Atrial fibrillation is the most common heart rhythm disturbance in the UK and occurs more frequently as people age. People with atrial fibrillation are five times more likely to have a stroke due to blood clots travelling from their heart to the brain than those without atrial fibrillation. Therefore, individuals with atrial fibrillation are often recommended to take blood-thinning drugs (anticoagulants) to prevent stroke. Recent evidence has shown that having atrial fibrillation is also linked to dementia and other problems with memory such as mild cognitive impairment. However, while taking anticoagulant drugs may help to delay the onset of dementia among individuals with atrial fibrillation, we do not know which types of anticoagulants drugs are most beneficial and for which groups of patients. This study will follow older individuals with newly diagnosed atrial fibrillation identified in UK healthcare data to investigate the effect of different anticoagulant drug prescriptions on rates of dementia and mild cognitive impairment. This will help clinicians to make informed choices about prescribing anticoagulants for older individuals with new atrial fibrillation.
Atrial fibrillation is common: the lifetime risk is 37% among people aged 55 years and over in the UK. An established risk factor for stroke, it is also associated with an increased risk of dementia and cognitive decline. While guidance from the National Institute of Health and Care Excellence recommends oral anticoagulation for stroke prevention among certain groups with atrial fibrillation, the effect of anticoagulant choice on the incidence of dementia and mild cognitive impairment is not well-understood. In particular, whether dementia risk is affected by drug class (vitamin K antagonists such as warfarin versus direct oral anticoagulants such as apixaban), timing of prescriptions e.g. in relation to stroke and any interaction with patient demographic or clinical characteristics is not well-understood. This is important to inform prescribing policy.
In this cohort study, we will use routinely collected primary and secondary care data to investigate the effect of vitamin K antagonists and direct oral anticoagulants prescribed to older individuals with a new diagnosis of atrial fibrillation on rates of incident dementia and mild cognitive impairment. We will use multivariable Cox regression models to adjust for potential confounding factors, and assess (for vitamin K antagonists) whether effects vary by time in the therapeutic range. We will also undertake a range of sensitivity analyses. These include (1) expanding our outcome definition to include a broader range of causes of dementia, (2) restricting to individuals with linked primary and secondary care data only to improve ascertainment of atrial fibrillation and outcomes, and (3) restricting to individuals diagnosed with atrial fibrillation in primary care to improve accuracy of data on the timing on first anticoagulant prescription. We will carry out similar analyses in a population of stroke survivors to investigate the effect of prior atrial fibrillation and anticoagulant choice on the incidence of post-stroke dementia.
Primary
Incident dementia (all-cause)
Secondary
Incident dementia (cause-specific i.e. vascular, Alzheimers disease, mixed etc)
Incident mild cognitive impairment
Charlotte Warren-Gash - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Charlotte Warren-Gash - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Emma Powell - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Fernanda Tapia - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Kevin Wing - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Sharon Cadogan - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Suhail Ismail Shiekh - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Yun "Angel" Wong - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation