Real-world utilization of and comparative outcomes arising from novel oral anticoagulants for atrial fibrillation and stroke prevention in the United Kingdom

Date of Approval: 
2020-07-29 00:00:00
Lay Summary: 
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 was mainly used however it requires careful dosage adjustment and regular blood tests to be used safely. Novel antagonist oral anticoagulant (NOACs) 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 NOAC 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 treatments, including warfarin. This study will determine whether the benefits of NOACs observed in clinical trials can be observed in routine UK clinical practice. Specifically, the study will compare each of the NOACs including Warfarin in newly treated patients and see how they compare with each other in terms of : 1) major bleeding rates (the primary outcome of interest), strokes, mortality; 2) treatment adherence and persistence; and 4) lower overall healthcare resource use and costs.
Technical Summary: 
Atrial fibrillation (AF), the commonest form of arrythmia (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, the first line, requires careful dosage adjustment and regular blood tests to be used safely. Novel antagonist oral anticoagulant (NOACs) 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 NOACs and warfarin using observational data have been made, though none from the UK. Four distinct NOAC drugs 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, including warfarin by selecting propensity score (PS)-matched cohorts among anti-coagulant naïve patients with AF. This study will determine the comparative effectiveness of each NOAC 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 NOAC is associated with: 1) the rate of major bleeding (the primary outcome of interest), strokes, mortality; 2) treatment adherence and persistence; and 4) lower overall healthcare resource use and costs. 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 HCRU (Poisson/binomial) and cost (gamma) between treatments. All multivariable models will be adjusted for baseline characteristics, including demography, comorbidities, and clinical status.
Health Outcomes to be Measured: 
Major bleeding (primary) | systemic embolism | ischaemic stroke | mortality | adherence and persistence | healthcare resource use and costs
Application Number: 
20_136
Collaborators: 

Craig Currie - Chief Investigator - Pharmatelligence Limited
Ellen Berni - Corresponding Applicant - Pharmatelligence Limited
Cindy Gao - Collaborator - Pharmerit International
Rosa Wang - Collaborator - Daiichi Sankyo
Sara Jenkins-Jones - Collaborator - Pharmatelligence Limited
Sue Beecroft - Collaborator - OPEN VIE ( Harvey Walsh Ltd )
Tracey Ellison - Collaborator - OPEN VIE ( Harvey Walsh Ltd )
Xiaocong Li Marston - Collaborator - Pharmerit International
Xin (Sam) Ye - Collaborator - Daiichi Sankyo
Yu-Chen Yeh - Collaborator - Pharmerit International

Linkages: 
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation