Atrial fibrillation (AF) is a common heart disease, characterized by irregular heart rhythm. People with AF are at increased risk of stroke. Furthermore, they face higher risk of developing dementia. People with AF are often prescribed drugs called anticoagulants for stroke prevention. There is also evidence that anticoagulants can decrease the risk of dementia in patients with AF. There are two types of anticoagulants: vitamin-K antagonists (VKAs) and direct oral anticoagulants (DOACs). DOACs are recommended over VKAs for stroke prevention because they have comparable efficacy and are easier to use. While there is evidence that DOACs are better at preventing dementia compared with VKAs, it is unclear whether there are differences between DOACs. Apixaban and rivaroxaban are the two most commonly prescribed DOACs. Thus, the main objective of our study is to assess whether one of these two DOACs - apixaban or rivaroxaban – provides more benefit in the prevention of dementia. We will form two groups of patients with AF, one group treated with apixaban and the other treated with rivaroxaban. We will compare the number of patients who are diagnosed with dementia during follow-up in those treated with apixaban with those treated with rivaroxaban. We will then study the benefit according to the duration of the oral anticoagulant treatment, and in different subgroups of patients. This study will provide important information to inform the choice of a particular DOAC in patients with AF.
Atrial fibrillation (AF) is the most common cardiac dysrhythmia. Oral anticoagulation is essential in the management of AF to prevent stroke occurrence. It can also maintain cognitive functions by decreasing the frequency of silent strokes, microembolisms, or global cerebral hypoperfusion. Direct oral anticoagulants (DOACs) were shown to be at least as effective in preventing ischemic stroke or systemic embolism as warfarin, with a lower risk of major bleeding. There is also moderate evidence that DOACs as a class is associated with a decreased risk of dementia compared to warfarin. However, it remains unclear which DOACs have a higher protective effect against dementia.
We will conduct a population-based cohort study to assess the potential decreased risk of dementia associated with apixaban compared with rivaroxaban, the two most commonly used DOACs. We will assemble a cohort of all patients in the CPRD, aged 50 years or more, newly diagnosed with AF between 2011 and 2021 and initiating apixaban or rivaroxaban. Propensity score methods will be used to control for confounding. We will calculate incidence rates of dementia with 95% CIs for each exposure group, based on the Poisson distribution. Cox proportional hazards models will be fit to estimate weighted HRs and 95% CIs of dementia associated with apixaban compared with rivaroxaban. In secondary analyses, we will assess whether there is a duration-response relation and whether there is effect measure modification by age, sex, history of comorbidities, and whether the association varies by type of dementia. Several sensitivity analyses will be performed to assess the robustness of our results.
The primary outcome of interest will be a composite of all forms of dementia, defined using relevant Read codes and SNOMED Clinical Terms (listed in appendix 2). Secondary outcomes will include different sub-types of dementia, including Alzheimer’s disease, vascular dementia, and non-otherwise specified/other dementias.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
Alvi Rahman - Collaborator - McGill University
Ekaterina Pazukhina - Collaborator - McGill University
Erica Moodie - Collaborator - McGill University
James Brophy - Collaborator - McGill University
Jean-François Boivin - Collaborator - McGill University
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