Atrial fibrillation (AF) is a form of irregular heartbeat that can lead to blood clots and increase the risk of stroke. In order to reduce the risk of stroke, these patients are often treated with medications called anticoagulants, which include the traditional vitamin-K antagonists (VKAs), and the recently approved direct oral anticoagulants (DOACs). DOACs have been shown to be as beneficial as VKAs and easier to use, and are now recommended over VKAs. However, some patients with AF also have type 2 diabetes mellitus (T2DM) and they have a higher risk of stroke compared with patients with AF only. Having T2DM along with AF can affect the effectiveness and safety of DOACs. There have been very few studies on DOACs in these patients and it is unclear whether some DOACs are more effective in preventing stroke. Thus, we will form two groups of patients with both AF and T2DM, one group treated with apixaban and the other treated with rivaroxaban, the two most widely used DOACs in the UK. We will compare the number of patients with stroke in those treated with apixaban compared with those treated with rivaroxaban during follow-up. We will also compare the number of patients with a major bleeding in those treated with apixaban compared with those treated with rivaroxaban. This study will provide healthcare providers with evidence that will help them determine which of these two anticoagulants would be most appropriate for each of their individual patients.
Patients with both AF and T2DM are at increased risk of stroke compared with patients with AF only. Although DOACs are at least as effective and safe compared to VKAs in patients with AF and T2DM, little is known about whether some DOACs are more effective than others at preventing stroke in this population or associated with a lower risk of bleeding. Thus, we will conduct a population based cohort study to determine the effectiveness and safety of apixaban vs rivaroxaban, the two most commonly used DOACs in the UK, in patients with both AF and T2DM This study will be conducted by linking the CPRD, the HES inpatient database, and the Office for National Statistics (ONS) mortality database. We will form a cohort of patients with non valvular atrial fibrillation (NVAF) and T2DM newly treated with apixaban or rivaroxaban between 2013 and 2020. All patients will be followed until the first of the following events: ischaemic stroke or major bleeding (depending on the outcome being studied), death, oral anticoagulant discontinuation or switch, end of registration with the general practice, or end of the study period. The primary effectiveness outcome of interest will be a composite of hospitalization with incident ischaemic stroke, transient ischaemic attack or systemic embolism. The safety outcome of interest will be major bleeding or death from bleeding. We will use Cox proportional hazards models to estimate hazard ratios with 95% confidence intervals of the outcomes of interest associated with apixaban compared with rivaroxaban. In secondary analyses, we will assess whether this risk varies with duration of use. Propensity score (PS)-based standardised mortality ratio weighting will be used to address confounding. Several sensitivity analyses will be performed to assess the robustness of our results.
The effectiveness outcome of interest will be a composite of hospitalisation with an incident ischaemic stroke, transient ischaemic attack or systemic embolism (for simplicity, this composite outcome will be referred to as ischaemic stroke in the remaining of the protocol). The safety outcome of interest will be major bleeding. ICD-10 codes are listed in Appendix 1.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Jonathan Michaud - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Krishna Roy Chowdhury - Collaborator - McGill University
Laurent Azoulay - Collaborator - McGill University
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
HES Admitted Patient Care;ONS Death Registration Data