The protocol is updated based on the approved protocol reference ID 20_136. The study period has been updated to include 2023/2024 data, the most recent data available from CPRD.
Atrial fibrillation (AF), the commonest form of arrythmia, is characterized by irregular, rapid heartbeat and increases the risk of stroke (five times), heart failure, and death (two-fold). AF treatment include oral anticoagulants, which prevent blood clots, the main driver of the associated stroke risk. Traditionally warfarin, a vitamin K antagonist (VKA), was mainly used however it requires careful dosage adjustment and regular blood tests to be used safely. Direct oral anticoagulant (DOACs) are easier to use and have been shown in clinical trials to not only reduce stroke risk in AF patients but also have a lower tendency to cause major bleeding compared to warfarin.
There are four distinct DOAC drugs available in the UK, the newest of which was introduced between 2008 and 2015. The study will make comparisons between the newest, edoxaban, and each of the other alternative DOAC treatments, as well as warfarin.
This study will determine whether the benefits of DOACs observed in clinical trials can be observed in routine UK clinical practice. Specifically, the study will examine each of the DOACs and Warfarin in newly treated patients and see how they compare with each other in terms of : 1) major bleeding rates, strokes, mortality; 2) treatment adherence and persistence.
AF, the commonest form of arrhythmia (1.5% prevalence), is characterized by irregular, rapid heartbeat increasing the risk of stroke (five times), heart failure, and death (two-fold). In the UK, a quarter of acute vascular events (the majority strokes) are AF-related incurring considerable human and healthcare costs.
AF treatment includes oral anticoagulation, preventing blood clotting, the main driver of the associated stroke risk. Warfarin, a VKA and the first line, requires careful dosage adjustment and regular blood tests to be used safely. Direct oral anticoagulant (DOACs), which are non-vitamin K antagonist, are easier to use and, in clinical trials, reduce stroke risk in AF patients and cause less major bleeding than warfarin.
Head-to-head efficacy and safety comparisons between the DOACs and warfarin using observational data have been made, though none from the UK.
Four distinct DOAC drugs are available in the UK, the newest of which was introduced between 2008 and 2015. The study will make new-user comparisons between the newest, edoxaban, and each of the other alternative treatments, as well as VKA warfarin by selecting propensity score (PS)-matched cohorts among anti-coagulant naïve patients with AF.
This study will determine the comparative effectiveness of each DOAC versus warfarin in routine UK clinical practice. Specifically, the study will assess whether in newly-treated patients and compared to warfarin, the use of each DOAC is associated with: 1) the rate of major bleeding, strokes, mortality; 2) treatment adherence and persistence.
Time-to-event analyses will use Cox proportional hazards regression, with censoring defined by either treatment switching, non-outcome related death, practice de-registration or database horizon. Generalized linear models will be constructed using the PS-matched cohorts to compare adherence and persistence between treatments. All multivariable models will be adjusted for baseline characteristics, including demography, comorbidities, and clinical status.
Major bleeding (primary) | systemic embolism | ischemic stroke | mortality | adherence and persistence |
Yasuyuki Matsushita - Chief Investigator - Daiichi Sankyo Co. Ltd. (Japan)
Rosa Wang - Corresponding Applicant - Daiichi Sankyo Co. Ltd. (Japan)
- Collaborator -
Allen Zhao - Collaborator - Not from an Organisation
Dong Dai - Collaborator - Daiichi Sankyo, Inc. (USA)
Michael DiFelice - Collaborator - Cobbs Creek Healthcare
Yichen Zhang - Collaborator - Cobbs Creek Healthcare
HES Admitted Patient Care;ONS Death Registration Data