8,
9
Dabigatran etexilate, an oral direct thrombin inhibitor, was studied
versus warfarin in patients with non-valvular AF.6Over a median follow-up of 2 years, dabigatran at 150 mg BID compared to
warfarin lowered the risk of stroke of systemic embolism and reduced
risk of hemorrhagic stroke. We also found in a community analysis of
DOAC therapies, dabigatran etexilate had the lowest observed dementia
rates despite the longest duration of follow-up.9
A recent consensus statement called for more prospective data regarding
the use, adherence, and efficacy of anticoagulation in AF to prevent
cognitive decline and dementia.10 TheC ognitive Decline and Dementia in A trialF ibrillation Patients (CAF) Trial (ClinicalTrials.gov
Identifier: NCT03061006) was proposed to determine if AF patients
randomized to dabigatran etexilate will have long-term higher cognition
scores and lower rates of dementia compared to dose-adjusted warfarin
(INR: 2.0-3.0).